Patent Publication Number: US-2021172008-A1

Title: Methods and compositions to identify novel crispr systems

Description:
FIELD OF THE INVENTION 
     The invention is drawn to high throughput methods of discovery of genes useful for targeted genome editing. 
     REFERENCE TO A SEQUENCE LISTING SUBMITTED ELECTRONICALLY AS A TEXT FILE 
     The instant application contains a Sequence Listing which has been submitted electronically in ASCII format via EFS-Web and is hereby incorporated by reference in its entirety. Said ASCII copy, created on Mar. 29, 2019, is named L1034381010WO_0028_0_SL.txt, and is 41,946 bytes in size. 
     BACKGROUND OF THE INVENTION 
     Targeted genome editing or modification is rapidly becoming an important tool for basic and applied research, with clustered regularly interspaced short palindromic repeat (CRISPR) RNA-guided nucleases (RGNs) showing the most promise due to the ease of altering target specificity by engineering associated guide RNAs. Currently, only three CRISPR RGNs are available commercially and widely used in the literature:  Streptococcus pyogenes  Cas9,  Staphylococcus aureus  Cas9, and  Fransicella novicida  Cpf1. Given the diversity and abundance of microbial genomes, it is likely a large number of CRISPR RGNs have yet to be identified, many of which might exhibit alternate target recognition or improved activity over the three commercially available CRISPR RGNs. Complex samples containing mixed cultures of organisms often contain species that cannot be cultured or present other obstacles to performing traditional methods of gene discovery. Thus, a high throughput method of identifying new CRISPR RGN genes and systems, where up to millions of culturable and non-culturable microbes can be queried simultaneously would be advantageous. Newly identified RNA-guided nucleases can be used to edit genomes through the introduction of a sequence-specific, double-stranded break that is repaired via error-prone non-homologous end-joining (NHEJ) to introduce a mutation at a specific genomic location. Alternatively, heterologous DNA may be introduced into the genomic site via homology-directed repair. 
     BRIEF SUMMARY OF THE INVENTION 
     Compositions and methods for isolating new variants of known clustered regularly interspaced short palindromic repeats (CRISPR) RNA-guided nuclease (RGN) genes are provided. The provided compositions and methods are also useful in identifying a corresponding tracrRNA for new CRISPR RGN variants, and thus can be used to identify new CRISPR systems comprising an RGN and its associated guide RNA. The methods find use in identifying CRISPR RGN genes, and in some embodiments, CRISPR systems, in complex mixtures. Compositions comprise hybridization baits that hybridize to CRISPR RGN genes of interest, and in some embodiments flanking sequences, in order to selectively enrich the polynucleotides of interest from complex mixtures. Bait sequences may be specific for a number of distinct CRISPR RGN genes and may be designed to cover each CRISPR RGN gene of interest, and in some embodiments flanking sequences, by at least 2-fold. Thus, methods disclosed herein are drawn to an oligonucleotide hybridization gene capture approach for identification of new CRISPR RGN genes or CRISPR systems of interest from environmental samples. This approach bypasses the need for labor-intensive microbial strain isolation, permits simultaneous discovery of CRISPR RGN genes and CRISPR systems from multiple families of interest, and increases the potential to discover CRISPR RGN genes and CRISPR systems from low-abundance and unculturable organisms present in complex mixtures of environmental microbes. 
    
    
     DETAILED DESCRIPTION 
     Methods for identifying variants of known CRISPR RGN genes, and in some embodiments, their corresponding tracrRNAs, from complex mixtures are provided. The methods use labeled hybridization baits or bait sequences that correspond to a portion of known CRISPR RGN genes, and in some embodiments flanking sequences, to capture similar sequences from complex environmental samples. Once the DNA sequence is captured, subsequent sequencing and analysis can identify variants of the known CRISPR RGN genes and systems in a high throughput manner. 
     The methods of the invention are capable of identifying and isolating variants of known CRISPR RGN genes and CRISPR systems from a complex sample. By “complex sample” is intended any sample having DNA from more than one species of organism. In specific embodiments, the complex sample is an environmental sample, a biological sample, and/or a metagenomic sample. As used herein, the term “metagenome” or “metagenomic” refers to the collective genomes of all microorganisms present in a given habitat (Handelsman et al., (1998)  Chem. Biol.  5: R245-R249; Microbial Metagenomics, Metatranscriptomics, and Metaproteomics. Methods in Enzymology vol. 531 DeLong, ed. (2013)). Environmental samples can be from soil, rivers, ponds, lakes, industrial wastewater, seawater, forests, agricultural lands on which crops are growing or have grown, samples of plants or animals or other organisms associated with microorganisms that may be present within or without the tissues of the plant or animal or other organism, or any other source having biodiversity. In some embodiments, complex samples include metagenomics environmental samples that include the collective genomes of all microorganisms present in an environmental sample. Complex samples also include colonies or cultures of microorganisms that are grown, collected in bulk, and pooled for storage and DNA preparation. For example, colonies can be grown on plates, in bottles, or in other bulk containers and collected. In certain embodiments, complex samples are selected based on expected biodiversity that will allow for identification of variants of known CRISPR RGN genes and systems. In some embodiments, samples can be grown under conditions that allow for the growth of certain types of bacteria. For example, particular samples can be grown under either aerobic or anaerobic growth conditions or grown in media that selects for certain bacteria (e.g., methanol or high salt). Selection for certain species could include growth of environmental samples on defined carbon sources (for example, starch, mannitol, succinate or acetate), antibiotics (for example, cephalothin, vancomycin, polymyxin, kanamycin, neomycin, doxycycline, ampicillin, trimethoprim or sulfonamides), chromogenic substrates (for example, enzyme substrates such as phospholipase substrates, lecithinase substrates, cofactor metabolism substrates, nucleosidase substrates, glucosidase substrates, metalloprotease substrates and the like). 
     The methods disclosed herein do not require purified samples of single organisms but rather is able to identify novel CRISPR RGN genes and systems directly from uncharacterized mixes of populations of prokaryotic organisms: from soil, from crude samples, and samples that are collected and/or mixed and not subjected to any purification. In this manner, the methods described herein can identify CRISPR RGN genes and systems from unculturable organisms, or those organisms that are difficult to culture. 
     I. CRISPR Systems 
     The presently disclosed methods and compositions are useful for identifying novel CRISPR RGN genes and CRISPR systems. 
     Clustered regularly interspaced short palindromic repeats (CRISPRs) are found in bacterial and archaea genomes and comprise direct repeats interspaced by short segments of spacer DNA that were obtained from previous exposures to foreign DNA. These CRISPRs are transcribed and processed into CRISPR RNAs (crRNA), each of which comprises a CRISPR repeat sequence and a spacer sequence. A CRISPR array comprises an A-T rich leader sequence followed by the CRISPRs, CRISPR-associated system (cas) genes (including those encoding an RGN) and in some systems, a sequence encoding a trans-activating RNA (tracrRNA) within a particular genomic locus. 
     As used herein, a “CRISPR system” or “clustered regularly-interspaced short palindromic repeats system” comprises an RNA-guided nuclease (RGN) protein and a respective guide RNA that can bind to the RGN and direct the RGN to a target nucleotide sequence for cleavage. A CRISPR RNA-guided nuclease or RGN refers to a polypeptide that binds to a particular target nucleotide sequence in a sequence-specific manner and is directed to the target nucleotide sequence by a guide RNA molecule that is complexed with the polypeptide and hybridizes with the target nucleotide sequence. Generally, genomic sequences encoding RGNs are located near CRISPRs in the genome and thus are referred to herein as CRISPR RGNs. The RGN identified using the presently disclosed methods and compositions may be an endonuclease or an exonuclease. Although many native RNA-guided nucleases are capable of cleaving target nucleotide sequences upon binding, the presently disclosed methods and compositions can be used to identify RNA-guided nucleases that might be nuclease-dead (i.e., are capable of binding to, but not cleaving, a target nucleotide sequence). RNA-guided nucleases identified by the presently disclosed methods and compositions can cleave a target nucleotide sequence, resulting in a single- or double-stranded break. RNA-guided nucleases only capable of cleaving a single strand of a double-stranded nucleic acid molecule are referred to herein as nickases. 
     A target nucleotide sequence hybridizes with a guide RNA and is bound by an RNA-guided nuclease associated with the guide RNA. The target nucleotide sequence can then be subsequently cleaved by the RNA-guided nuclease if the protein possesses nuclease activity. The terms “cleave” or “cleavage” refer to the hydrolysis of at least one phosphodiester bond within the backbone of a target nucleotide sequence that can result in either single-stranded or double-stranded breaks within the target nucleotide sequence. A CRISPR RGN or system of interest or a CRISPR RGN or system identified using the presently disclosed methods and compositions can be capable of cleaving a target nucleotide sequence, resulting in staggered breaks or blunt ends. A CRISPR RGN or system of interest or a CRISPR RGN or system identified using the presently disclosed methods and compositions can target RNA or DNA, which can be single-stranded or double-stranded, or RNA:DNA hybrids. 
     A single organism can comprise multiple CRISPR systems of the same or different types. While the presently disclosed methods and compositions can be used to identify either Class 1 or Class 2 CRISPR systems, Class 2 CRISPR systems are of particular interest given that they comprise a single polypeptide with RGN activity. Class 1 systems, on the other hand, require a complex of proteins for nuclease activity. There are three known types of Class 2 CRISPR systems, Type II, Type V, and Type VI, among which there are multiple subtypes (subtype II-A, II-B, II-C, V-A, V-B, V-C, VI-A, VI-B, and VI-C, among other undefined or putative subtypes). Type II and Type V-B systems require tracrRNA, in addition to crRNA, for RGN activity. In general, Type V-A and VI only require a crRNA. All known Type II and Type V RGNs target double-stranded DNA, whereas all known Type VI RGNs target single-stranded RNA. 
     The term “guide RNA” refers to a nucleotide sequence having sufficient complementarity with a target nucleotide sequence to hybridize with the target sequence and direct sequence-specific binding of an associated RNA-guided nuclease to the target nucleotide sequence. Thus, a CRISPR RGN&#39;s respective guide RNA is one or more RNA molecules (generally, one or two), that can bind to the RGN and guide the RGN to bind to a particular target nucleotide sequence, and in those instances wherein the RGN has nickase or nuclease activity, also cleave the target nucleotide sequence. In some embodiments, the guide RNA comprises a CRISPR RNA (crRNA). In other embodiments, the guide RNA comprises both a crRNA and a trans-activating CRISPR RNA (tracrRNA). Native guide RNAs that comprise both a crRNA and a tracrRNA generally comprise two separate RNA molecules that hybridize to each other through the repeat sequence of the crRNA and the anti-repeat sequence of the tracrRNA. 
     Native direct repeat sequences within a CRISPR array generally range in length from 28 to 37 base pairs, although the length can vary between about 23 bp to about 55 bp. Spacer sequences within a CRISPR array generally range from about 32 to about 38 bp in length, although the length can be between about 21 bp to about 72 bp. Each CRISPR array generally comprises less than 50 units of the CRISPR repeat-spacer sequence. The CRISPRs are transcribed as part of a long transcript termed the primary CRISPR transcript, which comprises much of the CRISPR array. The primary CRISPR transcript is cleaved by cas proteins to produce crRNAs or in some cases, to produce pre-crRNAs that are further processed by additional cas proteins into mature crRNAs. Mature crRNAs comprise a spacer sequence and a CRISPR repeat sequence. In some embodiments in which pre-crRNAs are processed into mature crRNAs, maturation involves the removal of about one to about six or more 5′, 3′, or 5′ and 3′ nucleotides. For the purposes of genome editing or targeting a particular target nucleotide sequence of interest, these nucleotides that are removed during maturation of the pre-crRNA molecule are not necessary for generating or designing a guide RNA. 
     A CRISPR RNA (crRNA) comprises a spacer sequence and a CRISPR repeat sequence. The “spacer sequence” when referring to native crRNAs is the nucleotide sequence that directly hybridizes with a protospacer on a foreign DNA. A spacer sequence can also be engineered to be fully or partially complementary to a target nucleotide sequence of interest for the use of genome editing or targeting a particular genomic locus. The spacer sequence of engineered crRNAs can be about 8 to about 30 nucleotides in length, including about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, and about 30 nucleotides. In some embodiments, the spacer sequence of an engineered crRNA is about 10 to about 26 nucleotides in length, or about 12 to about 30 nucleotides in length. The CRISPR repeat sequence comprises a nucleotide sequence that comprises a region with sufficient complementarity to hybridize to a tracrRNA. The CRISPR repeat sequences of native mature crRNAs and engineered crRNAs can range in length from about 8 to about 30 nucleotides in length, including about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, and about 30 nucleotides. 
     In some systems, the CRISPR repeat sequence further comprises a region with secondary structure (e.g., stem-loop) or forms secondary structure upon hybridizing with its corresponding tracrRNA. Native coding sequences for crRNAs are generally on the opposite end of a CRISPR array from the RGN-encoding sequence. Given their distance from RGN-encoding sequences on CRISPR arrays, in some embodiments, the presently disclosed methods of using hybridization baits may not be successful in identifying crRNAs. The CRISPR repeat sequence, however, can be deduced after the identification of the anti-repeat in a CRISPR RGN&#39;s tracrRNA, as described elsewhere herein. 
     In those CRISPR systems that further comprise a tracrRNA, the native tracrRNA is transcribed from the CRISPR array. A tracrRNA molecule comprises a nucleotide sequence comprising a region that has sufficient complementarity to hybridize to a CRISPR repeat sequence, which is referred to herein as the anti-repeat region. In some systems, the tracrRNA molecule further comprises a region with secondary structure (e.g., stem-loop) or forms secondary structure upon hybridizing with its corresponding crRNA. In particular embodiments, the region of the tracrRNA that is fully or partially complementary to a CRISPR repeat sequence is at the 5′ end of the molecule and the 3′ end of the tracrRNA comprises secondary structure. This region of secondary structure generally comprises several hairpin structures, including the nexus hairpin, which is found adjacent to the anti-repeat sequence. The nexus hairpin often has a conserved nucleotide sequence in the base of the hairpin stem, with the motif UNANNC found in the majority of Type IIA nexus hairpins in tracrRNAs. There are often terminal hairpins at the 3′ end of the tracrRNA that can vary in structure and number, but often comprise a GC-rich Rho-independent transcriptional terminator hairpin followed by a string of U&#39;s at the 3′ end. See, for example, Briner et al. (2014)  Molecular Cell  56:333-339, Briner and Barrangou (2016)  Cold Spring Harb Protoc ; doi: 10.1101/pdb.top090902, and U.S. Publication No. 2017/0275648, each of which is herein incorporated by reference in its entirety. 
     Type IIA guide RNAs also comprise an upper stem, bulge, and lower stem that are created by base-pairing between the CRISPR repeat and the antirepeat of the tracrRNA. 
     In various embodiments, the anti-repeat region of the tracrRNA that is fully or partially complementary to the CRISPR repeat sequence comprises from about 8 nucleotides to more than about 30 nucleotides. For example, the region of base pairing between the tracrRNA sequence and the CRISPR repeat sequence can be about 8, about 9, about 10, about 11, about 12, about 13, about 14, about 15, about 16, about 17, about 18, about 19, about 20, about 21, about 22, about 23, about 24, about 25, about 26, about 27, about 28, about 29, about 30, or more nucleotides in length. In various embodiments, the entire tracrRNA can comprise from about 60 nucleotides to more than about 140 nucleotides. For example, the tracrRNA can be about 60, about 65, about 70, about 75, about 80, about 85, about 90, about 95, about 100, about 105, about 110, about 115, about 120, about 125, about 130, about 135, about 140, or more nucleotides in length. In particular embodiments, the tracrRNA is about 80 to about 90 nucleotides in length, including about 80, about 81, about 82, about 83, about 84, about 85, about 86, about 87, about 88, about 89, and about 90 nucleotides in length. 
     The bait sequences described herein can be designed to be complementary to flanking sequences of a known CRISPR RGN of interest such that the coding sequence for a tracrRNA, and thus, the tracrRNA, can be identified. 
     The sequence and structure of crRNAs and tracrRNAs is often specific for a particular CRISPR system. Thus, in order to identify a complete CRISPR system, the associated crRNA, and in some embodiments, tracrRNA must also be identified using the methods disclosed elsewhere herein or other methods known in the art. 
     The presently disclosed methods and compositions are useful for identifying variants of CRISPR RGN genes of interest. As used herein, the term “gene” refers to an open reading frame comprising a nucleotide sequence that encodes a polypeptide. In some embodiments, the methods and compositions are utilized to identify a complete CRISPR system (i.e., sequences encoding an RGN and a respective guide RNA, which can comprise both a tracrRNA and a crRNA or a crRNA only). 
     New variants of known CRISPR RGN genes and systems of interest can be identified using the methods disclosed herein. As used herein, a “CRISPR RGN gene or system of interest” is intended to refer to a known CRISPR RGN gene or system. Known CRISPR RGN genes or systems of interest that can be used in the methods and compositions disclosed herein include, but are not limited to, those listed in Table 1. The sequences and references provided herein are incorporated by reference. It is important to note that these CRISPR RGN genes are provided merely as examples; any CRISPR RGN genes can be used in the practice of the methods and compositions disclosed herein. 
     The methods disclosed herein can identify variants of known CRISPR RGNs or systems of interest. As used herein, the term “variant” can refer to homologs, orthologs, and paralogs. While the activity of a variant may be altered compared to the CRISPR RGN or system of interest, the variant should retain the functionality of the CRISPR RGN or system of interest. For example, a variant may have increased activity, decreased activity, a different spectrum of activity (e.g., nickase), a different specificity (e.g., altered PAM recognition) or any other alteration in activity when compared to the CRISPR RGN or system of interest. 
     In general, “variants” is intended to mean substantially similar sequences. For polynucleotides, a variant comprises a deletion and/or addition of one or more nucleotides at one or more internal sites within the native polynucleotide and/or a substitution of one or more nucleotides at one or more sites in the native polynucleotide. As used herein, a “native” or “wild type” polynucleotide or polypeptide comprises a naturally occurring nucleotide sequence or amino acid sequence, respectively. For polynucleotides, conservative variants include those sequences that, because of the degeneracy of the genetic code, encode the native amino acid sequence of the CRISPR gene of interest. Naturally occurring allelic variants such as these can be identified with the use of well-known molecular biology techniques, as, for example, with polymerase chain reaction (PCR) and hybridization techniques as outlined below. Variant polynucleotides also include synthetically derived polynucleotides, such as those generated, for example, by using site-directed mutagenesis but which still encode the polypeptide of the CRISPR gene of interest. Generally, variants of a particular polynucleotide disclosed herein will have at least about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity to that particular polynucleotide (e.g., a CRISPR RGN gene of interest) as determined by sequence alignment programs and parameters described elsewhere herein. 
     Variants of a particular polynucleotide disclosed herein (i.e., the reference polynucleotide) can also be evaluated by comparison of the percent sequence identity between the polypeptide encoded by a variant polynucleotide and the polypeptide encoded by the reference polynucleotide. Percent sequence identity between any two polypeptides can be calculated using sequence alignment programs and parameters described elsewhere herein. Where any given pair of polynucleotides disclosed herein is evaluated by comparison of the percent sequence identity shared by the two polypeptides they encode, the percent sequence identity between the two encoded polypeptides is at least about 40%, 45%, 50%, 55%, 60%, 65%, 70%, 75%, 80%, 85%, 90%, 91%, 92%, 93%, 94%, 95%, 96%, 97%, 98%, 99% or more sequence identity. 
     Some known CRISPR RGN genes and polypeptides exhibit relatively low sequence identity across the entire length of the sequences, although particular domains are more conserved. Thus, in some embodiments, the variants (genes or polypeptides) of known CRISPR RGN gene(s) or polypeptide(s) of interest discovered using the presently disclosed methods and compositions may have less than 95%, less than 90%, less than 85%, less than 80%, less than 75%, less than 70%, less than 65%, less than 60%, or less identity to the CRISPR RGN gene(s) or polypeptide(s) of interest. In certain embodiments, the variants (genes or polypeptides) of known CRISPR RGN gene(s) or polypeptide(s) of interest discovered using the presently disclosed methods and compositions may have between 60% and 95%, 65% and 95%, 70% and 95%, 75% and 95%, 80% and 95%, 85% and 95%, 90% and 95% identity to the CRISPR RGN gene(s) or polypeptide(s) of interest. 
     As used herein, “sequence identity” or “identity” in the context of two polynucleotides or polypeptide sequences makes reference to the residues in the two sequences that are the same when aligned for maximum correspondence over a specified comparison window. When percentage of sequence identity is used in reference to proteins it is recognized that residue positions which are not identical often differ by conservative amino acid substitutions, where amino acid residues are substituted for other amino acid residues with similar chemical properties (e.g., charge or hydrophobicity) and therefore do not change the functional properties of the molecule. When sequences differ in conservative substitutions, the percent sequence identity may be adjusted upwards to correct for the conservative nature of the substitution. Sequences that differ by such conservative substitutions are said to have “sequence similarity” or “similarity”. Means for making this adjustment are well known to those of skill in the art. Typically this involves scoring a conservative substitution as a partial rather than a full mismatch, thereby increasing the percentage sequence identity. Thus, for example, where an identical amino acid is given a score of 1 and a non-conservative substitution is given a score of zero, a conservative substitution is given a score between zero and 1. The scoring of conservative substitutions is calculated, e.g., as implemented in the program PC/GENE (Intelligenetics, Mountain View, Calif.). 
     As used herein, “percentage of sequence identity” means the value determined by comparing two optimally aligned sequences over a comparison window, wherein the portion of the polynucleotide sequence in the comparison window may comprise additions or deletions (i.e., gaps) as compared to the reference sequence (which does not comprise additions or deletions) for optimal alignment of the two sequences. The percentage is calculated by determining the number of positions at which the identical nucleic acid base or amino acid residue occurs in both sequences to yield the number of matched positions, dividing the number of matched positions by the total number of positions in the window of comparison, and multiplying the result by 100 to yield the percentage of sequence identity. 
     Unless otherwise stated, sequence identity/similarity values provided herein refer to the value obtained using GAP Version 10 using the following parameters: % identity and % similarity for a nucleotide sequence using GAP Weight of 50 and Length Weight of 3, and the nwsgapdna.cmp scoring matrix; % identity and % similarity for an amino acid sequence using GAP Weight of 8 and Length Weight of 2, and the BLOSUM62 scoring matrix; or any equivalent program thereof. By “equivalent program” is intended any sequence comparison program that, for any two sequences in question, generates an alignment having identical nucleotide or amino acid residue matches and an identical percent sequence identity when compared to the corresponding alignment generated by GAP Version 10. 
     The use of the term “polynucleotide” is not intended to limit the present disclosure to polynucleotides comprising DNA. Those of ordinary skill in the art will recognize that polynucleotides can comprise ribonucleotides (RNA) and combinations of ribonucleotides and deoxyribonucleotides. Such deoxyribonucleotides and ribonucleotides include both naturally occurring molecules and synthetic analogues. The polynucleotides disclosed herein also encompass all forms of sequences including, but not limited to, single-stranded forms, double-stranded forms, hairpins, stem-and-loop structures, and the like. 
     Two sequences are “optimally aligned” when they are aligned for similarity scoring using a defined amino acid substitution matrix (e.g., BLOSUM62), gap existence penalty and gap extension penalty so as to arrive at the highest score possible for that pair of sequences. Amino acid substitution matrices and their use in quantifying the similarity between two sequences are well-known in the art and described, e.g., in Dayhoff et al. (1978) “A model of evolutionary change in proteins.” In “Atlas of Protein Sequence and Structure,” Vol. 5, Suppl. 3 (ed. M. O. Dayhoff), pp. 345-352. Natl. Biomed. Res. Found., Washington, D.C. and Henikoff et al. (1992) Proc. Natl. Acad. Sci. USA 89:10915-10919. The BLOSUM62 matrix is often used as a default scoring substitution matrix in sequence alignment protocols. The gap existence penalty is imposed for the introduction of a single amino acid gap in one of the aligned sequences, and the gap extension penalty is imposed for each additional empty amino acid position inserted into an already opened gap. The alignment is defined by the amino acids positions of each sequence at which the alignment begins and ends, and optionally by the insertion of a gap or multiple gaps in one or both sequences, so as to arrive at the highest possible score. While optimal alignment and scoring can be accomplished manually, the process is facilitated by the use of a computer-implemented alignment algorithm, e.g., gapped BLAST 2.0, described in Altschul et al. (1997)  Nucleic Acids Res.  25:3389-3402, and made available to the public at the National Center for Biotechnology Information Website (www.ncbi.nlm.nih.gov). Optimal alignments, including multiple alignments, can be prepared using, e.g., PSI-BLAST, available through www.ncbi.nlm.nih.gov and described by Altschul et al. (1997)  Nucleic Acids Res.  25:3389-3402. 
     II. Bait Sequences 
     The methods and compositions described herein employ bait sequences to capture variants of CRISPR RGN genes or systems of interest from complex samples. As used herein a “bait sequence” or “bait” refers to a polynucleotide that hybridizes to a CRISPR RGN gene or system of interest, or variant thereof. In specific embodiments, bait sequences are single-stranded RNA sequences capable of hybridizing to a fragment of the CRISPR RGN gene or system of interest, or a variant thereof. For example, the RNA bait sequence can be complementary to the DNA sequence of a fragment of the CRISPR RGN gene or system of interest. In some embodiments, the bait sequence is capable of hybridizing to a fragment of the CRISPR RGN gene or system of interest that is at least 50, at least 70, at least 90, at least 100, at least 110, at least 120, at least 130, at least 140, at least 150, at least 170, at least 200, at least 250, at least 400, at least 1000 contiguous nucleotides, and up to the full-length polynucleotide sequence of the CRISPR RGN gene or system of interest. The baits can be contiguous or sequential RNA or DNA sequences. In one embodiment, bait sequences are RNA sequences. RNA sequences cannot self-anneal and work to drive the hybridization. 
     The bait sequence can be capable of hybridizing to a fragment of the CRISPR RGN gene of interest or a flanking region or a combination of both. A flanking region of a CRISPR RGN gene of interest comprises sequences that are 5′ (i.e., upstream), 3′ (i.e., downstream), or both 5′ and 3′ to the CRISPR RGN gene of interest of sufficient length to allow for the identification of a tracrRNA-coding sequence, which in turn, can be used to determine the tracrRNA sequence by determining the sequence encoded by the tracrRNA-coding sequence. In some embodiments, the flanking regions of a CRISPR RGN gene of interest to which bait sequences are designed are at least 50, at least 60, at least 70, at least 80, at least 90, at least 100, at least 110, at least 120, at least 130, at least 140, at least 150, at least 160, at least 170, at least 180, at least 190, at least 200, at least 210, at least 220, at least 230, at least 240, at least 250 nucleotides or more 5′, 3′ or both 5′ and 3′ from the CRISPR RGN gene of interest. In certain embodiments, the flanking regions of a CRISPR RGN gene of interest to which bait sequences are designed are about 100 to about 250 or about 150 to about 200 nucleotides 5′, 3′ or both 5′ and 3′ from the CRISPR RGN gene of interest. In specific embodiments, the flanking regions of a CRISPR RGN gene of interest to which bait sequences are designed are about 180 nucleotides 5′, 3′ or both 5′ and 3′ from the CRISPR RGN gene of interest. 
     In specific embodiments, baits are at least 50, at least 70, at least 90, at least 100, at least 110, at least 120, at least 130, at least 140, at least 150, at least 170, at least 200, or at least 250 contiguous polynucleotides. For example, the bait sequence can be 50-200 nt, 70-150 nt, 100-140 nt, or 110-130 nt in length. In particular embodiments, the bait comprises about 120 nucleotides. The baits can be labeled with any detectable label in order to detect and/or capture the first hybridization complex comprised of a bait sequence hybridized to a fragment of a variant of the CRISPR RGN gene of interest or flanking sequence, or a combination of both. In certain embodiments, the bait sequences are labeled with biotin, a hapten, or an affinity tag or the bait sequences are generated using biotinylated primers, e.g., where the baits are generated by nick-translation labeling of purified target organism DNA with biotinylated deoxynucleotides. In cases where the bait sequences are biotinylated, the target DNA can be captured using a binding partner (e.g., streptavidin molecule) attached to a solid phase. In specific embodiments, the baits are biotinylated RNA baits of about 120 nt in length. Alternatively, antibodies specific for the RNA-DNA hybrid can be used (see, for example, WO2013164319 A1). The baits may include adapter oligonucleotides suitable for PCR amplification, sequencing, or RNA transcription. The baits may include an RNA promoter or are RNA molecules prepared from DNA containing an RNA promoter (e.g., a T7 RNA promoter). The baits can be chemically synthesized or are alternatively transcribed from DNA templates in vitro or in vivo using any method known in the art. The baits can be isolated such that the bait pool is substantially or essentially free from chemical precursors, etc. The baits can be conjugated to a detectable label using any method known in the art. In particular embodiments, the baits are produced using Agilent SureSelect technology, or similar technology from NimbleGen (SeqCap EZ), Mycroarray (MYbaits), Integrated DNA Technologies (XGen), and LC Sciences (OligoMix). 
     In some embodiments, the bait pool comprises baits that are designed to 16S DNA sequences, or any other phylogenetically differential sequence, in order to capture sufficient portions of the 16S DNA to estimate the distribution of bacterial genera present in the sample. 
     The bait sequences span substantially the entire sequence of the known CRISPR RGN gene and in some embodiments, flanking sequences. In some embodiments, the bait sequences are overlapping bait sequences. As used herein, “overlapping bait sequences” or “overlapping” refers to fragments of the CRISPR RGN gene of interest and in some embodiments, flanking sequences that are represented in more than one bait sequence. For example, any given 120 nt segment of a CRISPR RGN gene of interest, and in some embodiments, flanking sequences can be represented by a bait sequence having a region complementary to nucleotides 1-60 of the fragment, another bait sequence having a region complementary to nucleotides 61-120 of the fragment, and a third bait sequence complementary to nucleotides 1-120. In some embodiments, at least 10, at least 30, at least 60, at least 90, or at least 120 nucleotides of each overlapping bait overlap with at least one other overlapping bait. In this manner, each nucleotide of a given CRISPR RGN gene of interest and in some embodiments, its flanking sequences, can be represented in at least 2 baits, which is referred to herein as being covered by at least 2× tiling. Accordingly, the method described herein can use baits or labeled baits described herein that cover any CRISPR RGN gene of interest, and in some embodiments, its flanking sequences, by at least 2× or at least 3× tiling. 
     Baits for multiple CRISPR RGN genes of interest, and in some embodiments flanking sequences, can be used concurrently to hybridize with sample DNA prepared from a complex mixture. For example, if a given complex sample is to be screened for variants of multiple CRISPR RGN genes or systems of interest, baits designed to each CRISPR RGN gene of interest, and in some embodiments, flanking sequences, can be combined in a bait pool prior to, or at the time of, mixing with prepared sample DNA. Accordingly, as used herein, a “bait pool” or “bait pools” refers to a mixture of baits designed to be specific for different fragments of an individual CRISPR RGN gene or system of interest and/or a mixture of baits designed to be specific for different CRISPR RGN genes or systems of interest. “Distinct baits” refers to baits that are designed to be specific for different, or distinct, fragments of CRISPR RGN genes or systems of interest. In some embodiments, a bait pool comprises at least 1,000, at least 5,000, at least 10,000, at least 20,000, at least 30,000, at least 40,000, at least 50,000 or more distinct baits. 
     Accordingly, in some embodiments, a method for preparing an RNA bait pool for the identification of CRISPR RGN genes or systems of interest is provided. The method comprises identifying overlapping fragments of a DNA sequence of at least one CRISPR RGN gene of interest, wherein the overlapping fragments span the entire DNA sequence of the CRISPR RGN gene of interest, and in some embodiments flanking sequences, and synthesizing RNA baits complementary to the DNA sequence fragments, labeling the RNA baits with a detectable label, and combining the labeled RNA baits to form the RNA bait pool. 
     A given RNA bait pool can be specific for at least 1, at least 2, at least 10, at least 50, at least 100, at least 150, at least 200, at least 250, at least 300, at least 500, at least 750, at least 800, at least 900, at least 1,000, at least 1,500, at least 3,000, at least 5,000, at least 10,000, at least 15,000, at least 20,000, at least 30,000, at least 40,000, at least 50,000, at least 55,000, at least 60,000, or any other number of CRISPR RGN genes or systems of interest. As used herein, a bait that is specific for a CRISPR RGN gene or system of interest is designed to hybridize to the CRISPR RGN gene of interest, or in some embodiments flanking sequences or a combination of both. A bait can be specific for more than one CRISPR RGN gene or system of interest. In specific embodiments, the sequences of the baits are designed to correspond to CRISPR RGN genes or systems of interest using software tools such as Nimble Design (NimbleGen; Roche). 
     III. Methods for Identifying Variants of CRISPR RGN Genes or Systems of Interest 
     Methods of the invention include preparation of bait sequences, preparation of complex mixture libraries, hybridization selection, sequencing, and analysis. Such methods are set forth in the experimental section in more detail. Additionally, see NucleoSpin® Soil User Manual, Rev. 03, U.S. Publication No. 20130230857; Gnirke et al. (2009) Nature Biotechnology 27:182-189; SureSelect XT  Target Enrichment System for Illumina Paired-End Sequencing Library Protocol, Version 1.6; NimbleGen SeqCap EZ Library SR User&#39;s Guide, Version 4.3; and NimbleGen SeqCap EZ Library LR User&#39;s Guide, Version 2.0, each of which is herein incorporated by reference in its entirety. 
     Methods of preparing complex samples include fractionation and extraction of environmental samples comprising soil, rivers, ponds, lakes, industrial wastewater, seawater, forests, agricultural lands on which crops are growing or have grown, or any other source having biodiversity. Fractionation can include filtration and/or centrifugation to preferentially isolate microorganisms. In some embodiments, complex samples are selected based on expected biodiversity that will allow for identification of CRISPR RGN genes or systems. Further methods of preparing complex samples include colonies or cultures of microorganisms that are grown, collected in bulk, and pooled for storage and DNA preparation. In certain embodiments, complex samples are subjected to heat treatment or pasteurization to enrich for microbial spores that are resistant to heating. In some embodiments, the colonies or cultures are grown in media that enrich for specific types of microbes or microbes having specific structural or functional properties, such as cell wall composition, resistance to an antibiotic or other compound, or ability to grow on a specific nutrient mix or specific compound as a source of an essential element, such as carbon, nitrogen, phosphorus, or potassium. 
     In order to provide sample DNA for hybridization to baits as described elsewhere herein, the sample DNA must be prepared for hybridization. Preparing DNA from a complex sample for hybridization refers to any process wherein DNA from the sample is extracted and reduced in size sufficient for hybridization, herein referred to as fragmentation. For example, DNA can be extracted from any complex sample directly, or by isolating individual organisms from the complex sample prior to DNA isolation. In some embodiments, sample DNA is isolated from a pure culture or a mixed culture of microorganisms. DNA can also be extracted directly from the environmental sample. DNA can be isolated by any method commonly known in the art for isolation of DNA from environmental or biological samples (see, e.g. Schneegurt et al. (2003) Current Issues in Molecular Biology 5:1-8; Zhou et al. (1996) Applied and Environmental Microbiology 62:316-322), including, but not limited to, the NucleoSpin Soil genomic DNA preparation kit (Macherey-Nagel GmbH &amp; Co., distributed in the US by Clontech). In one embodiment, extracted DNA can be enriched for any desired source of sample DNA. For example, extracted DNA can be enriched for prokaryotic DNA by amplification. As used herein, the term “enrich” or “enriched” refers to the process of increasing the concentration of a specific target DNA population. For example, DNA can be enriched by amplification, such as by PCR, such that the target DNA population is increased about 1.5-fold, about 2-fold, about 3-fold, about 5-fold, about 10-fold, about 15-fold, about 30-fold, about 50-fold, or about 100-fold. In certain embodiments, sample DNA is enriched by using 16S amplification. 
     In some embodiments, after DNA is extracted from a complex sample, the extracted DNA is prepared for hybridization by fragmentation (e.g., by shearing) and/or end-labeling. End-labeling can use any end labels that are suitable for indexing, sequencing, or PCR amplification of the DNA. The fragmented sample DNA may be about 100-1000, 100-500, 125-400, 150-300, 200-2000, 100-3000, at least 100, at least 150, at least 200, at least 250, at least 300, or about 350 nucleotides in length. The detectable label may be, for example, biotin, a hapten, or an affinity tag. Thus, in certain embodiments, sample DNA is sheared and the ends of the sheared DNA fragments are repaired to yield blunt-ended fragments with 5′-phosphorylated ends. Sample DNA can further have a 3′-dA overhang prior to ligation to indexing-specific adaptors. Such ligated DNA can be purified and amplified using PCR in order to yield the prepared sample DNA for hybridization. In other embodiments, the sample DNA is prepared for hybridization by shearing, adaptor ligation, amplification, and purification. 
     In some embodiments, RNA is prepared from complex samples. RNA isolated from complex samples contains genes expressed by the organisms or groups of organisms in a particular environment, which can have relevance to the physiological state of the organism(s) in that environment, and can provide information about what biochemical pathways are active in the particular environment (e.g. Booijink et al. 2010. Applied and Environmental Microbiology 76: 5533-5540). RNA so prepared can be reverse-transcribed into DNA for hybridization, amplification, and sequence analysis. 
     Baits can be mixed with prepared sample DNA prior to hybridization by any means known in the art. The amount of baits added to the sample DNA should be sufficient to bind fragments of a CRISPR gene or system of interest. In some embodiments, a greater amount of baits is added to the mixture compared to the amount of sample DNA. The ratio of bait to sample DNA for hybridization can be about 1:4, about 1:3, about 1:2, about 1:1.8, about 1:1.6, about 1:1.4, about 1:1.2, about 1:1, about 2:1, about 3:1, about 4:1, about 5:1, about 10:1, about 20:1, about 50:1, or about 100:1, and higher. 
     While hybridization conditions may vary, hybridization of such bait sequences may be carried out under stringent conditions. By “stringent conditions” or “stringent hybridization conditions” is intended conditions under which the bait will hybridize to its target sequence to a detectably greater degree than to other sequences (e.g., at least 2-fold over background). Stringent conditions are sequence-dependent and will be different in different circumstances. By controlling the stringency of the hybridization and/or washing conditions, target sequences that are 100% complementary to the bait can be identified (homologous probing). Alternatively, stringency conditions can be adjusted to allow some mismatching in sequences so that lower degrees of similarity are detected (heterologous probing). In specific embodiments, the prepared sample DNA is hybridized to the baits for 16-24 hours at about 45° C., about 50° C., about 55° C., about 60° C., about 65° C., about 70° C., or about 75° C. In particular embodiments, the prepared sample DNA is hybridized to the baits at about 65° C. 
     Typically, stringent conditions will be those in which the salt concentration is less than about 1.5 M Na ion, typically about 0.01 to 1.0 M Na ion concentration (or other salts) at pH 7.0 to 8.3, and the temperature is at least about 30° C. for short baits (e.g., 10 to 50 nucleotides) and at least about 60° C. for long baits (e.g., greater than 50 nucleotides). Stringent conditions may also be achieved with the addition of destabilizing agents such as formamide. Exemplary low stringency conditions include hybridization with a buffer solution of 30 to 35% formamide, 1 M NaCl, 1% SDS (sodium dodecyl sulfate) at 37° C., and a wash in 1× to 2×SSC (20×SSC=3.0 M NaCl/0.3 M trisodium citrate) at 50 to 55° C. Exemplary moderate stringency conditions include hybridization in 40 to 45% formamide, 1.0 M NaCl, 1% SDS at 37° C., and a wash in 0.5× to 1×SSC at 55 to 60° C. Exemplary high stringency conditions include hybridization in 50% formamide, 1 M NaCl, 1% SDS at 37° C., and a wash in 0.1×SSC at 60 to 65° C. Other exemplary high-stringency conditions are those found in SureSelect XT  Target Enrichment System for Illumina Paired-End Sequencing Library Protocol, Version 1.6 and NimbleGen SeqCap EZ Library SR User&#39;s Guide, Version 4.3. Optionally, wash buffers may comprise about 0.1% to about 1% SDS. Duration of hybridization is generally less than about 24 hours, usually about 4 to about 12 hours. The duration of the wash time will be at least a length of time sufficient to reach equilibrium. Specificity is typically the function of post-hybridization washes, the critical factors being the ionic strength and temperature of the final wash solution. For DNA-DNA hybrids, the Tm can be approximated from the equation of Meinkoth and Wahl (1984)  Anal. Biochem.  138:267-284: Tm=81.5° C.+16.6 (log M)+0.41 (% GC)−0.61 (% form)−500/L; where M is the molarity of monovalent cations, % GC is the percentage of guanosine and cytosine nucleotides in the DNA, % form is the percentage of formamide in the hybridization solution, and L is the length of the hybrid in base pairs. The Tm is the temperature (under defined ionic strength and pH) at which 50% of a complementary target sequence hybridizes to a perfectly matched bait. Tm is reduced by about 1° C. for each 1% of mismatching; thus, Tm, hybridization, and/or wash conditions can be adjusted to hybridize to sequences of the desired identity. For example, if sequences with &gt;90% identity are sought, the Tm can be decreased 10° C. Generally, stringent conditions are selected to be about 5° C. lower than the thermal melting point (Tm) for the specific sequence and its complement at a defined ionic strength and pH. However, severely stringent conditions can utilize a hybridization and/or wash at 1, 2, 3, or 4° C. lower than the thermal melting point (Tm); moderately stringent conditions can utilize a hybridization and/or wash at 6, 7, 8, 9, or 10° C. lower than the thermal melting point (Tm); low stringency conditions can utilize a hybridization and/or wash at 11, 12, 13, 14, 15, or 20° C. lower than the thermal melting point (Tm). Using the equation, hybridization and wash compositions, and desired Tm, those of ordinary skill will understand that variations in the stringency of hybridization and/or wash solutions are inherently described. If the desired degree of mismatching results in a Tm of less than 45° C. (aqueous solution) or 32° C. (formamide solution), it is optimal to increase the SSC concentration so that a higher temperature can be used. An extensive guide to the hybridization of nucleic acids is found in Tijssen (1993) Laboratory Techniques in Biochemistry and Molecular Biology—Hybridization with Nucleic Acid Probes, Part I, Chapter 2 (Elsevier, New York); and Ausubel et al., eds. (1995) Current Protocols in Molecular Biology, Chapter 2 (Greene Publishing and Wiley-Interscience, New York). See Sambrook et al. (1989) Molecular Cloning: A Laboratory Manual (2d ed., Cold Spring Harbor Laboratory Press, Plainview, N.Y.). 
     As used herein, a hybridization complex refers to sample DNA fragments hybridizing to a bait. Following hybridization, the labeled baits can be separated based on the presence of the detectable label, and the unbound sequences are removed under appropriate wash conditions that remove the nonspecifically bound DNA and unbound DNA, but do not substantially remove the DNA that hybridizes specifically. The hybridization complex can be captured and purified from non-binding baits and sample DNA fragments. For example, the hybridization complex can be captured by using a binding partner of the detectable label attached to the baits, wherein the binding partner is attached to a solid phase, such as a bead or a magnetic bead. The binding partner binds in a specific manner to the detectable label. For example, in those embodiments wherein the baits are biotinylated, the binding partner can be streptavidin. In such embodiments, the hybridization complex captured onto a streptavidin coated bead, for example, can be selected by magnetic bead selection. The captured sample DNA fragment can then be amplified and index tagged for multiplex sequencing. As used herein, “index tagging” refers to the addition of a known polynucleotide sequence in order to track the sequence or provide a template for PCR. Index tagging the captured sample DNA sequences can identify the DNA source in the case that multiple pools of captured and indexed DNA are sequenced together. As used herein, an “enrichment kit” or “enrichment kit for multiplex sequencing” refers to a kit designed with reagents and instructions for preparing DNA from a complex sample and hybridizing the prepared DNA with labeled baits. In certain embodiments, the enrichment kit further provides reagents and instructions for capture and purification of the hybridization complex and/or amplification of any captured fragments of the CRISPR RGN genes or systems of interest. In specific embodiments, the enrichment kit is the SureSelect XT  Target Enrichment System for Illumina Paired-End Sequencing Library Protocol, Version 1.6. In other specific embodiments, the enrichment kit is as described in the NimbleGen SeqCap EZ Library SR User&#39;s Guide, Version 4.3 Alternatively, the DNA from multiple complex samples can be indexed and amplified before hybridization. In such embodiments, the enrichment kit can be the SureSelect XT2  Target Enrichment System for Illumina Multiplexed Sequencing Protocol, Version D.0 
     Following hybridization, the captured target organism DNA can be sequenced by any means known in the art. Sequencing of nucleic acids isolated by the methods described herein is, in certain embodiments, carried out using massively parallel short-read sequencing systems such as those provided by Illumina®, Inc. (HiSeq 1000, HiSeq 2000, HiSeq 2500, Genome Analyzers, MiSeq systems), Applied Biosystems™ Life Technologies (ABI PRISM® Sequence detection systems, SOLiD™ System, Ion PGM™ Sequencer, Ion Proton™ Sequencer), because the read out generates more bases of sequence per sequencing unit than other sequencing methods that generate fewer but longer reads. Sequencing can also be carried out by methods generating longer reads, such as those provided by Oxford Nanopore Technologies® (GridiON, MiniON) or Pacific Biosciences (Pachio RS II), to provide a sequence read of the full length sequence of the variant of the CRISPR RGN gene or system of interest, in order to avoid assembling various shorter sequences. Sequencing can also be carried out by standard Sanger dideoxy terminator sequencing methods and devices, or on other sequencing instruments, further as those described in, for example, United States patents and U.S. Pat. Nos. 5,888,737, 6,175,002, 5,695,934, 6, 140,489, 5,863,722, 2007/007991, 2009/0247414, 2010/01 11768 and PCT application WO2007/123744 each of which is incorporated herein by reference in its entirety. 
     In some embodiments, sequences can be assembled by any means known in the art. The sequences of individual fragments of variants of CRISPR RGN genes or systems of interest can be assembled to identify the full length sequence of the variant of the CRISPR RGN gene or system of interest. In some embodiments, sequences are assembled using the CLC Bio suite of bioinformatics tools. Following assembly, sequences of variants of the CRISPR RGN genes or systems of interest are searched (e.g., sequence similarity search) against a database of known sequences including those of the CRISPR RGN genes or systems of interest in order to identify the variant of the CRISPR RGN gene or system of interest. In this manner, new variants (i.e., homologs) of CRISPR RGN genes and systems of interest can be identified from complex samples. 
     Given the low sequence identity between many CRISPR RGN genes, however, sequences of CRISPR RGN gene variants can also be analyzed for the presence of domains present in known CRISPR RGN genes, including but not limited to, RuvC domains, HNH domains, and PAM interacting domains. See, for example, Sapranauskas et al. (2011)  Nucleic Acids Res  39:9275-9282 and Nishimasu et al. (2014)  Cell  156(5):935-949, each of which is herein incorporated by reference in its entirety. The RuvC domain of  Streptococcus pyogenes  Cas9, for example, consists of a six-stranded mixed beta sheet flanked by alpha helices and two additional two-stranded antiparallel beta sheets and shares structural similarity with the retroviral integrase superfamily members characterized by an RNase H fold, such as  E. coli  RuvC (PDB code 1HJR) and  Thermus thermophilus  RuvC (PDB code 4LD0). RuvC nucleases have four catalytic residues (e.g., Asp10, Glu762, His983, and Asp986 in  S. pyogenes  Cas9) and cleave Holliday junctions. The HNH domain of  S. pyogenes  Cas9, for example, comprises a two-stranded antiparallel beta sheet flanked by four alpha helices and it shares structural similarity with the HNH endonucleases characterized by a ββα-metal fold, such as phage T4 endonuclease VII (PDB code 2QNC) and  Vibrio vulnificus  nuclease (PDB code 1OUP). HNH nucleases have three catalytic residues (e.g., Asp839, His 840, and Asn863 in  S. pyogenes  Cas9) and cleave nucleic acid substrates through a single-metal mechanism. The PAM-interacting domain of  S. pyogenes  Cas9 comprises residues 1099-1368, for example. 
     If a complete CRISPR system is desired, the flanking sequences of the variant of a CRISPR RGN gene of interest can be sequenced and analyzed to identify the tracrRNA-coding sequence, and thus, the tracrRNA sequence. One of ordinary skill in the art will appreciate that often tracrRNAs are encoded on the opposite coding strand from the RGN and often are within about 60 to about 100 nucleotides from the RGN-encoding sequence, either in the 5′ or 3′ direction. Methods for identifying the tracrRNA sequence include scanning the flanking sequences for a known antirepeat-coding sequence or a variant thereof. CRISPR repeat and antirepeat sequences utilized by known CRISPR RGNs are known in the art and can be found, for example, at the CRISPR database on the world wide web at crispr.i2bc.paris-saclay.fr/crispr/. Alternatively, a tracrRNA sequence can be identified by predicting the secondary structure of sequences encoding by the flanking sequences using any known computational method, including but not limited to NUPACK RNA folding software (Dirks et al. (2007)  SIAM Review  49(1):65-88, which is incorporated herein in its entirety), and searching for secondary structures similar to those described herein and outlined in Briner et al. (2014)  Molecular Cell  56:333-339, Briner and Barrangou (2016)  Cold Spring Harb Protoc ; doi: 10.1101/pdb.top090902, and U.S. Publication No. 2017/0275648 (each of which is incorporated herein by reference in its entirety), including but not limited to a nexus hairpin and a transcription-terminating hairpin. The CRISPR repeat sequence of the corresponding crRNA can then be deduced based on the identified anti-repeat sequence of the tracrRNA by generating a CRISPR repeat sequence that is fully or partially complementary to the anti-repeat sequence of the tracrRNA. The sequence of the remaining crRNA can be generated by incorporating functional modules seen in guide RNAs, including the lower stem, bulge, and upper stem. 
     In some embodiments, the method for identifying the tracrRNA-coding region and thus, the tracrRNA, comprises the development and use of Hidden Markov Models (HMMs) of RNA structures and sequences using previously published tracrRNAs (see, for example, Briner et al. (2014)  Molecular Cell  56:333-339, Briner and Barrangou (2016)  Cold Spring Harb Protoc ; doi: 10.1101/pdb.top090902, and U.S. Publication No. 2017/0275648, each of which is herein incorporated by reference in its entirety), as well as any previously identified tracrRNA sequences. 
     One of ordinary skill in the art will appreciate that for those CRISPR systems that are not expected to comprise a tracrRNA (e.g., Types V-A, VI), often the structure of the CRISPR repeat of the crRNA is more important than the actual sequence of the CRISPR repeat. Thus, various known crRNAs (or variants comprising similar structure) from known Type V-A or VI CRISPR RGNs can be paired with these types of CRISPR RGNs in order to obtain a complete CRISPR system. See, for example, Shmakov et al. (2015)  Mol Cell  60(3):385-397, which is herein incorporated by reference in its entirety. CRISPR systems that are not expected to comprise a tracrRNA are those that are identified using baits designed from known Type V-A or Type VI CRISPR systems or those that exhibit homology with these CRISPR systems. Alternatively, the inability to identify a tracrRNA in flanking sequences based on homology with known anti-repeat sequences or known tracrRNA secondary structures might indicate that the CRISPR system does not comprise a tracrRNA. 
     In some embodiments, the presently disclosed methods can further comprise a step of assaying for binding between the guideRNA and the newly identified CRISPR RGN. For these assays, a single guide RNA can be constructed in which both the crRNA and tracrRNA are comprised within a single RNA molecule. Generally, a linker sequence of at least 3 nucleotides separates the crRNA and tracrRNA on single guide RNAs. One of ordinary skill in the art will understand that the linker sequence should not comprise complementary bases in order to avoid the formation of a stem loop structure within or comprising the linker sequence. Alternatively, two distinct RNA molecules comprising the crRNA and the tracrRNA, respectively, can be used for this analysis, wherein the two RNA molecules are hybridized to one another through the CRISPR repeat sequence of the crRNA and the anti-repeat portion of the tracrRNA, which is referred to herein as a dual-guide RNA. For those CRISPR RGNs that are not expected to utilize a tracrRNA, the guide RNA comprises a single crRNA molecule. The single guide RNA, dual-guide RNA, or crRNA can be synthesized chemically or via in vitro transcription. 
     Assays for determining sequence-specific binding between a CRISPR RGN and a guide RNA are known in the art and include, but are not limited to, in vitro binding assays between an expressed CRISPR RGN and the guideRNA, which can be tagged with a detectable label (e.g., biotin) and used in a pull-down detection assay in which the guideRNA:CRISPR RGN complex is captured via the detectable label (e.g., with streptavidin beads). A control guideRNA with an unrelated sequence or structure to the guideRNA can be used as a negative control for non-specific binding of the CRISPR RGN to RNA. 
     In certain embodiments, if one wishes to use the identified CRISPR system for genome editing or for targeting a genomic location, the presently disclosed methods can further comprise steps wherein the preferred protospacer adjacent motif (PAM) sequence is identified for the novel CRISPR system. A protospacer adjacent motif is generally within about 1 to about 10 nucleotides from the target nucleotide sequence, including about 1, about 2, about 3, about 4, about 5, about 6, about 7, about 8, about 9, or about 10 nucleotides from the target nucleotide sequence. The PAM can be 5′ or 3′ of the target sequence. Generally, the PAM is a consensus sequence of about 3-4 nucleotides, but in particular embodiments, can be 2, 3, 4, 5, 6, 7, 8, 9, or more nucleotides in length. Methods for identifying a preferred PAM sequence or consensus sequence for a given CRISPR RGN are known in the art and include, but are not limited to the PAM depletion assay described by Karvelis et al. (2015)  Genome Biol  16:253, or the assay disclosed in Pattanayak et al. (2013)  Nat Biotechnol  31(9):839-43, each of which is incorporated by reference in its entirety. 
     The methods can further comprise a step of assaying for the ability of the identified CRISPR RGN, in association with its guideRNA, to bind to a target sequence and/or to cleave the target sequence in a sequence-specific manner. Methods to measure binding of a CRISPR RGN to a target sequence are known in the art and include chromatin immunoprecipitation assays, gel mobility shift assays, DNA pull-down assays, reporter assays, microplate capture and detection assays. Likewise, methods to measure cleavage or modification of a target sequence are known in the art and include in vitro or in vivo cleavage assays wherein cleavage is confirmed using PCR, sequencing, or gel electrophoresis, with or without the attachment of an appropriate label (e.g., radioisotope, fluorescent substance) to the target sequence to facilitate detection of degradation products. Alternatively, the nicking triggered exponential amplification reaction (NTEXPAR) assay can be used (see, e.g., Zhang et al. (2016)  Chem. Sci.  7:4951-4957). In vivo cleavage can be evaluated using the Surveyor assay (Guschin et al. (2010)  Methods Mol Biol  649:247-256). 
     In order to assay for the ability of the identified CRISPR RGN to bind to the guide RNA or to a target sequence and/or to cleave the target sequence in a sequence-specific manner, a polynucleotide encoding the identified CRISPR RGN can be expressed in an in vitro system or cellular system and can be purified using any method known in the art. 
     An “isolated” or “purified” polynucleotide or polypeptide, or biologically active portion thereof, is substantially or essentially free from components that normally accompany or interact with the polynucleotide or polypeptide as found in its naturally occurring environment. Thus, an isolated or purified polynucleotide or polypeptide is substantially free of other cellular material, or culture medium when produced by recombinant techniques, or substantially free of chemical precursors or other chemicals when chemically synthesized. A protein that is substantially free of cellular material includes preparations of protein having less than about 30%, 20%, 10%, 5%, or 1% (by dry weight) of contaminating protein. When the protein of the invention or biologically active portion thereof is recombinantly produced, optimally culture medium represents less than about 30%, 20%, 10%, 5%, or 1% (by dry weight) of chemical precursors or non-protein-of-interest chemicals. 
     The purified CRISPR RGN can be combined with its guide RNA in such a manner to allow for the formation of a ribonucleoprotein complex. Alternatively, a ribonucleoprotein complex comprising the identified CRISPR RGN can be purified from a cell or organism that has been transformed with polynucleotides that encode the RGN and a guide RNA and cultured under conditions that allow for the expression of the RGN polypeptide and guide RNA. The ribonucleoprotein complex can then be purified from a lysate of the cultured cells. 
     Methods for purifying an RGN polypeptide or RGN ribonucleoprotein complex from a lysate of a biological sample are known in the art (e.g., size exclusion and/or affinity chromatography, 2D-PAGE, HPLC, reversed-phase chromatography, immunoprecipitation). To enable purification, the identified CRISPR RGN can be fused to a purification tag (e.g., glutathione-S-transferase (GST), chitin binding protein (CBP), maltose binding protein, thioredoxin (TRX), poly(NANP), tandem affinity purification (TAP) tag, myc, AcV5, AU1, AUS, E, ECS, E2, FLAG, HA, nus, Softag 1, Softag 3, Strep, SBP, Glu-Glu, HSV, KT3, S, 51, T7, V5, VSV-G, 6×His, biotin carboxyl carrier protein (BCCP), and calmodulin). 
     IV. Kits for Identification of a Variant of a CRISPR RGN Gene or System of Interest 
     Kits are provided for identifying variants of CRISPR RGN genes or systems of interest by the methods disclosed herein. The kits include a bait pool or RNA bait pool, or reagents suitable for producing a bait pool specific for a CRISPR RGN gene or system of interest, along with other reagents, such as a solid phase containing a binding partner of any detectable label on the baits. In specific embodiments, the detectable label is biotin and the binding partner streptavidin or streptavidin adhered to magnetic beads. The kits may also include solutions for hybridization, washing, or eluting of the DNA/solid phase compositions described herein, or may include a concentrate of such solutions. 
     
       
         
           
               
             
               
                 TABLE 1 
               
             
            
               
                   
               
               
                 Exemplary CRISPR RGN genes of interest. 
               
            
           
           
               
               
               
               
               
               
               
            
               
                   
                   
                 NCBI 
                   
                   
                   
                   
               
               
                 Name 
                 Acc. No. 
                 Protein 
                 NCBI Nuc 
                 Authors 
                 Year 
                 Source Strain 
               
               
                   
               
            
           
           
               
               
               
               
               
               
               
            
               
                 Cas12a-1 
                 AWUR01000016.1 
                   
                 HMPREF1246_0236 
                 Shmakov et al 
                 2017 
                 Acidaminococcus_BV3L6_ 
               
               
                   
                   
                   
                   
                   
                   
                 BV3L6 
               
               
                 Cas12a-2 
                 KK211384.1 
                   
                 KK211384.1_16 
                 Shmakov et al 
                 2017 
                 Anaerovibrio_RM50_ 
               
               
                   
                   
                   
                   
                   
                   
                 RM50 
               
               
                 Cas12a-3 
                 JAIQ01000039.1 
                   
                 AA20_01655 
                 Shmakov et al 
                 2017 
                 Arcobacter_butzleri_L348 
               
               
                 Cas12a-4 
                 KQ959253.1 
                   
                 HMPREF1869_00137 
                 Shmakov et al 
                 2017 
                 Bacteroidales_bacterium_ 
               
               
                   
                   
                   
                   
                   
                   
                 KA00251_KA00251 
               
               
                 Cas12a-5 
                 GG774890.1 
                   
                 HMPREF0156_01430 
                 Shmakov et al 
                 2017 
                 Bacteroidetes_oral_taxon_ 
               
               
                   
                   
                   
                   
                   
                   
                 274_F0058 
               
               
                 Cas12a-6 
                 AUKC01000013.1 
                   
                 AUKC01000013.1_3 
                 Shmakov et al 
                 2017 
                 Butyrivibrio_NC3005_NC3005 
               
               
                 Cas12a-7 
                 AUKD01000009.1 
                   
                 AUKD01000009.1_66 
                 Shmakov et al 
                 2017 
                 Butyrivibrio_fibrisolvens_MD2001 
               
               
                 Cas12a-8 
                 CP001812.1 
                   
                 bpr_II405 
                 Shmakov et al 
                 2017 
                 Butyrivibrio_proteoclasticus_B316 
               
               
                 Cas12a-9 
                 LCAP01000004.1 
                   
                 UU43_C0004G0003 
                 Shmakov et al 
                 2017 
                 Candidatus_Falkowbacteria_ 
               
               
                   
                   
                   
                   
                   
                   
                 bacterium_GW2011_GWA2_41_14 
               
               
                 Cas12a-10 
                 CP004049.1 
                   
                 MMALV_08950 
                 Shmakov et al 
                 2017 
                 Candidatus_Methanomethylophilus_ 
               
               
                   
                   
                   
                   
                   
                   
                 alvus_Mx1201 
               
               
                 Cas12a-11 
                 CP010070.1 
                   
                 Mpt1_c09950 
                 Shmakov et al 
                 2017 
                 Candidatus_Methanoplasma_ 
               
               
                   
                   
                   
                   
                   
                   
                 termitum_MpT1 
               
               
                 Cas12a-12 
                 LBOO01000015.1 
                   
                 UR27_C0015G0004 
                 Shmakov et al 
                 2017 
                 Candidatus_Peregrinibacteria_ 
               
               
                   
                   
                   
                   
                   
                   
                 bacterium_GW2011_GWA2_33_10 
               
               
                 Cas12a-13 
                 LBOR01000010.1 
                   
                 UR30_C0010G0003 
                 Shmakov et al 
                 2017 
                 Candidatus_Peregrinibacteria_ 
               
               
                   
                   
                   
                   
                   
                   
                 bacterium_GW2011_GWC2_33_13 
               
               
                 Cas12a-14 
                 LBTJ01000016.1 
                   
                 US54_C00_16G0015 
                 Shmakov et al 
                 2017 
                 Candidatus_Roizmanbacteria_ 
               
               
                   
                   
                   
                   
                   
                   
                 bacterium_GW2011_GWA2_37_7 
               
               
                 Cas12a-15 
                 FR903162.1 
                   
                 BN720_00865 
                 Shmakov et al 
                 2017 
                 Eubacterium_CAG_581 
               
               
                 Cas12a-16 
                 FR902996.1 
                   
                 BN774_00378 
                 Shmakov et al 
                 2017 
                 Eubacterium_CAG_76 
               
               
                 Cas12a-17 
                 CP001104.1 
                   
                 EUBELI_01419 
                 Shmakov et al 
                 2017 
                 Eubacterium_eligens_ 
               
               
                   
                   
                   
                   
                   
                   
                 ATCC_27750 
               
               
                 Cas12a-18 
                 FR878942.1 
                   
                 BN765_00730 
                 Shmakov et al 
                 2017 
                 Eubacterium_eligens_CAG_72 
               
               
                 Cas12a-19 
                 JYGZ01000006.1 
                   
                 SY27_14115 
                 Shmakov et al 
                 2017 
                 Flavobacterium_316_316 
               
               
                 Cas12a-20 
                 FQ859183.1 
                   
                 FBFL15_2587 
                 Shmakov et al 
                 2017 
                 Flavobacterium_branchiophilum_ 
               
               
                   
                   
                   
                   
                   
                   
                 FL_15 
               
               
                 Cas12a-21 
                 CP002557.1 
                   
                 FNFX1_1431 
                 Shmakov et al 
                 2017 
                 Francisella_cf_novicida_Fx1 
               
               
                 Cas12a-22 
                 CP009444.1 
                   
                 LA02_1347 
                 Shmakov et al 
                 2017 
                 Francisella_philomiragia_ 
               
               
                   
                   
                   
                   
                   
                   
                 GA01_2801 
               
               
                 Cas12a-23 
                 CP009353.1 
                   
                 AS84_1114 
                 Shmakov et al 
                 2017 
                 Francisella_tularensis_ 
               
               
                   
                   
                   
                   
                   
                   
                 novicida_F6168 
               
               
                 Cas12a-24 
                 DS989819.1 
                   
                 FTE_0784 
                 Shmakov et al 
                 2017 
                 Francisella_tularensis_ 
               
               
                   
                   
                   
                   
                   
                   
                 novicida_FTE 
               
               
                 Cas12a-25 
                 DS995364.1 
                   
                 FTG_0873 
                 Shmakov et al 
                 2017 
                 Francisella_tularensis_ 
               
               
                   
                   
                   
                   
                   
                   
                 novicida_FTG 
               
               
                 Cas12a-26 
                 DS264129.1 
                   
                 FTCG_00909 
                 Shmakov et al 
                 2017 
                 Francisella_tularensis_novicida_ 
               
               
                   
                   
                   
                   
                   
                   
                 GA99_3549 
               
               
                 Cas12a-27 
                 KN046811.1 
                   
                 DR83_652 
                 Shmakov et al 
                 2017 
                 Francisella_tularensis_novicida 
               
               
                 Cas12a-28 
                 CP000439.1 
                   
                 FTN_1397 
                 Shmakov et al 
                 2017 
                 Francisella_tularensis_novicida_U112 
               
               
                 Cas12a-29 
                 CP009633.1 
                   
                 AW25_605 
                 Shmakov et al 
                 2017 
                 Francisella_tularensis_novicida_U112 
               
               
                 Cas12a-30 
                 CP010103.1 
                   
                 CH70_544 
                 Shmakov et al 
                 2017 
                 Francisella_tularensis_tularensis 
               
               
                 Cas12a-31 
                 LFLB01000034.1 
                   
                 LFLB01000034.1_7 
                 Shmakov et al 
                 2017 
                 Gammaproteobacteria_bacterium_ 
               
               
                   
                   
                   
                   
                   
                   
                 LS_SOB 
               
               
                 Cas12a-32 
                 JH601088.1 
                   
                 HMPREF9709_01099 
                 Shmakov et al 
                 2017 
                 Helcococcus_kunzii_ATCC_ 
               
               
                   
                   
                   
                   
                   
                   
                 51366 
               
               
                 Cas12a-33 
                 KE159629.1 
                   
                 C809_02517 
                 Shmakov et al 
                 2017 
                 Lachnospiraceae_bacterium_ 
               
               
                   
                   
                   
                   
                   
                   
                 COE1_COE1 
               
               
                 Cas12a-34 
                 JQKK01000008.1 
                   
                 JQKK01000008.1_137 
                 Shmakov et al 
                 2017 
                 Lachnospiraceae_bacterium_ 
               
               
                   
                   
                   
                   
                   
                   
                 MA2020_MA2020 
               
               
                 Cas12a-35 
                 KL370807.1 
                   
                 KL370807.1_38 
                 Shmakov et al 
                 2017 
                 Lachnospiraceae_bacterium_ 
               
               
                   
                   
                   
                   
                   
                   
                 MC2017_MC2017 
               
               
                 Cas12a-36 
                 KL370807.1 
                   
                 KL370807.1_39 
                 Shmakov et al 
                 2017 
                 Lachnospiraceae_bacterium_ 
               
               
                   
                   
                   
                   
                   
                   
                 MC2017_MC2017 
               
               
                 Cas12a-37 
                 JHWS01000001.1 
                   
                 JHWS01000001.1_302 
                 Shmakov et al 
                 2017 
                 Lachnospiraceae_bacterium_ 
               
               
                   
                   
                   
                   
                   
                   
                 NC2008_NC2008 
               
               
                 Cas12a-38 
                 JNKS01000011.1 
                   
                 JNKS01000011.1_50 
                 Shmakov et al 
                 2017 
                 Lachnospiraceae_bacterium_ 
               
               
                   
                   
                   
                   
                   
                   
                 ND2006_ND2006 
               
               
                 Cas12a-39 
                 AHMM02000017.1 
                   
                 LEP1GSC047_3100 
                 Shmakov et al 
                 2017 
                 Leptospira_inadai_Lyme_10 
               
               
                 Cas12a-40 
                 AOMT01000011.1 
                   
                 MBO_03467 
                 Shmakov et al 
                 2017 
                 Moraxella_bovoculi_237 
               
               
                 Cas12a-41 
                 KE384587.1 
                   
                 KE384587.1_6 
                 Shmakov et al 
                 2017 
                 Moraxella_caprae_DSM_19149 
               
               
                 Cas12a-42 
                 KE384190.1 
                   
                 KE384190.1_9 
                 Shmakov et al 
                 2017 
                 Oribacterium_NK2B42_ 
               
               
                   
                   
                   
                   
                   
                   
                 NK2B42 
               
               
                 Cas12a-43 
                 LCIC01000001.1 
                   
                 UW39_C0001G0044 
                 Shmakov et al 
                 2017 
                 Parcubacteria_group_bacterium_ 
               
               
                   
                   
                   
                   
                   
                   
                 GW2011_GWC2_44_17 
               
               
                 Cas12a-44 
                 LCID01000007.1 
                   
                 UW40_C0007G0006 
                 Shmakov et al 
                 2017 
                 Parcubacteria_group_bacterium_ 
               
               
                   
                   
                   
                   
                   
                   
                 GW2011_GWF2_44_17 
               
               
                 Cas12a-45 
                 JQJC01000021.1 
                   
                 HQ38_07045 
                 Shmakov et al 
                 2017 
                 Porphyromonas_crevioricanis_ 
               
               
                   
                   
                   
                   
                   
                   
                 COT_253_OH1447 
               
               
                 Cas12a-46 
                 JQJB01000003.1 
                   
                 HQ45_01350 
                 Shmakov et al 
                 2017 
                 Porphyromonas_crevioricanis_ 
               
               
                   
                   
                   
                   
                   
                   
                 COT_253_OH2125 
               
               
                 Cas12a-47 
                 BAOV01000052.1 
                   
                 PORCAN_2094 
                 Shmakov et al 
                 2017 
                 Porphyromonas_crevioricanis_ 
               
               
                   
                   
                   
                   
                   
                   
                 JCM_13913 
               
               
                 Cas12a-48 
                 BAOU01000008.1 
                   
                 PORCRE_269 
                 Shmakov et al 
                 2017 
                 Porphyromonas_crevioricanis_ 
               
               
                   
                   
                   
                   
                   
                   
                 JCM_15906 
               
               
                 Cas12a-49 
                 JRFB01000011.1 
                   
                 HR11_04570 
                 Shmakov et al 
                 2017 
                 Porphyromonas_macacae_ 
               
               
                   
                   
                   
                   
                   
                   
                 COT_192_OH2631 
               
               
                 Cas12a-50 
                 KB904124.1 
                   
                 KB904124.1_428 
                 Shmakov et al 
                 2017 
                 Porphyromonas_macacae_ 
               
               
                   
                   
                   
                   
                   
                   
                 DSM_20710_JCM_13914 
               
               
                 Cas12a-51 
                 BAKQ01000001.1 
                   
                 BAKQ01000001.1_129 
                 Shmakov et al 
                 2017 
                 Porphyromonas_macacae_ 
               
               
                   
                   
                   
                   
                   
                   
                 DSM_20710_JCM_13914 
               
               
                 Cas12a-52 
                 AUFP01000002.1 
                   
                 AUFP01000002.1_257 
                 Shmakov et al 
                 2017 
                 Prevotella_albensis_DSM_ 
               
               
                   
                   
                   
                   
                   
                   
                 11370_JCM_12258 
               
               
                 Cas12a-53 
                 BAJD01000001.1 
                   
                 BAJD01000001.1_53 
                 Shmakov et al 
                 2017 
                 Prevotella_albensis_ 
               
               
                   
                   
                   
                   
                   
                   
                 DSM_11370_JCM_12258 
               
               
                 Cas12a-54 
                 KK211334.1 
                   
                 KK211334.1_60 
                 Shmakov et al 
                 2017 
                 Prevotella_brevis_ATCC_19188 
               
               
                 Cas12a-55 
                 ADWO01000096.1 
                   
                 PBR_0786 
                 Shmakov et al 
                 2017 
                 Prevotella_bryantii_B14 
               
               
                 Cas12a-56 
                 JRNR01000108.1 
                   
                 HMPREF0654_09810 
                 Shmakov et al 
                 2017 
                 Prevotella_disiens_ 
               
               
                   
                   
                   
                   
                   
                   
                 DNF00882 
               
               
                 Cas12a-57 
                 AEDO01000031.1 
                   
                 HMPREF9296_0755 
                 Shmakov et al 
                 2017 
                 Prevotella_disiens_FB035_09AN 
               
               
                 Cas12a-58 
                 KE384028.1 
                   
                 KE384028.1_43 
                 Shmakov et al 
                 2017 
                 Proteocatella_sphenisci_DSM_23131 
               
               
                 Cas12a-59 
                 KE384121.1 
                   
                 KE384121.1_68 
                 Shmakov et al 
                 2017 
                 Pseudobutyrivibrio_ruminis_CF1b 
               
               
                 Cas12a-60 
                 JQDQ01000121.1 
                   
                 ER57_07115 
                 Shmakov et al 
                 2017 
                 Smithella_SCADC 
               
               
                 Cas12a-61 
                 JMED01000006.1 
                   
                 DS62_13820-2 
                 Shmakov et al 
                 2017 
                 Smithella_SC_K08D17 
               
               
                 Cas12a-62 
                 CP011280.1 
                   
                 VC03_02970 
                 Shmakov et al 
                 2017 
                 Sneathia_amnii_SN35 
               
               
                 Cas12a-63 
                 KL370853.1 
                   
                 KL370853.1_80 
                 Shmakov et al 
                 2017 
                 Succinivibrio_dextrinosolvens_H5 
               
               
                 Cas12a-64 
                 GL995220.1 
                   
                 GL995220.1_19 
                 Shmakov et al 
                 2017 
                 Succinivibrionaceae_bacterium_ 
               
               
                   
                   
                   
                   
                   
                   
                 WG_1_WG_1 
               
               
                 Cas12a-65 
                 JMKI01000031.1 
                   
                 EH55_04135 
                 Shmakov et al 
                 2017 
                 Synergistes_jonesii_78_1 
               
               
                 Cas12a-66 
                 LQBO01000001.1 
                   
                 AVO42_04040 
                 Shmakov et al 
                 2017 
                 Thiomicrospira_XS5_XS5 
               
               
                 Cas12a-67 
                 BBPX01000040.1 
                   
                 BBPX01000040.1_1 
                 Shmakov et al 
                 2017 
                 Treponema_endosymbiont_of_ 
               
               
                   
                   
                   
                   
                   
                   
                 Eucomonympha_D2 
               
               
                 Cas12a-68 
                 BBPY01000028.1 
                   
                 BBPY01000028.1_15 
                 Shmakov et al 
                 2017 
                 Treponema_endosymbiont_of_ 
               
               
                   
                   
                   
                   
                   
                   
                 Eucomonympha_E12 
               
               
                 Cas12a-69 
                 BBPZ01000036.1 
                   
                 BBPZ01000036.1_1 
                 Shmakov et al 
                 2017 
                 Treponema_endosymbiont_of_ 
               
               
                   
                   
                   
                   
                   
                   
                 Eucomonympha_E8 
               
               
                 Cas12a-70 
                 LBTH01000007.1 
                   
                 US52_C0007G0008 
                 Shmakov et al 
                 2017 
                 candidate_division_WS6_ 
               
               
                   
                   
                   
                   
                   
                   
                 bacterium_GW2011_GWA2_37_6 
               
               
                 Cas12a-71 
                 ADJS01008976 
                   
                 ADJS01008976_1 
                 Shmakov et al 
                 2017 
                 uncultured 
               
               
                 Cas12b-1 
                 BCQI01000053.1 
                   
                 BCQI01000053.1_4 
                 Shmakov et al 
                 2017 
                 Alicyclobacillus_acidiphilus_ 
               
               
                   
                   
                   
                   
                   
                   
                 NBRC_100859 
               
               
                 Cas12b-2 
                 AURB01000127.1 
                   
                 N007_06525 
                 Shmakov et al 
                 2017 
                 Alicyclobacillus_acidoterrestris_ 
               
               
                   
                   
                   
                   
                   
                   
                 ATCC_49025 
               
               
                 Cas12b-3 
                 KE386913.1 
                   
                 KE386913.1_1 
                 Shmakov et al 
                 2017 
                 Alicyclobacillus_contaminans_ 
               
               
                   
                   
                   
                   
                   
                   
                 DSM_17975 
               
               
                 Cas12b-4 
                 BCRP01000027.1 
                   
                 BCRP01000027.1_17 
                 Shmakov et al 
                 2017 
                 Alicyclobacillus_kakegawensis_ 
               
               
                   
                   
                   
                   
                   
                   
                 NBRC_103104 
               
               
                 Cas12b-5 
                 BCQV01000052.1 
                   
                 BCQV01000052.1_10 
                 Shmakov et al 
                 2017 
                 Alicyclobacillus_shizuokensis_ 
               
               
                   
                   
                   
                   
                   
                   
                 NBRC_103103 
               
               
                 Cas12b-6 
                 KI301973.1 
                   
                 KI301973.1_306 
                 Shmakov et al 
                 2017 
                 Bacillus_NSP2_1 
               
               
                 Cas12b-7 
                 JXLT01000152.1 
                   
                 B4166_3744 
                 Shmakov et al 
                 2017 
                 Bacillus_thermoamylovorans_ 
               
               
                   
                   
                   
                   
                   
                   
                 B4166 
               
               
                 Cas12b-8 
                 JXLU01000068.1 
                   
                 B4167_2499 
                 Shmakov et al 
                 2017 
                 Bacillus_thermoamylovorans_ 
               
               
                   
                   
                   
                   
                   
                   
                 B4167 
               
               
                 Cas12b-9 
                 AKKB01000053.1 
                   
                 PMI08_01933 
                 Shmakov et al 
                 2017 
                 Brevibacillus_CF112_CF112 
               
               
                 Cas12b-10 
                 AOBR01000150.1 
                   
                 D478_25088 
                 Shmakov et al 
                 2017 
                 Brevibacillus_agri_BAB_2500 
               
               
                 Cas12b-11 
                 AOBR01000150.1 
                   
                 D478_25093 
                 Shmakov et al 
                 2017 
                 Brevibacillus_agri_BAB_2500 
               
               
                 Cas12b-12 
                 LMXM01000006.1 
                   
                 LMXM01000006.1_115 
                 Shmakov et al 
                 2017 
                 Chloracidobacterium_ 
               
               
                   
                   
                   
                   
                   
                   
                 thermophilum_OC1 
               
               
                 Cas12b-13 
                 KE386988.1 
                   
                 KE386988.1_31 
                 Shmakov et al 
                 2017 
                 Desulfatirhabdium_butyrativorans_ 
               
               
                   
                   
                   
                   
                   
                   
                 DSM_18734 
               
               
                 Cas12b-14 
                 JPIK01000006.1 
                   
                 JPIK01000006.1_72 
                 Shmakov et al 
                 2017 
                 Desulfonatronum_thiodismutans_ 
               
               
                   
                   
                   
                   
                   
                   
                 MLF_1 
               
               
                 Cas12b-15 
                 KE386879.1 
                   
                 KE386879.1_222 
                 Shmakov et al 
                 2017 
                 Desulfovibrio_inopinatus_ 
               
               
                   
                   
                   
                   
                   
                   
                 DSM_10711 
               
               
                 Cas12b-16 
                 CP001349.1 
                   
                 Mnod_0560 
                 Shmakov et al 
                 2017 
                 Methylobacterium_nodulans_ 
               
               
                   
                   
                   
                   
                   
                   
                 ORS_2060 
               
               
                 Cas12b-17 
                 CP001349.1 
                   
                 Mnod_0561 
                 Shmakov et al 
                 2017 
                 Methylobacterium_nodulans_ 
               
               
                   
                   
                   
                   
                   
                   
                 ORS_2060 
               
               
                 Cas12b-18 
                 CP007053.1 
                   
                 OPIT5_03625 
                 Shmakov et al 
                 2017 
                 Opitutaceae_bacterium_ 
               
               
                   
                   
                   
                   
                   
                   
                 TAV5_TAV5 
               
               
                 Cas12b-19 
                 LNAA01000001.1 
                   
                 LNAA01000001.1_1060 
                 Shmakov et al 
                 2017 
                 Oscillatoriales_cyanobacterium_ 
               
               
                   
                   
                   
                   
                   
                   
                 MTP1_MTP1 
               
               
                 Cas12b-20 
                 KE387196.1 
                   
                 KE387196.1_31 
                 Shmakov et al 
                 2017 
                 Tuberibacillus_calidus_ 
               
               
                   
                   
                   
                   
                   
                   
                 DSM_17572 
               
               
                 Cas13a-1 
                 CVRQ01000008.1 
                   
                 T1815_05231 
                 Shmakov et al 
                 2017 
                 Agathobacter_rectalis_T1_815 
               
               
                 Cas13a-2 
                 JQLU01000005.1 
                   
                 JQLU01000005.1_155 
                 Shmakov et al 
                 2017 
                 Carnobacterium_gallinarum_ 
               
               
                   
                   
                   
                   
                   
                   
                 DSM_4847 
               
               
                 Cas13a-3 
                 JQLU0000005.1 
                   
                 JQLU01000005.1_2303 
                 Shmakov et al 
                 2017 
                 Carnobacterium_gallinarum_ 
               
               
                   
                   
                   
                   
                   
                   
                 DSM_4847 
               
               
                 Cas13a-4 
                 JONJ01000012.1 
                   
                 JONJ01000012.1_8 
                 Shmakov et al 
                 2017 
                 Clostridium_aminophilum_ 
               
               
                   
                   
                   
                   
                   
                   
                 DSM_10710 
               
               
                 Cas13a-5 
                 DS499551.1 
                   
                 EUBSIR_02687 
                 Shmakov et al 
                 2017 
                 Eubacterium_siraeum_DSM_15702 
               
               
                 Cas13a-6 
                 KB907524.1 
                   
                 KB907524.1_67 
                 Shmakov et al 
                 2017 
                 Eubacterium_siraeum_DSM_15702 
               
               
                 Cas13a-7 
                 CVTD020000026 
                   
                 CVTD020000026_43 
                 Shmakov et al 
                 2017 
                 Herbinix 
               
               
                 Cas13a-8 
                 JQKK01000015.1 
                   
                 JQKK01000015.1_80 
                 Shmakov et al 
                 2017 
                 Lachnospiraceae_bacterium_ 
               
               
                   
                   
                   
                   
                   
                   
                 MA2020_MA2020 
               
               
                 Cas13a-9 
                 AUJT01000030.1 
                   
                 AUJT01000030.1_16 
                 Shmakov et al 
                 2017 
                 Lachnospiraceae_bacterium_ 
               
               
                   
                   
                   
                   
                   
                   
                 NK4A144_NK4A144 
               
               
                 Cas13a-10 
                 ATWC01000054.1 
                   
                 ATWC01000054.1_6 
                 Shmakov et al 
                 2017 
                 Lachnospiraceae_bacterium_ 
               
               
                   
                   
                   
                   
                   
                   
                 NK4A179_NK4A179 
               
               
                 Cas13a-11 
                 CP001685.1 
                   
                 Lebu_1799 
                 Shmakov et al 
                 2017 
                 Leptotrichia_buccalis_C_1013_b 
               
               
                 Cas13a-12 
                 KI272904.1 
                   
                 HMPREF9108_01633 
                 Shmakov et al 
                 2017 
                 Leptotrichia_oral_taxon_ 
               
               
                   
                   
                   
                   
                   
                   
                 225_F0581 
               
               
                 Cas13a-13 
                 KI271320.1 
                   
                 HMPREF1552_00123 
                 Shmakov et al 
                 2017 
                 Leptotrichia_oral_taxon_ 
               
               
                   
                   
                   
                   
                   
                   
                 879_F0557 
               
               
                 Cas13a-14 
                 KB890278.1 
                   
                 KB890278.1_32 
                 Shmakov et al 
                 2017 
                 Leptotrichia_shahii_DSM_19757 
               
               
                 Cas13a-15 
                 KI271395.1 
                   
                 HMPREF9015_00520 
                 Shmakov et al 
                 2017 
                 Leptotrichia_wadei_F0279 
               
               
                 Cas13a-16 
                 KI271421.1 
                   
                 HMPREF9015_01858 
                 Shmakov et al 
                 2017 
                 Leptotrichia_wadei_F0279 
               
               
                 Cas13a-17 
                 KI271424.1 
                   
                 HMPREF9015_02301 
                 Shmakov et al 
                 2017 
                 Leptotrichia_wadei_F0279 
               
               
                 Cas13a-18 
                 JNFB01000012.1 
                   
                 EP58_05535 
                 Shmakov et al 
                 2017 
                 Listeria_newyorkensis_FSL_ 
               
               
                   
                   
                   
                   
                   
                   
                 M6_0635 
               
               
                 Cas13a-19 
                 FN557490.1 
                   
                 lse_1149 
                 Shmakov et al 
                 2017 
                 Listeria_seeligeri_1_2b_ 
               
               
                   
                   
                   
                   
                   
                   
                 SLCC3954 
               
               
                 Cas13a-20 
                 AODJ01000004.1 
                   
                 PWEIH_02614 
                 Shmakov et al 
                 2017 
                 Listeria_weihenstephanensis_ 
               
               
                   
                   
                   
                   
                   
                   
                 FSL_R9_0317 
               
               
                 Cas13a-21 
                 CP002345.1 
                   
                 Palpr_0179 
                 Shmakov et al 
                 2017 
                 Paludibacter_propionicigenes_WB4 
               
               
                 Cas13a-22 
                 AYPR01000020.1 
                   
                 U714_11360 
                 Shmakov et al 
                 2017 
                 Rhodobacter_capsulatus_DE442 
               
               
                 Cas13a-23 
                 AYQC01000019.1 
                   
                 U717_11515 
                 Shmakov et al 
                 2017 
                 Rhodobacter_capsulatus_R121 
               
               
                 Cas13a-24 
                 CP001312.1 
                   
                 RCAP_rcc02005 
                 Shmakov et al 
                 2017 
                 Rhodobacter_capsulatus_SB_1003 
               
               
                 Cas13a-25 
                 AYQB01000025.1 
                   
                 U715_11520 
                 Shmakov et al 
                 2017 
                 Rhodobacter_capsulatus_Y262 
               
               
                 Cas13a-26 
                 FR890758.1 
                   
                 BN714_01570 
                 Shmakov et al 
                 2017 
                 Ruminococcus_CAG_57 
               
               
                 Cas13a-27 
                 LARF01000048.1 
                   
                 LARF01000048.1_8 
                 Shmakov et al 
                 2017 
                 Ruminococcus_N15_MGS_57 
               
               
                 Cas13a-28 
                 HF545617.1 
                   
                 RBI_II00459 
                 Shmakov et al 
                 2017 
                 Ruminococcus_bicirculans_80_3 
               
               
                 Cas13a-29 
                 ACOK01000100.1 
                   
                 ACOK01000100.1_5 
                 Shmakov et al 
                 2017 
                 Ruminococcus_flavefaciens_FD_1 
               
               
                 Cas13a-30 
                 ADJS01008410 
                   
                 ADJS01008410_2 
                 Shmakov et al 
                 2017 
                 uncultured 
               
               
                 Cas13b-1 
                 JTLD01000029.1 
                   
                 JTLD01000029.1_31 
                 Shmakov et al 
                 2017 
                 Alistipes_Z0R0009_ZOR0009 
               
               
                 Cas13b-2 
                 CM001167.1 
                   
                 Bcop_1349-2 
                 Shmakov et al 
                 2017 
                 Bacteroides_coprosuis_DSM_18011 
               
               
                 Cas13b-3 
                 KE993153.1 
                   
                 HMPREF1981_03090 
                 Shmakov et al 
                 2017 
                 Bacteroides_pyogenes_F0041 
               
               
                 Cas13b-4 
                 BAIU01000001.1 
                   
                 JCM10003_349 
                 Shmakov et al 
                 2017 
                 Bacteroides_pyogenes_JCM_10003 
               
               
                 Cas13b-5 
                 JH932293.1 
                   
                 HMPREF9699_02005 
                 Shmakov et al 
                 2017 
                 Bergeyella_zoohelcum_ATCC_43767 
               
               
                 Cas13b-6 
                 CDOK01000028.1 
                   
                 CCAN11_1230002 
                 Shmakov et al 
                 2017 
                 Capnocytophaga_canimorsus_Cc11 
               
               
                 Cas13b-7 
                 CP002113.1 
                   
                 Ccan_11650 
                 Shmakov et al 
                 2017 
                 Capnocytophaga_canimorsus_Cc5 
               
               
                 Cas13b-8 
                 CDOD01000002.1 
                   
                 CCYN2B_100060 
                 Shmakov et al 
                 2017 
                 Capnocytophaga_cynodegmi_Ccyn2B 
               
               
                 Cas13b-9 
                 KN549099.1 
                   
                 KN549099.1_981 
                 Shmakov et al 
                 2017 
                 Chryseobacterium_YR477_YR477 
               
               
                 Cas13b-10 
                 JYGZ01000003.1 
                   
                 SY27_06350 
                 Shmakov et al 
                 2017 
                 Flavobacterium_316_316 
               
               
                 Cas13b-11 
                 FQ859183.1 
                   
                 FBFL15_2182 
                 Shmakov et al 
                 2017 
                 Flavobacterium_branchiophilum_ 
               
               
                   
                   
                   
                   
                   
                   
                 FL_15 
               
               
                 Cas13b-12 
                 CP013992.1 
                   
                 AWN65_03295 
                 Shmakov et al 
                 2017 
                 Flavobacterium_columnare_94_081 
               
               
                 Cas13b-13 
                 CP003222.2 
                   
                 FCOL_07235 
                 Shmakov et al 
                 2017 
                 Flavobacterium_columnare_ 
               
               
                   
                   
                   
                   
                   
                   
                 ATCC_49512 
               
               
                 Cas13b-14 
                 KE161016.1 
                   
                 HMPREF9712_03108 
                 Shmakov et al 
                 2017 
                 Myroides_odoratimimus_ 
               
               
                   
                   
                   
                   
                   
                   
                 CCUG_10230 
               
               
                 Cas13b-15 
                 JH590834.1 
                   
                 HMPREF9714_02132 
                 Shmakov et al 
                 2017 
                 Myroides_odoratimimus_ 
               
               
                   
                   
                   
                   
                   
                   
                 CCUG_12901 
               
               
                 Cas13b-16 
                 JH815535.1 
                   
                 HMPREF9711_00870 
                 Shmakov et al 
                 2017 
                 Myroides_odoratimimus_ 
               
               
                   
                   
                   
                   
                   
                   
                 CCUG_3837 
               
               
                 Cas13b-17 
                 CP013690.1 
                   
                 AS202_188_15 
                 Shmakov et al 
                 2017 
                 Myroides_odoratimimus_ 
               
               
                   
                   
                   
                   
                   
                   
                 PR63039 
               
               
                 Cas13b-18 
                 CP002345.1 
                   
                 Palpr_2606 
                 Shmakov et al 
                 2017 
                 Paludibacter_propionicigenes_WB4 
               
               
                 Cas13b-19 
                 JPOS010000l8.1 
                   
                 IX84_07840 
                 Shmakov et al 
                 2017 
                 Phaeodactylibacter_ 
               
               
                   
                   
                   
                   
                   
                   
                 xiamenensis_KD52 
               
               
                 Cas13b-20 
                 JQZY01000014.1 
                   
                 HQ50_05870 
                 Shmakov et al 
                 2017 
                 Porphyromonas_COT_052_ 
               
               
                   
                   
                   
                   
                   
                   
                 OH4946_COT_052_OH4946 
               
               
                 Cas13b-21 
                 CP012889.1 
                   
                 PGF_00012420 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_381 
               
               
                 Cas13b-22 
                 CP012889.1 
                   
                 PGF_00016090 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_381 
               
               
                 Cas13b-23 
                 CP011995.1 
                   
                 PGA7_00008170 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_A7436 
               
               
                 Cas13b-24 
                 CP011995.1 
                   
                 PGA7_00015700 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_A7436 
               
               
                 Cas13b-25 
                 CP013131.1 
                   
                 PGS_00015470 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_ 
               
               
                   
                   
                   
                   
                   
                   
                 A7A1_28 
               
               
                 Cas13b-26 
                 CP011996.1 
                   
                 PGJ_00015140 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_ 
               
               
                   
                   
                   
                   
                   
                   
                 AJW4 
               
               
                 Cas13b-27 
                 AP009380.1 
                   
                 PGN_1263 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_ 
               
               
                   
                   
                   
                   
                   
                   
                 ATCC_33277 
               
               
                 Cas13b-28 
                 AP009380.1 
                   
                 PGN_1623 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_ 
               
               
                   
                   
                   
                   
                   
                   
                 ATCC_33277 
               
               
                 Cas13b-29 
                 BCBV01000109.1 
                   
                 PGANDO_1674 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_ 
               
               
                   
                   
                   
                   
                   
                   
                 Ando 
               
               
                 Cas13b-30 
                 KI259867.1 
                   
                 HMPREF1988_02131 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_ 
               
               
                   
                   
                   
                   
                   
                   
                 F0185 
               
               
                 Cas13b-31 
                 KI259960.1 
                   
                 HMPREF1988_01768 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_ 
               
               
                   
                   
                   
                   
                   
                   
                 F0185 
               
               
                 Cas13b-32 
                 KI260014.1 
                   
                 HMPREF1989_02374 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_ 
               
               
                   
                   
                   
                   
                   
                   
                 F0566 
               
               
                 Cas13b-33 
                 KI258974.1 
                   
                 HMPREF1553_01900 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_ 
               
               
                   
                   
                   
                   
                   
                   
                 F0568 
               
               
                 Cas13b-34 
                 KI258981.1 
                   
                 HMPREF1553_02065 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_ 
               
               
                   
                   
                   
                   
                   
                   
                 F0568 
               
               
                 Cas13b-35 
                 KI259080.1 
                   
                 HMPREF1554_01647 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_F0569 
               
               
                 Cas13b-36 
                 KI259168.1 
                   
                 HMPREF1555_01119 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_F0570 
               
               
                 Cas13b-37 
                 KI259218.1 
                   
                 HMPREF1555_01956 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_F0570 
               
               
                 Cas13b-38 
                 CP007756.1 
                   
                 EG14_06045 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_HG66 
               
               
                 Cas13b-39 
                 CP007756.1 
                   
                 EG14_10345 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_HG66 
               
               
                 Cas13b-40 
                 CM001843.1 
                   
                 A343_1752 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_ 
               
               
                   
                   
                   
                   
                   
                   
                 JCVI_SC001 
               
               
                 Cas13b-41 
                 LOEL01000001.1 
                   
                 AT291_00385 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_MP4_504 
               
               
                 Cas13b-42 
                 LOEL01000010.1 
                   
                 AT291_05730 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_MP4504 
               
               
                 Cas13b-43 
                 KI629875.1 
                   
                 SJDPG2_03560 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_SJD2 
               
               
                 Cas13b-44 
                 AP012203.1 
                   
                 PGTDC60_1457 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_TDC60 
               
               
                 Cas13b-45 
                 KI260229.1 
                   
                 HMPREF1990_01280 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_W4087 
               
               
                 Cas13b-46 
                 KI260263.1 
                   
                 HMPREF1990_01800 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_W4087 
               
               
                 Cas13b-47 
                 AJZS01000011.1 
                   
                 HMPREF1322_1926 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_W50 
               
               
                 Cas13b-48 
                 AJZS01000051.1 
                   
                 HMPREF1322_2050 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_W50 
               
               
                 Cas13b-49 
                 AE015924.1 
                   
                 PG_0338 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_W83 
               
               
                 Cas13b-50 
                 AE015924.1 
                   
                 PG_1164 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gingivalis_W83 
               
               
                 Cas13b-51 
                 KN294104.1 
                   
                 HQ42_01095 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gulae_ 
               
               
                   
                   
                   
                   
                   
                   
                 COT_052_OH1355 
               
               
                 Cas13b-52 
                 JRAI01000002.1 
                   
                 HR08_00310 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gulae_ 
               
               
                   
                   
                   
                   
                   
                   
                 COT_052_OH1451 
               
               
                 Cas13b-53 
                 JRAJ01000010.1 
                   
                 HR09_05855 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gulae_ 
               
               
                   
                   
                   
                   
                   
                   
                 COT_052_OH2179 
               
               
                 Cas13b-54 
                 KQ040500.1 
                   
                 HR10_10685 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gulae_ 
               
               
                   
                   
                   
                   
                   
                   
                 COT_052_OH2199 
               
               
                 Cas13b-55 
                 JRFD01000046.1 
                   
                 HQ46_09365 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gulae_COT_ 
               
               
                   
                   
                   
                   
                   
                   
                 052_OH2857 
               
               
                 Cas13b-56 
                 JRAK01000129.1 
                   
                 HR15_09830 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gulae_COT_ 
               
               
                   
                   
                   
                   
                   
                   
                 052_OH3439 
               
               
                 Cas13b-57 
                 JRAQ01000019.1 
                   
                 HQ40_043025 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gulae_COT_ 
               
               
                   
                   
                   
                   
                   
                   
                 052_OH3471 
               
               
                 Cas13b-58 
                 KN300347.1 
                   
                 HR16_00525 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gulae_COT_ 
               
               
                   
                   
                   
                   
                   
                   
                 052_OH3498 
               
               
                 Cas13b-59 
                 JRAT01000012.1 
                   
                 HQ49_06245 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gulae_COT_ 
               
               
                   
                   
                   
                   
                   
                   
                 052_OH3856 
               
               
                 Cas13b-60 
                 JRAL01000022.1 
                   
                 HR17_04485 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gulae_COT_ 
               
               
                   
                   
                   
                   
                   
                   
                 052_OH4119 
               
               
                 Cas13b-61 
                 KB899147.1 
                   
                 KB899147.1_62 
                 Shmakov et al 
                 2017 
                 Porphyromonas_gulae_ 
               
               
                   
                   
                   
                   
                   
                   
                 DSM_15663 
               
               
                 Cas13b-62 
                 JHUW01000010.1 
                   
                 JHUW01000010.1_60 
                 Shmakov et al 
                 2017 
                 Prevotella_MA2016_ 
               
               
                   
                   
                   
                   
                   
                   
                 MA2016 
               
               
                 Cas13b-63 
                 ALJQ01000043.1 
                   
                 HMPREF1146_2324 
                 Shmakov et al 
                 2017 
                 Prevotella_MSX73_MSX73 
               
               
                 Cas13b-64 
                 JXQI01000021.1 
                   
                 ST42_02830 
                 Shmakov et al 
                 2017 
                 Prevotella_P4_76_P4_76 
               
               
                 Cas13b-65 
                 JXQK01000043.1 
                   
                 ST44_03600 
                 Shmakov et al 
                 2017 
                 Prevotella_P5_119_P5_119 
               
               
                 Cas13b-66 
                 JXQL01000055.1 
                   
                 ST45_06380 
                 Shmakov et al 
                 2017 
                 Prevotella_P5_125_P5_125 
               
               
                 Cas13b-67 
                 JXQJ01000080.1 
                   
                 ST43_06385 
                 Shmakov et al 
                 2017 
                 Prevotella_P5_60_P5_60 
               
               
                 Cas13b-68 
                 BAKF01000019.1 
                   
                 BAKF01000019.1_53 
                 Shmakov et al 
                 2017 
                 Prevotella_aurantiaca_JCM_15754 
               
               
                 Cas13b-69 
                 GL586311.1 
                   
                 HMPREF6485_0083 
                 Shmakov et al 
                 2017 
                 Prevotella_buccae_ATCC_33574 
               
               
                 Cas13b-70 
                 GG739967.1 
                   
                 HMPREF0649_02461 
                 Shmakov et al 
                 2017 
                 Prevotella_buccae_D17 
               
               
                 Cas13b-71 
                 JVYX01000689.1 
                   
                 JVYX01000689.1_4 
                 Shmakov et al 
                 2017 
                 Prevotella_denticola_1205_PDEN 
               
               
                 Cas13b-72 
                 JVYX01000736.1 
                   
                 JVYX01000736.1_6 
                 Shmakov et al 
                 2017 
                 Prevotella_denticola_1205_PDEN 
               
               
                 Cas13b-73 
                 JVYU01002440.1 
                   
                 JVYU01002440.1_2 
                 Shmakov et al 
                 2017 
                 Prevotella_denticola_1208_PDEN 
               
               
                 Cas13b-74 
                 BAJY01000004.1 
                   
                 BAJY01000004.1_86 
                 Shmakov et al 
                 2017 
                 Prevotella_falsenii_DSM_ 
               
               
                   
                   
                   
                   
                   
                   
                 22864_JCM_15124 
               
               
                 Cas13b-75 
                 AP014926.1 
                   
                 PI172_2270 
                 Shmakov et al 
                 2017 
                 Prevotella_intermedia_17_2 
               
               
                 Cas13b-76 
                 CP003502.1 
                   
                 PIN17_0200 
                 Shmakov et al 
                 2017 
                 Prevotella_intermedia_17 
               
               
                 Cas13b-77 
                 KE392225.1 
                   
                 KE392225.1_46 
                 Shmakov et al 
                 2017 
                 Prevotella_intermedia_ATCC_ 
               
               
                   
                   
                   
                   
                   
                   
                 25611_DSM_20706 
               
               
                 Cas13b-78 
                 JAEZ01000017.1 
                   
                 JAEZ01000017.1_46 
                 Shmakov et al 
                 2017 
                 Prevotella_intermedia_ATCC_ 
               
               
                   
                   
                   
                   
                   
                   
                 25611_DSM_20706 
               
               
                 Cas13b-79 
                 ATMK01000017.1 
                   
                 M573_117042 
                 Shmakov et al 
                 2017 
                 Prevotella_intermedia_ZT 
               
               
                 Cas13b-80 
                 GL982513.1 
                   
                 HMPREF9144_1146 
                 Shmakov et al 
                 2017 
                 Prevotella_pallens_ATCC_700821 
               
               
                 Cas13b-81 
                 AWET01000045.1 
                   
                 HMPREF1218_0639 
                 Shmakov et al 
                 2017 
                 Prevotella_pleuritidis_F0068 
               
               
                 Cas13b-82 
                 BAJN01000005.1 
                   
                 BAJN01000005.1_116 
                 Shmakov et al 
                 2017 
                 Prevotella_pleuritidis_JCM_14110 
               
               
                 Cas13b-83 
                 KB291002.1 
                   
                 HMPREF9151_01387 
                 Shmakov et al 
                 2017 
                 Prevotella_saccharolytica_F0055 
               
               
                 Cas13b-84 
                 BAKN01000001.1 
                   
                 BAKN01000001.1_231 
                 Shmakov et al 
                 2017 
                 Prevotella_saccharolytica_JCM_17484 
               
               
                 Cas13b-85 
                 CP003879.1 
                   
                 P700755_002426-2 
                 Shmakov et al 
                 2017 
                 Psychroflexus_torquis_ 
               
               
                   
                   
                   
                   
                   
                   
                 ATCC_700755 
               
               
                 Cas13b-86 
                 CP007504.1 
                   
                 CG09_1718 
                 Shmakov et al 
                 2017 
                 Riemerella_anatipestifer_153 
               
               
                 Cas13b-87 
                 CP007503.1 
                   
                 CG08_1741 
                 Shmakov et al 
                 2017 
                 Riemerella_anatipestifer_17 
               
               
                 Cas13b-88 
                 CP002346.1 
                   
                 Riean_1551 
                 Shmakov et al 
                 2017 
                 Riemerella_anatipestifer_ATCC_ 
               
               
                   
                   
                   
                   
                   
                   
                 11845_DSM_15868 
               
               
                 Cas13b-89 
                 CP003388.1 
                   
                 RA0C_1842 
                 Shmakov et al 
                 2017 
                 Riemerella_anatipestifer_ 
               
               
                   
                   
                   
                   
                   
                   
                 ATCC_11845_DSM_15868 
               
               
                 Cas13b-90 
                 CP004020.1 
                   
                 G148_2040 
                 Shmakov et al 
                 2017 
                 Riemerella_anatipestifer_RA_CH_2 
               
               
                 Cas13b-91 
                 CP002562.1 
                   
                 RIA_0639 
                 Shmakov et al 
                 2017 
                 Riemerella_anatipestifer_RA_GD 
               
               
                 Cas13b-92 
                 KB206042.1 
                   
                 KB206042.1_12 
                 Shmakov et al 
                 2017 
                 Riemerella_anatipestifer_RA_SG 
               
               
                 Cas13b-93 
                 AENH01000026.1 
                   
                 RAYM_05191 
                 Shmakov et al 
                 2017 
                 Riemerella_anatipestifer_RA_YM 
               
               
                 Cas13b-94 
                 CP007204.1 
                   
                 AS87_08290 
                 Shmakov et al 
                 2017 
                 Riemerella_anatipestifer_Yb2 
               
               
                 Cas13c-1 
                 CCEZ01000008.1 
                   
                 CCEZ01000008.1_165 
                 Shmakov et al 
                 2017 
                 Anaerosalibacter_ND1 
               
               
                 Cas13c-2 
                 JTLI01000096.1 
                   
                 JTLI01000096.1_1 
                 Shmakov et al 
                 2017 
                 Cetobacterium_ZOR0034_ZOR0034 
               
               
                 Cas13c-3 
                 JAAH01000065.1 
                   
                 FUSO8_06265 
                 Shmakov et al 
                 2017 
                 Fusobacterium_necrophorum_DJ_2 
               
               
                 Cas13c-4 
                 JH590847.1 
                   
                 HMPREF9466_01873 
                 Shmakov et al 
                 2017 
                 Fusobacterium_necrophorum_ 
               
               
                   
                   
                   
                   
                   
                   
                 funduliforme_1_1_36S 
               
               
                 Cas13c-5 
                 AJSY01000032.1 
                   
                 HMPREF1049_0423 
                 Shmakov et al 
                 2017 
                 Fusobacterium_necrophorum_ 
               
               
                   
                   
                   
                   
                   
                   
                 funduliforme_ATCC_51357 
               
               
                 Cas13c-6 
                 JHXW01000011.1 
                   
                 JHXW01000011.1_54 
                 Shmakov et al 
                 2017 
                 Fusobacterium_perfoetens_ 
               
               
                   
                   
                   
                   
                   
                   
                 ATCC_29250 
               
               
                 Cas9-1 
                 NC_016077 
                 352684361 
                   
                 Makarova et al 
                 2015 
                 Acidaminococcus_intestini_ 
               
               
                   
                   
                   
                   
                   
                   
                 RyC_MR95_uid74445 
               
               
                 Cas9-2 
                 NC_008578 
                 117929158 
                   
                 Makarova et al 
                 2015 
                 Acidothermus_cellulolyticus_ 
               
               
                   
                   
                   
                   
                   
                   
                 11B_uid58501 
               
               
                 Cas9-3 
                 NC_015138 
                 326315085 
                   
                 Makarova et al 
                 2015 
                 Acidovorax_avenae_ATCC_ 
               
               
                   
                   
                   
                   
                   
                   
                 19860_uid42497 
               
               
                 Cas9-4 
                 NC_011992 
                 222109285 
                   
                 Makarova et al 
                 2015 
                 Acidovorax_ebreus_TPSY_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid59233 
               
               
                 Cas9-5 
                 NC_009655 
                 152978060 
                   
                 Makarova et al 
                 2015 
                 Actinobacillus_succinogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 130Z_uid58247 
               
               
                 Cas9-6 
                 NC_018690 
                 407692091 
                   
                 Makarova et al 
                 2015 
                 Actinobacillus_suis_H91_ 
               
               
                   
                   
                   
                   
                   
                   
                 0380_uid_176363 
               
               
                 Cas9-7 
                 NC_010655 
                 187736489 
                   
                 Makarova et al 
                 2015 
                 Akkermansia_muciniphila_ 
               
               
                   
                   
                   
                   
                   
                   
                 ATCC_BAA_835_uid58985 
               
               
                 Cas9-8 
                 NC_014910 
                 319760940 
                   
                 Makarova et al 
                 2015 
                 Alicycliphilus_denitrificans_ 
               
               
                   
                   
                   
                   
                   
                   
                 BC_uid49953 
               
               
                 Cas9-9 
                 NC_015422 
                 330822845 
                   
                 Makarova et al 
                 2015 
                 Alicycliphilus_denitrificans_ 
               
               
                   
                   
                   
                   
                   
                   
                 K601_uid66307 
               
               
                 Cas9-10 
                 NC_013854 
                 288957741 
                   
                 Makarova et al 
                 2015 
                 Azospirillum_B510_uid46085 
               
               
                 Cas9-11 
                 NC_022526 
                 549484339 
                   
                 Makarova et al 
                 2015 
                 Bacteroides_CF50_uid222805 
               
               
                 Cas9-12 
                 NC_016776 
                 375360193 
                   
                 Makarova et al 
                 2015 
                 Bacteroides_fragilis_638R_uid84217 
               
               
                 Cas9-13 
                 NC_003228 
                 60683389 
                   
                 Makarova et al 
                 2015 
                 Bacteroides_fragilis_NCTC_ 
               
               
                   
                   
                   
                   
                   
                   
                 9343_uid57639 
               
               
                 Cas9-14 
                 NC_020813 
                 471261880 
                   
                 Makarova et al 
                 2015 
                 Bdellovibrio_exovorus_JSS_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid194119 
               
               
                 Cas9-15 
                 NC_018010 
                 390944707 
                   
                 Makarova et al 
                 2015 
                 Belliella_baltica_DSM_ 
               
               
                   
                   
                   
                   
                   
                   
                 15883_uid168182 
               
               
                 Cas9-16 
                 NC_020515 
                 470166767 
                   
                 Makarova et al 
                 2015 
                 Bibersteinia_trehalosi_192_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid193709 
               
               
                 Cas9-17 
                 NC_014616 
                 310286728 
                   
                 Makarova et al 
                 2015 
                 Bifidobacterium_bifidum_S17_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid59545 
               
               
                 Cas9-18 
                 NC_013714 
                 283456135 
                   
                 Makarova et al 
                 2015 
                 Bifidobacterium_dentium_ 
               
               
                   
                   
                   
                   
                   
                   
                 Bd1_uid43091 
               
               
                 Cas9-19 
                 NC_010816 
                 189440764 
                   
                 Makarova et al 
                 2015 
                 Bifidobacterium_longum_ 
               
               
                   
                   
                   
                   
                   
                   
                 DJO10A_uid58833 
               
               
                 Cas9-20 
                 NC_017221 
                 384200944 
                   
                 Makarova et al 
                 2015 
                 Bifidobacterium_longum_ 
               
               
                   
                   
                   
                   
                   
                   
                 KACC_91563_uid_158861 
               
               
                 Cas9-21 
                 NC_021031 
                 479188345 
                   
                 Makarova et al 
                 2015 
                 Butyrivibrio_fibrisolvens_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid197155 
               
               
                 Cas9-22 
                 NC_022362 
                 544063172 
                   
                 Makarova et al 
                 2015 
                 Campylobacter_jejuni_00_ 
               
               
                   
                   
                   
                   
                   
                   
                 2425_uid219359 
               
               
                 Cas9-23 
                 NC_022352 
                 543948719 
                   
                 Makarova et al 
                 2015 
                 Campylobacter_jejuni_00_ 
               
               
                   
                   
                   
                   
                   
                   
                 2426_uid219324 
               
               
                 Cas9-24 
                 NC_022351 
                 543946932 
                   
                 Makarova et al 
                 2015 
                 Campylobacter_jejuni_00_ 
               
               
                   
                   
                   
                   
                   
                   
                 2538_uid219325 
               
               
                 Cas9-25 
                 NC_022353 
                 543950499 
                   
                 Makarova et al 
                 2015 
                 Campylobacter_jejuni_00_ 
               
               
                   
                   
                   
                   
                   
                   
                 2544_uid219326 
               
               
                 Cas9-26 
                 NC_022529 
                 549693479 
                   
                 Makarova et al 
                 2015 
                 Campylobacter_jejuni_4031_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid222817 
               
               
                 Cas9-27 
                 NC_009839 
                 157415744 
                   
                 Makarova et al 
                 2015 
                 Campylobacter_jejuni_81116_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid58771 
               
               
                 Cas9-28 
                 NC_017279 
                 384448746 
                   
                 Makarova et al 
                 2015 
                 Campylobacter_jejuni_IA3902_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid159531 
               
               
                 Cas9-29 
                 NC_017280 
                 384442102 
                   
                 Makarova et al 
                 2015 
                 Campylobacter_jejuni_M1_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid159535 
               
               
                 Cas9-30 
                 NC_017280 
                 384442103 
                   
                 Makarova et al 
                 2015 
                 Campylobacter_jejuni_M1_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid159535 
               
               
                 Cas9-31 
                 NC_018521 
                 403056243 
                   
                 Makarova et al 
                 2015 
                 Campylobacter_jejuni_NCTC_ 
               
               
                   
                   
                   
                   
                   
                   
                 11168_BN148_uid174152 
               
               
                 Cas9-32 
                 NC_002163 
                 218563121 
                   
                 Makarova et al 
                 2015 
                 Campylobacter_jejuni_NCTC_ 
               
               
                   
                   
                   
                   
                   
                   
                 11168__ATCC_700819_uid57587 
               
               
                 Cas9-33 
                 NC_018709 
                 407942868 
                   
                 Makarova et al 
                 2015 
                 Campylobacter_jejuni_PT14_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid176499 
               
               
                 Cas9-34 
                 NC_009707 
                 153952471 
                   
                 Makarova et al 
                 2015 
                 Campylobacter_jejuni_doylei_ 
               
               
                   
                   
                   
                   
                   
                   
                 269_97_uid58671 
               
               
                 Cas9-35 
                 NC_014010 
                 294086111 
                   
                 Makarova et al 
                 2015 
                 Candidatus_Puniceispirillum_ 
               
               
                   
                   
                   
                   
                   
                   
                 marinum_IMCC1322_uid47081 
               
               
                 Cas9-36 
                 NC_015846 
                 340622236 
                   
                 Makarova et al 
                 2015 
                 Capnocytophaga_canimorsus_ 
               
               
                   
                   
                   
                   
                   
                   
                 Cc5_uid70727 
               
               
                 Cas9-37 
                 NC_011898 
                 220930482 
                   
                 Makarova et al 
                 2015 
                 Clostridium_cellulolyticum_ 
               
               
                   
                   
                   
                   
                   
                   
                 H10_uid58709 
               
               
                 Cas9-38 
                 NC_021009 
                 479136975 
                   
                 Makarova et al 
                 2015 
                 Coprococcus_catus_ 
               
               
                   
                   
                   
                   
                   
                   
                 GD_7_uid197174 
               
               
                 Cas9-39 
                 NC_015389 
                 328956315 
                   
                 Makarova et al 
                 2015 
                 Coriobacterium_glomerans_ 
               
               
                   
                   
                   
                   
                   
                   
                 PW2_uid65787 
               
               
                 Cas9-40 
                 NC_016782 
                 375289763 
                   
                 Makarova et al 
                 2015 
                 Corynebacterium_diphtheriae_ 
               
               
                   
                   
                   
                   
                   
                   
                 241_uid83607 
               
               
                 Cas9-41 
                 NC_016799 
                 376283539 
                   
                 Makarova et al 
                 2015 
                 Corynebacterium_diphtheriae_ 
               
               
                   
                   
                   
                   
                   
                   
                 31A_uid84309 
               
               
                 Cas9-42 
                 NC_016800 
                 376286566 
                   
                 Makarova et al 
                 2015 
                 Corynebacterium_diphtheriae_ 
               
               
                   
                   
                   
                   
                   
                   
                 BH8_uid84311 
               
               
                 Cas9-43 
                 NC_016801 
                 376289243 
                   
                 Makarova et al 
                 2015 
                 Corynebacterium_diphtheriae_ 
               
               
                   
                   
                   
                   
                   
                   
                 C7__beta__uid84313 
               
               
                 Cas9-44 
                 NC_016786 
                 376244596 
                   
                 Makarova et al 
                 2015 
                 Corynebacterium_diphtheriae_ 
               
               
                   
                   
                   
                   
                   
                   
                 HC01_uid84297 
               
               
                 Cas9-45 
                 NC_016802 
                 376292154 
                   
                 Makarova et al 
                 2015 
                 Corynebacterium_diphtheriae_ 
               
               
                   
                   
                   
                   
                   
                   
                 HC02_uid84317 
               
               
                 Cas9-46 
                 NC_002935 
                 38232678 
                   
                 Makarova et al 
                 2015 
                 Corynebacterium_diphtheriae_ 
               
               
                   
                   
                   
                   
                   
                   
                 NCTC_13129_uid57691 
               
               
                 Cas9-47 
                 NC_016790 
                 376256051 
                   
                 Makarova et al 
                 2015 
                 Corynebacterium_diphtheriae_ 
               
               
                   
                   
                   
                   
                   
                   
                 VA01_uid84305 
               
               
                 Cas9-48 
                 NC_009952 
                 159042956 
                   
                 Makarova et al 
                 2015 
                 Dinoroseobacter_shibae_ 
               
               
                   
                   
                   
                   
                   
                   
                 DFL_12_uid58707 
               
               
                 Cas9-49 
                 NC_015738 
                 339445983 
                   
                 Makarova et al 
                 2015 
                 Eggerthella_YY7918_uid68707 
               
               
                 Cas9-50 
                 NC_010644 
                 187250660 
                   
                 Makarova et al 
                 2015 
                 Elusimicrobium_minutum_ 
               
               
                   
                   
                   
                   
                   
                   
                 Pei191_uid58949 
               
               
                 Cas9-51 
                 NC_021023 
                 479180325 
                   
                 Makarova et al 
                 2015 
                 Enterococcus_7L76_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid197170 
               
               
                 Cas9-52 
                 NC_018221 
                 397699066 
                   
                 Makarova et al 
                 2015 
                 Enterococcus_faecalis_D32_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid171261 
               
               
                 Cas9-53 
                 NC_017316 
                 384512368 
                   
                 Makarova et al 
                 2015 
                 Enterococcus_faecalis_ 
               
               
                   
                   
                   
                   
                   
                   
                 OG1RF_uid54927 
               
               
                 Cas9-54 
                 NC_018081 
                 392988474 
                   
                 Makarova et al 
                 2015 
                 Enterococcus_hirac_ATCC_ 
               
               
                   
                   
                   
                   
                   
                   
                 9790_uid70619 
               
               
                 Cas9-55 
                 NC_022878 
                 558685081 
                   
                 Makarova et al 
                 2015 
                 Enterococcus_mundtii_ 
               
               
                   
                   
                   
                   
                   
                   
                 QU_25_uid229420 
               
               
                 Cas9-56 
                 NC_012781 
                 238924075 
                   
                 Makarova et al 
                 2015 
                 Eubacterium_rectale_ 
               
               
                   
                   
                   
                   
                   
                   
                 ATCC_33656_uid59169 
               
               
                 Cas9-57 
                 NC_017448 
                 385789535 
                   
                 Makarova et al 
                 2015 
                 Fibrobacter_succinogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 S85_uid161919 
               
               
                 Cas9-58 
                 NC_013410 
                 261414553 
                   
                 Makarova et al 
                 2015 
                 Fibrobacter_succinogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 S85_uid41169 
               
               
                 Cas9-59 
                 NC_016630 
                 374307738 
                   
                 Makarova et al 
                 2015 
                 Filifactor_alocis_ATCC_ 
               
               
                   
                   
                   
                   
                   
                   
                 35896_uid46625 
               
               
                 Cas9-60 
                 NC_010376 
                 169823755 
                   
                 Makarova et al 
                 2015 
                 Finegoldia_magna_ATCC_ 
               
               
                   
                   
                   
                   
                   
                   
                 29328_uid58867 
               
               
                 Cas9-61 
                 NC_009613 
                 150025575 
                   
                 Makarova et al 
                 2015 
                 Flavobacterium_psychrophilum_ 
               
               
                   
                   
                   
                   
                   
                   
                 JIP02_86_uid61627 
               
               
                 Cas9-62 
                 NC_015321 
                 327405121 
                   
                 Makarova et al 
                 2015 
                 Fluviicola_taffensis_DSM_ 
               
               
                   
                   
                   
                   
                   
                   
                 16823_uid65271 
               
               
                 Cas9-63 
                 NC_017449 
                 387824704 
                   
                 Makarova et al 
                 2015 
                 Francisella_cf__novicida_ 
               
               
                   
                   
                   
                   
                   
                   
                 3523_uid162107 
               
               
                 Cas9-64 
                 NC_008601 
                 118497352 
                   
                 Makarova et al 
                 2015 
                 Francisella_novicida_ 
               
               
                   
                   
                   
                   
                   
                   
                 U112_uid58499 
               
               
                 Cas9-65 
                 NC_009257 
                 134302318 
                   
                 Makarova et al 
                 2015 
                 Francisella_tularensis_WY96_ 
               
               
                   
                   
                   
                   
                   
                   
                 3418_uid58811 
               
               
                 Cas9-66 
                 NC_007880 
                 89256630 
                   
                 Makarova et al 
                 2015 
                 Francisella_tularensis_holarctica_ 
               
               
                   
                   
                   
                   
                   
                   
                 LVS_uid58595 
               
               
                 Cas9-67 
                 NC_007880 
                 89256631 
                   
                 Makarova et al 
                 2015 
                 Francisella_tularensis_holarctica_ 
               
               
                   
                   
                   
                   
                   
                   
                 LVS_uid58595 
               
               
                 Cas9-68 
                 NC_022196 
                 534508854 
                   
                 Makarova et al 
                 2015 
                 Fusobacterium_3_1_36A2_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid55995 
               
               
                 Cas9-69 
                 NC_022080 
                 530600688 
                   
                 Makarova et al 
                 2015 
                 Geobacillus_JF8_uid215234 
               
               
                 Cas9-70 
                 NC_011365 
                 209542524 
                   
                 Makarova et al 
                 2015 
                 Gluconacetobacter_diazotrophicus_ 
               
               
                   
                   
                   
                   
                   
                   
                 PA1_5_uid59075 
               
               
                 Cas9-71 
                 NC_010125 
                 162147907 
                   
                 Makarova et al 
                 2015 
                 Gluconacetobacter_diazotrophicus_ 
               
               
                   
                   
                   
                   
                   
                   
                 PA1_5_uid61587 
               
               
                 Cas9-72 
                 NC_021021 
                 479173968 
                   
                 Makarova et al 
                 2015 
                 Gordonibacter_pamelaeae_7_ 
               
               
                   
                   
                   
                   
                   
                   
                 10_1_b_uid197167 
               
               
                 Cas9-73 
                 NC_015964 
                 345430422 
                   
                 Makarova et al 
                 2015 
                 Haemophilus_parainflucnzae_ 
               
               
                   
                   
                   
                   
                   
                   
                 T3T1_uid72801 
               
               
                 Cas9-74 
                 NC_020555 
                 471315929 
                   
                 Makarova et al 
                 2015 
                 Helicobacter_cinaedi_ATCC_ 
               
               
                   
                   
                   
                   
                   
                   
                 BAA_847_uid193765 
               
               
                 Cas9-75 
                 NC_017761 
                 386762035 
                   
                 Makarova et al 
                 2015 
                 Helicobacter_cinaedi_ 
               
               
                   
                   
                   
                   
                   
                   
                 PAGU611_uid162219 
               
               
                 Cas9-76 
                 NC_013949 
                 291276265 
                   
                 Makarova et al 
                 2015 
                 Helicobacter_mustelae_ 
               
               
                   
                   
                   
                   
                   
                   
                 12198_uid46647 
               
               
                 Cas9-77 
                 NC_017464 
                 385811609 
                   
                 Makarova et al 
                 2015 
                 Ignavibacterium_album_ 
               
               
                   
                   
                   
                   
                   
                   
                 JCM_16511_uid162097 
               
               
                 Cas9-78 
                 NC_014633 
                 310780384 
                   
                 Makarova et al 
                 2015 
                 Ilyobacter_polytropus_ 
               
               
                   
                   
                   
                   
                   
                   
                 DSM_2926_uid59769 
               
               
                 Cas9-79 
                 NC_015428 
                 331702228 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_buchneri_ 
               
               
                   
                   
                   
                   
                   
                   
                 NRRL_B_30929_uid66205 
               
               
                 Cas9-80 
                 NC_018610 
                 406027703 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_buchneri_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid73657 
               
               
                 Cas9-81 
                 NC_017474 
                 385824065 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_casei_BD_II_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid_162119 
               
               
                 Cas9-82 
                 NC_010999 
                 191639137 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_casei_BL23_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid59237 
               
               
                 Cas9-83 
                 NC_017473 
                 385820880 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_casei_LC2W_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid162121 
               
               
                 Cas9-84 
                 NC_021721 
                 523514789 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_casei_ 
               
               
                   
                   
                   
                   
                   
                   
                 LOCK919_uid210959 
               
               
                 Cas9-85 
                 NC_018641 
                 409997999 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_casei_ 
               
               
                   
                   
                   
                   
                   
                   
                 W56_uid178736 
               
               
                 Cas9-86 
                 NC_014334 
                 301067199 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_casei_Zhang_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid50673 
               
               
                 Cas9-87 
                 NC_017469 
                 385815562 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_delbrueckii_ 
               
               
                   
                   
                   
                   
                   
                   
                 bulgaricus_2038_uid161929 
               
               
                 Cas9-88 
                 NC_017469 
                 385815563 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_delbrueckii_ 
               
               
                   
                   
                   
                   
                   
                   
                 bulgaricus_2038_uid161929 
               
               
                 Cas9-89 
                 NC_017469 
                 385815564 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_delbrueckii_ 
               
               
                   
                   
                   
                   
                   
                   
                 bulgaricus_2038_uid161929 
               
               
                 Cas9-90 
                 NC_017477 
                 385826041 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_johnsonii_ 
               
               
                   
                   
                   
                   
                   
                   
                 DPC_6026_uid162057 
               
               
                 Cas9-91 
                 NC_022112 
                 532357525 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_paracasei_ 
               
               
                   
                   
                   
                   
                   
                   
                 8700_2_uid55295 
               
               
                 Cas9-92 
                 NC_020229 
                 448819853 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_plantarum_ 
               
               
                   
                   
                   
                   
                   
                   
                 ZJ316_uid188689 
               
               
                 Cas9-93 
                 NC_017482 
                 385828839 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_rhamnosus_ 
               
               
                   
                   
                   
                   
                   
                   
                 GG_uid161983 
               
               
                 Cas9-94 
                 NC_013198 
                 258509199 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_rhamnosus_ 
               
               
                   
                   
                   
                   
                   
                   
                 GG_uid59313 
               
               
                 Cas9-95 
                 NC_021723 
                 523517690 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_rhamnosus_ 
               
               
                   
                   
                   
                   
                   
                   
                 LOCK900_uid210957 
               
               
                 Cas9-96 
                 NC_017481 
                 385839898 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_salivarius_ 
               
               
                   
                   
                   
                   
                   
                   
                 CECT_5713_uid162005 
               
               
                 Cas9-97 
                 NC_017481 
                 385839899 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_salivarius_ 
               
               
                   
                   
                   
                   
                   
                   
                 CECT_5713_uid162005 
               
               
                 Cas9-98 
                 NC_017481 
                 385839900 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_salivarius_ 
               
               
                   
                   
                   
                   
                   
                   
                 CECT_5713_uid162005 
               
               
                 Cas9-99 
                 NC_007929 
                 90961083 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_salivarius_ 
               
               
                   
                   
                   
                   
                   
                   
                 UCC118_uid58233 
               
               
                 Cas9-100 
                 NC_007929 
                 90961084 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_salivarius_ 
               
               
                   
                   
                   
                   
                   
                   
                 UCC118_uid58233 
               
               
                 Cas9-101 
                 NC_015978 
                 347534532 
                   
                 Makarova et al 
                 2015 
                 Lactobacillus_sanfranciscensis_ 
               
               
                   
                   
                   
                   
                   
                   
                 TMW_1_1304_uid72937 
               
               
                 Cas9-102 
                 NC_006368 
                 54296138 
                   
                 Makarova et al 
                 2015 
                 Legionella_pneumophila_ 
               
               
                   
                   
                   
                   
                   
                   
                 Paris_uid58211 
               
               
                 Cas9-103 
                 NC_018631 
                 406600271 
                   
                 Makarova et al 
                 2015 
                 Leuconostoc_gelidum_JB7_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid175682 
               
               
                 Cas9-104 
                 NC_003212 
                 16801805 
                   
                 Makarova et al 
                 2015 
                 Listeria_innocua_Clip11262_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid61567 
               
               
                 Cas9-105 
                 NC_017544 
                 386044902 
                   
                 Makarova et al 
                 2015 
                 Listeria_monocytogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 10403S_uid54461 
               
               
                 Cas9-106 
                 NC_022568 
                 550898770 
                   
                 Makarova et al 
                 2015 
                 Listeria_monocytogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 EGD_uid223288 
               
               
                 Cas9-107 
                 NC_017545 
                 386048324 
                   
                 Makarova et al 
                 2015 
                 Listeria_monocytogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 J0161_uid54459 
               
               
                 Cas9-108 
                 NC_018586 
                 405756714 
                   
                 Makarova et al 
                 2015 
                 Listeria_monocytogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 SLCC2540_uid175106 
               
               
                 Cas9-109 
                 NC_018592 
                 404411844 
                   
                 Makarova et al 
                 2015 
                 Listeria_monocytogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 SLCC5850_uid175110 
               
               
                 Cas9-110 
                 NC_018587 
                 404282159 
                   
                 Makarova et al 
                 2015 
                 Listeria_monocytogenes_serotype_ 
               
               
                   
                   
                   
                   
                   
                   
                 1_2b_SLCC2755_uid52455 
               
               
                 Cas9-111 
                 NC_018591 
                 404287973 
                   
                 Makarova et al 
                 2015 
                 Listeria_monocytogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 serotype_7_SLCC2482_uid174871 
               
               
                 Cas9-112 
                 NC_019949 
                 433625054 
                   
                 Makarova et al 
                 2015 
                 Mycoplasma_cynos_C142_uid184824 
               
               
                 Cas9-113 
                 NC_018412 
                 401771107 
                   
                 Makarova et al 
                 2015 
                 Mycoplasma_gallisepticum_ 
               
               
                   
                   
                   
                   
                   
                   
                 CA06_2006_052_5_2P_uid172630 
               
               
                 Cas9-114 
                 NC_017503 
                 385326554 
                   
                 Makarova et al 
                 2015 
                 Mycoplasma_gallisepticum_ 
               
               
                   
                   
                   
                   
                   
                   
                 F_uid162001 
               
               
                 Cas9-115 
                 NC_018407 
                 401767318 
                   
                 Makarova et al 
                 2015 
                 Mycoplasma_gallisepticum_ 
               
               
                   
                   
                   
                   
                   
                   
                 NC95_13295_2_2P_uid172625 
               
               
                 Cas9-116 
                 NC_018408 
                 401768090 
                   
                 Makarova et al 
                 2015 
                 Mycoplasma_gallisepticum_ 
               
               
                   
                   
                   
                   
                   
                   
                 NC96_1596_4_2P_uid172626 
               
               
                 Cas9-117 
                 NC_018409 
                 401768851 
                   
                 Makarova et al 
                 2015 
                 Mycoplasma_gallisepticum_ 
               
               
                   
                   
                   
                   
                   
                   
                 NY01_2001_047_5_1P_uid172627 
               
               
                 Cas9-118 
                 NC_017502 
                 385325798 
                   
                 Makarova et al 
                 2015 
                 Mycoplasma_gallisepticum_ 
               
               
                   
                   
                   
                   
                   
                   
                 R_high_uid161999 
               
               
                 Cas9-119 
                 NC_004829 
                 294660600 
                   
                 Makarova et al 
                 2015 
                 Mycoplasma_gallisepticum_ 
               
               
                   
                   
                   
                   
                   
                   
                 R_low__uid57993 
               
               
                 Cas9-120 
                 NC_023030 
                 565627373 
                   
                 Makarova et al 
                 2015 
                 Mycoplasma_gallisepticum_ 
               
               
                   
                   
                   
                   
                   
                   
                 S6_uid200523 
               
               
                 Cas9-121 
                 NC_018410 
                 401769598 
                   
                 Makarova et al 
                 2015 
                 Mycoplasma_gallisepticum_ 
               
               
                   
                   
                   
                   
                   
                   
                 WI01_2001_043_13_2P_uid172628 
               
               
                 Cas9-122 
                 NC_006908 
                 47458868 
                   
                 Makarova et al 
                 2015 
                 Mycoplasma_mobile_163K_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid58077 
               
               
                 Cas9-123 
                 NC_007294 
                 71894592 
                   
                 Makarova et al 
                 2015 
                 Mycoplasma_synoviae_53_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid58061 
               
               
                 Cas9-124 
                 NC_014752 
                 313669044 
                   
                 Makarova et al 
                 2015 
                 Neisseria_lactamica_020_06_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid60851 
               
               
                 Cas9-125 
                 NC_010120 
                 161869390 
                   
                 Makarova et al 
                 2015 
                 Neisseria_meningitidis_053442_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid58587 
               
               
                 Cas9-126 
                 NC_017501 
                 385324780 
                   
                 Makarova et al 
                 2015 
                 Neisseria_meningitidis_8013_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid161967 
               
               
                 Cas9-127 
                 NC_017512 
                 385337435 
                   
                 Makarova et al 
                 2015 
                 Neisseria_meningitidis_WUE_ 
               
               
                   
                   
                   
                   
                   
                   
                 2594_uid162093 
               
               
                 Cas9-128 
                 NC_003116 
                 218767588 
                   
                 Makarova et al 
                 2015 
                 Neisseria_meningitidis_ 
               
               
                   
                   
                   
                   
                   
                   
                 Z2491_uid57819 
               
               
                 Cas9-129 
                 NC_013016 
                 254804356 
                   
                 Makarova et al 
                 2015 
                 Neisseria_meningitidis_ 
               
               
                   
                   
                   
                   
                   
                   
                 alpha_14_uid61649 
               
               
                 Cas9-130 
                 NC_014935 
                 319957206 
                   
                 Makarova et al 
                 2015 
                 Nitratifractor_salsuginis_ 
               
               
                   
                   
                   
                   
                   
                   
                 DSM_16511_uid62183 
               
               
                 Cas9-131 
                 NC_015222 
                 325983496 
                   
                 Makarova et al 
                 2015 
                 Nitrosomonas_AL212_uid55727 
               
               
                 Cas9-132 
                 NC_014363 
                 302336020 
                   
                 Makarova et al 
                 2015 
                 Olsenella_uli_DSM_ 
               
               
                   
                   
                   
                   
                   
                   
                 7084_uid51367 
               
               
                 Cas9-133 
                 NC_018016 
                 392391493 
                   
                 Makarova et al 
                 2015 
                 Omithobacterium_rhinotracheale_ 
               
               
                   
                   
                   
                   
                   
                   
                 DSM_15997_uid168256 
               
               
                 Cas9-134 
                 NC_009719 
                 154250555 
                   
                 Makarova et al 
                 2015 
                 Parvibaculum_lavamentivorans_ 
               
               
                   
                   
                   
                   
                   
                   
                 DS_1_uid58739 
               
               
                 Cas9-135 
                 NC_002663 
                 15602992 
                   
                 Makarova et al 
                 2015 
                 Pasteurella_multocida_ 
               
               
                   
                   
                   
                   
                   
                   
                 Pm70_uid57627 
               
               
                 Cas9-136 
                 NC_022780 
                 557607382 
                   
                 Makarova et al 
                 2015 
                 Pediococcus_pentosaceus_ 
               
               
                   
                   
                   
                   
                   
                   
                 SL4_uid227215 
               
               
                 Cas9-137 
                 NC_017861 
                 387132277 
                   
                 Makarova et al 
                 2015 
                 Prevotella_intermedia_17_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid163151 
               
               
                 Cas9-138 
                 NC_014033 
                 294674019 
                   
                 Makarova et al 
                 2015 
                 Prevotella_ruminicola_23_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid47507 
               
               
                 Cas9-139 
                 NC_018721 
                 408489713 
                   
                 Makarova et al 
                 2015 
                 Psychroflexus_torquis_ATCC_ 
               
               
                   
                   
                   
                   
                   
                   
                 700755_uid54205 
               
               
                 Cas9-140 
                 NC_007925 
                 90425961 
                   
                 Makarova et al 
                 2015 
                 Rhodopseudomonas_palustris_ 
               
               
                   
                   
                   
                   
                   
                   
                 BisB18_uid58443 
               
               
                 Cas9-141 
                 NC_007958 
                 91975509 
                   
                 Makarova et al 
                 2015 
                 Rhodopseudomonas_palustris_ 
               
               
                   
                   
                   
                   
                   
                   
                 BisB5_uid58441 
               
               
                 Cas9-142 
                 NC_007643 
                 83591793 
                   
                 Makarova et al 
                 2015 
                 Rhodospirilluni_rubrum_ATCC_ 
               
               
                   
                   
                   
                   
                   
                   
                 11170_uid57655 
               
               
                 Cas9-143 
                 NC_017584 
                 386348484 
                   
                 Makarova et al 
                 2015 
                 Rhodospirilluni_rubrum_ 
               
               
                   
                   
                   
                   
                   
                   
                 F11_uid162149 
               
               
                 Cas9-144 
                 NC_017045 
                 383485594 
                   
                 Makarova et al 
                 2015 
                 Riemerella_anatipestifer_ATCC_ 
               
               
                   
                   
                   
                   
                   
                   
                 11845__DSM_15868_uid159857 
               
               
                 Cas9-145 
                 NC_018609 
                 407451859 
                   
                 Makarova et al 
                 2015 
                 Riemerella_anatipestifer_RA_ 
               
               
                   
                   
                   
                   
                   
                   
                 CH_1_uid175469 
               
               
                 Cas9-146 
                 NC_020125 
                 442314523 
                   
                 Makarova et al 
                 2015 
                 Riemerella_anatipestifer_RA_ 
               
               
                   
                   
                   
                   
                   
                   
                 CH_2_uid186548 
               
               
                 Cas9-147 
                 NC_017569 
                 386321727 
                   
                 Makarova et al 
                 2015 
                 Riemerella_anatipestifer_RA_ 
               
               
                   
                   
                   
                   
                   
                   
                 GD_uid162013 
               
               
                 Cas9-148 
                 NC_021040 
                 479204792 
                   
                 Makarova et al 
                 2015 
                 Roseburia_intestinalis_uid197164 
               
               
                 Cas9-149 
                 NC_020561 
                 470213512 
                   
                 Makarova et al 
                 2015 
                 Sphingomonas_MM_1_uid193771 
               
               
                 Cas9-150 
                 NC_015152 
                 325972003 
                   
                 Makarova et al 
                 2015 
                 Spirochaeta_Buddy_uid63633 
               
               
                 Cas9-151 
                 NC_022998 
                 563693590 
                   
                 Makarova et al 
                 2015 
                 Spiroplasma_apis_B31_uid230613 
               
               
                 Cas9-152 
                 NC_021284 
                 507384108 
                   
                 Makarova et al 
                 2015 
                 Spiroplasma_syrphidicola_ 
               
               
                   
                   
                   
                   
                   
                   
                 EA_1_uid205054 
               
               
                 Cas9-153 
                 NC_022737 
                 556591142 
                   
                 Makarova et al 
                 2015 
                 Staphylococcus_pasteuri_ 
               
               
                   
                   
                   
                   
                   
                   
                 SP1_uid226267 
               
               
                 Cas9-154 
                 NC_017568 
                 386318630 
                   
                 Makarova et al 
                 2015 
                 Staphylococcus_pseudintermedius_ 
               
               
                   
                   
                   
                   
                   
                   
                 ED99_uid162109 
               
               
                 Cas9-155 
                 NC_013515 
                 269123826 
                   
                 Makarova et al 
                 2015 
                 Streptobacillus_moniliformis_ 
               
               
                   
                   
                   
                   
                   
                   
                 DSM_12112_uid41863 
               
               
                 Cas9-156 
                 NC_022584 
                 552737657 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_I_G2_uid224251 
               
               
                 Cas9-157 
                 NC_021485 
                 512539130 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_agalactiae_ 
               
               
                   
                   
                   
                   
                   
                   
                 09mas018883_uid208674 
               
               
                 Cas9-158 
                 NC_004116 
                 22537057 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_agalactiae_ 
               
               
                   
                   
                   
                   
                   
                   
                 2603V_R_uid57943 
               
               
                 Cas9-159 
                 NC_021195 
                 494703075 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_agalactiae_2_ 
               
               
                   
                   
                   
                   
                   
                   
                 22_uid202215 
               
               
                 Cas9-160 
                 NC_007432 
                 76788458 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_agalactiae_ 
               
               
                   
                   
                   
                   
                   
                   
                 A909_uid57935 
               
               
                 Cas9-161 
                 NC_018646 
                 406709383 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_agalactiae_ 
               
               
                   
                   
                   
                   
                   
                   
                 GD201008_001_uid175780 
               
               
                 Cas9-162 
                 NC_021486 
                 512544670 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_agalactiae_ 
               
               
                   
                   
                   
                   
                   
                   
                 ILRI005_uid208676 
               
               
                 Cas9-163 
                 NC_021507 
                 512698372 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_agalactiae_ 
               
               
                   
                   
                   
                   
                   
                   
                 ILRI112_uid208675 
               
               
                 Cas9-164 
                 NC_004368 
                 25010965 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_agalactiae_ 
               
               
                   
                   
                   
                   
                   
                   
                 NEM316_uid61585 
               
               
                 Cas9-165 
                 NC_019048 
                 410594450 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_agalactiae_ 
               
               
                   
                   
                   
                   
                   
                   
                 SA20_06_uid178722 
               
               
                 Cas9-166 
                 NC_022244 
                 538370328 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_anginosus_ 
               
               
                   
                   
                   
                   
                   
                   
                 C1051_uid218003 
               
               
                 Cas9-167 
                 NC_019042 
                 410494913 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_dysgalactiae_ 
               
               
                   
                   
                   
                   
                   
                   
                 equisimilis_AC_2713_uid178644 
               
               
                 Cas9-168 
                 NC_017567 
                 386317166 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_dysgalactiae_ 
               
               
                   
                   
                   
                   
                   
                   
                 equisimilis_ATCC_12394_uid161979 
               
               
                 Cas9-169 
                 NC_012891 
                 251782637 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_dysgalactiae_ 
               
               
                   
                   
                   
                   
                   
                   
                 equisimilis_GGS_124_uid59103 
               
               
                 Cas9-170 
                 NC_018712 
                 408401787 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_dysgalactiae_ 
               
               
                   
                   
                   
                   
                   
                   
                 equisimilis_RE378_uid176684 
               
               
                 Cas9-171 
                 NC_011134 
                 195978435 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_equi_zooepidemicus_ 
               
               
                   
                   
                   
                   
                   
                   
                 MGCS10565_uid59263 
               
               
                 Cas9-172 
                 NC_017576 
                 386338081 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_gallolyticus_ 
               
               
                   
                   
                   
                   
                   
                   
                 ATCC_43143_uid162103 
               
               
                 Cas9-173 
                 NC_017576 
                 386338091 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_gallolyticus_ 
               
               
                   
                   
                   
                   
                   
                   
                 ATCC_43143_uid162103 
               
               
                 Cas9-174 
                 NC_015215 
                 325978669 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_gallolyticus_ 
               
               
                   
                   
                   
                   
                   
                   
                 ATCC_BAA_2069_uid63617 
               
               
                 Cas9-175 
                 NC_013798 
                 288905632 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_gallolyticus_ 
               
               
                   
                   
                   
                   
                   
                   
                 UCN34_uid46061 
               
               
                 Cas9-176 
                 NC_013798 
                 288905639 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_gallolyticus_ 
               
               
                   
                   
                   
                   
                   
                   
                 UCN34_uid46061 
               
               
                 Cas9-177 
                 NC_009785 
                 157150687 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_gordonii_ 
               
               
                   
                   
                   
                   
                   
                   
                 Challis_substr_CH1_uid57667 
               
               
                 Cas9-178 
                 NC_016826 
                 379705580 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_infantarius_ 
               
               
                   
                   
                   
                   
                   
                   
                 CJ18_uid87033 
               
               
                 Cas9-179 
                 NC_021314 
                 508127396 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_iniae_ 
               
               
                   
                   
                   
                   
                   
                   
                 SF1_uid206041 
               
               
                 Cas9-180 
                 NC_021314 
                 508127399 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_iniae_ 
               
               
                   
                   
                   
                   
                   
                   
                 SF1_uid206041 
               
               
                 Cas9-181 
                 NC_022246 
                 538379999 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_intermedius_ 
               
               
                   
                   
                   
                   
                   
                   
                 B196_uid218000 
               
               
                 Cas9-182 
                 NC_021900 
                 527330434 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_lutetiensis_ 
               
               
                   
                   
                   
                   
                   
                   
                 033_uid213397 
               
               
                 Cas9-183 
                 NC_016749 
                 374338350 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_macedonicus_ 
               
               
                   
                   
                   
                   
                   
                   
                 ACA_DC_198_uid81631 
               
               
                 Cas9-184 
                 NC_018089 
                 397650022 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_mutans_ 
               
               
                   
                   
                   
                   
                   
                   
                 GS_5_uid169223 
               
               
                 Cas9-185 
                 NC_017768 
                 387785882 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_mutans_ 
               
               
                   
                   
                   
                   
                   
                   
                 LJ23_uid162197 
               
               
                 Cas9-186 
                 NC_013928 
                 290580220 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_mutans_ 
               
               
                   
                   
                   
                   
                   
                   
                 NN2025_uid46353 
               
               
                 Cas9-187 
                 NC_004350 
                 24379809 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_mutans_ 
               
               
                   
                   
                   
                   
                   
                   
                 UA159_uid57947 
               
               
                 Cas9-188 
                 NC_015600 
                 336064611 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_pasteurianus_ 
               
               
                   
                   
                   
                   
                   
                   
                 ATCC_43144_uid68019 
               
               
                 Cas9-189 
                 NC_018936 
                 410680443 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_pyogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 A20_uid178106 
               
               
                 Cas9-190 
                 NC_020540 
                 470200927 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_pyogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 M1_476_uid193766 
               
               
                 Cas9-191 
                 NC_002737 
                 15675041 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_pyogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 M1_GAS_uid57845 
               
               
                 Cas9-192 
                 NC_008022 
                 94990395 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_pyogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 MGAS10270_uid58571 
               
               
                 Cas9-193 
                 NC_008024 
                 94994317 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_pyogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 MGAS10750_uid58575 
               
               
                 Cas9-194 
                 NC_017040 
                 383479946 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_pyogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 MGAS15252_uid158037 
               
               
                 Cas9-195 
                 NC_017053 
                 383493861 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_pyogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 MGAS1882_uid158061 
               
               
                 Cas9-196 
                 NC_008023 
                 94992340 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_pyogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 MGAS2096_uid58573 
               
               
                 Cas9-197 
                 NC_004070 
                 21910213 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_pyogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 MGAS315_uid57911 
               
               
                 Cas9-198 
                 NC_007297 
                 71910582 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_pyogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 MGAS5005_uid58337 
               
               
                 Cas9-199 
                 NC_007296 
                 71903413 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_pyogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 MGAS6180_uid58335 
               
               
                 Cas9-200 
                 NC_008021 
                 94988516 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_pyogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 MGAS9429_uid58569 
               
               
                 Cas9-201 
                 NC_011375 
                 209559356 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_pyogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 NZ131_uid59035 
               
               
                 Cas9-202 
                 NC_004606 
                 28896088 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_pyogenes_ 
               
               
                   
                   
                   
                   
                   
                   
                 SSI_1_uid57895 
               
               
                 Cas9-203 
                 NC_017595 
                 387783792 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_salivarius_ 
               
               
                   
                   
                   
                   
                   
                   
                 JIM8777_uid162145 
               
               
                 Cas9-204 
                 NC_017620 
                 386584496 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_suis_D9_uid162125 
               
               
                 Cas9-205 
                 NC_017950 
                 389856936 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_suis_ST1_uid167482 
               
               
                 Cas9-206 
                 NC_015433 
                 330833104 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_suis_ST3_uid66327 
               
               
                 Cas9-207 
                 NC_006449 
                 55822627 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_thermophilus_ 
               
               
                   
                   
                   
                   
                   
                   
                 CNRZ1066_uid58221 
               
               
                 Cas9-208 
                 NC_017581 
                 386344353 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_thermophilus_ 
               
               
                   
                   
                   
                   
                   
                   
                 JIM_8232_uid162157 
               
               
                 Cas9-209 
                 NC_008532 
                 116627542 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_thermophilus_ 
               
               
                   
                   
                   
                   
                   
                   
                 LMD_9_uid58327 
               
               
                 Cas9-210 
                 NC_008532 
                 116628213 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_thermophilus_ 
               
               
                   
                   
                   
                   
                   
                   
                 LMD_9_uid58327 
               
               
                 Cas9-211 
                 NC_006448 
                 55820735 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_thermophilus_ 
               
               
                   
                   
                   
                   
                   
                   
                 LMG_1831_uid58219 
               
               
                 Cas9-212 
                 NC_017927 
                 387909441 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_thermophilus_ 
               
               
                   
                   
                   
                   
                   
                   
                 MN_ZLW_002_uid166827 
               
               
                 Cas9-213 
                 NC_017927 
                 387910220 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_thermophilus_ 
               
               
                   
                   
                   
                   
                   
                   
                 MN_ZLW_002_uid166827 
               
               
                 Cas9-214 
                 NC_017563 
                 386086348 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_thermophilus_ 
               
               
                   
                   
                   
                   
                   
                   
                 ND03_uid162015 
               
               
                 Cas9-215 
                 NC_017563 
                 386087120 
                   
                 Makarova et al 
                 2015 
                 Streptococcus_thermophilus_ 
               
               
                   
                   
                   
                   
                   
                   
                 ND03_uid162015 
               
               
                 Cas9-216 
                 NC_017958 
                 389874754 
                   
                 Makarova et al 
                 2015 
                 Tistrella_mobilis_KA081020_ 
               
               
                   
                   
                   
                   
                   
                   
                 065_uid167486 
               
               
                 Cas9-217 
                 NC_002967 
                 42525843 
                   
                 Makarova et al 
                 2015 
                 Treponema_denticola_ATCC_ 
               
               
                   
                   
                   
                   
                   
                   
                 35405_uid57583 
               
               
                 Cas9-218 
                 NC_022097 
                 530892607 
                   
                 Makarova et al 
                 2015 
                 Treponema_pedis_T_A4_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid215715 
               
               
                 Cas9-219 
                 NC_008786 
                 121608211 
                   
                 Makarova et al 
                 2015 
                 Verminephrobacter_eiseniae_ 
               
               
                   
                   
                   
                   
                   
                   
                 EF01_2_uid58675 
               
               
                 Cas9-220 
                 NC_021826 
                 525888882 
                   
                 Makarova et al 
                 2015 
                 Vibrio_parahaemolyticus_O1_ 
               
               
                   
                   
                   
                   
                   
                   
                 K33_CDC_K4557_uid212977 
               
               
                 Cas9-221 
                 NC_021834 
                 525913263 
                   
                 Makarova et al 
                 2015 
                 Vibrio_parahaemolyticus_O1_ 
               
               
                   
                   
                   
                   
                   
                   
                 K33_CDC_K4557_uid212977 
               
               
                 Cas9-222 
                 NC_021837 
                 525919586 
                   
                 Makarova et al 
                 2015 
                 Vibrio_parahaemolyticus_O1_ 
               
               
                   
                   
                   
                   
                   
                   
                 K33_CDC_K4557_uid212977 
               
               
                 Cas9-223 
                 NC_021838 
                 525927253 
                   
                 Makarova et al 
                 2015 
                 Vibrio_parahaemolyticus_O1_ 
               
               
                   
                   
                   
                   
                   
                   
                 K33_CDC_K4557_uid212977 
               
               
                 Cas9-224 
                 NC_015144 
                 325955459 
                   
                 Makarova et al 
                 2015 
                 Weeksella_virosa_DSM_16922_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid63627 
               
               
                 Cas9-225 
                 NC_005090 
                 34557790 
                   
                 Makarova et al 
                 2015 
                 Wolinella_succinogenes_DSM_ 
               
               
                   
                   
                   
                   
                   
                   
                 1740_uid61591 
               
               
                 Cas9-226 
                 NC_005090 
                 34557932 
                   
                 Makarova et al 
                 2015 
                 Wolinella_succinogenes_DSM_ 
               
               
                   
                   
                   
                   
                   
                   
                 1740_uid61591 
               
               
                 Cas9-227 
                 NC_014041 
                 295136244 
                   
                 Makarova et al 
                 2015 
                 Zunongwangia_profunda_ 
               
               
                   
                   
                   
                   
                   
                   
                 SM_A87_uid48073 
               
               
                 Cas9-228 
                 NC_014366 
                 304313029 
                   
                 Makarova et al 
                 2015 
                 gamma_proteobacterium_Hd_ 
               
               
                   
                   
                   
                   
                   
                   
                 N1_uid51635 
               
               
                 Cas9-229 
                 NC_020419 
                 189485058 
                   
                 Makarova et al 
                 2015 
                 uncultured_Termite_group_1_ 
               
               
                   
                   
                   
                   
                   
                   
                 bacterium_phylotype_Rs_D17_uid59059 
               
               
                 Cas9-230 
                 NC_020419 
                 189485059 
                   
                 Makarova et al 
                 2015 
                 uncultured_Termite_group_1_ 
               
               
                   
                   
                   
                   
                   
                   
                 bacterium_phylotype_Rs_D17_uid59059 
               
               
                 Cas9-231 
                 NC_020419 
                 189485225 
                   
                 Makarova et al 
                 2015 
                 uncultured_Termite_group_1_ 
               
               
                   
                   
                   
                   
                   
                   
                 bacterium_phylotype_Rs_D17_uid59059 
               
               
                 Cas9-232 
                 NC_016001 
                 347536497 
                   
                 Makarova et al 
                 2015 
                 Flavobacterium_branchiophilum_ 
               
               
                   
                   
                   
                   
                   
                   
                 FL_15_uid73421 
               
               
                 Cas9-233 
                 NC_016510 
                 365959402 
                   
                 Makarova et al 
                 2015 
                 Flavobacterium_columnare_ 
               
               
                   
                   
                   
                   
                   
                   
                 ATCC_49512_uid80731 
               
               
                 Cpf1-1 
                 NC_012778 
                 238917342 
                   
                 Makarova et al 
                 2015 
                 Eubacterium_eligens_ATCC_ 
               
               
                   
                   
                   
                   
                   
                   
                 27750_uid59171 
               
               
                 Cpf1-2 
                 NC_017450 
                 385793363 
                   
                 Makarova et al 
                 2015 
                 Francisella_cf_novicida_Fx_ 
               
               
                   
                   
                   
                   
                   
                   
                 1_uid162105 
               
               
                 Cpf1-3 
                 NC_008601 
                 118497971 
                   
                 Makarova et al 
                 2015 
                 Francisella_novicida_U112_ 
               
               
                   
                   
                   
                   
                   
                   
                 uid58499 
               
               
                 Cpf1-4 
                 NC_010336 
                 167627877 
                   
                 Makarova et al 
                 2015 
                 Francisella_philomiragia_ATCC_ 
               
               
                   
                   
                   
                   
                   
                   
                 25017_uid59105 
               
               
                 Cpf1-5 
                 NC_010336 
                 167627878 
                   
                 Makarova et al 
                 2015 
                 Francisella_philomiragia_ATCC_ 
               
               
                   
                   
                   
                   
                   
                   
                 25017_uid59105 
               
               
                 Cpf1-6 
                 NC_020913 
                 478482906 
                   
                 Makarova et al 
                 2015 
                 archaeon_Mx1201_uid196597 
               
               
                   
               
            
           
         
       
     
     The article “a” and “an” are used herein to refer to one or more than one (i.e., to at least one) of the grammatical object of the article. By way of example, “an element” means one or more element. 
     All publications and patent applications mentioned in the specification are indicative of the level of those skilled in the art to which this invention pertains. All publications and patent applications are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. 
     Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be obvious that certain changes and modifications may be practiced within the scope of the appended claims. 
     Non-limiting embodiments include: 
     1. A method for identifying a variant of a clustered regularly-interspaced short palindromic repeat (CRISPR) RNA-guided nuclease (RGN) gene of interest comprising: 
     a) preparing DNA for hybridization from a complex sample comprising a variant of a CRISPR RGN gene of interest, thereby forming a prepared sample DNA comprising said variant of said CRISPR RGN gene of interest; 
     b) mixing said prepared sample DNA with a labeled bait pool comprising polynucleotide sequences complementary to said CRISPR RGN gene of interest; 
     c) hybridizing said prepared sample DNA to said labeled bait pool under conditions that allow for hybridization of a labeled bait in said labeled bait pool with said variant of said CRISPR RGN gene of interest to form one or more hybridization complexes comprising captured DNA; 
     d) sequencing said captured DNA; and 
     e) analyzing said sequenced captured DNA to identify said variant of said CRISPR RGN gene of interest. 
     2. The method of embodiment 1, wherein said complex sample is an environmental sample. 
     3. The method of embodiment 1, wherein said complex sample is a mixed culture of at least two organisms. 
     4. The method of embodiment 1, wherein said complex sample is a mixed culture of more than two organisms collected from a culture. 
     5. The method of any one of embodiments 1-4, wherein said labeled baits are specific for at least 10 CRISPR RGN genes of interest. 
     6. The method of embodiment 5, wherein said labeled baits are specific for at least 300 CRISPR RGN genes of interest. 
     7. The method of any one of embodiments 1-6, wherein said labeled bait pool comprises at least 1,000, at least 5,000, at least 10,000, at least 20,000, at least 30,000, at least 40,000, or at least 50,000 labeled baits. 
     8. The method of any of embodiments 1-7, wherein at least 50 distinct labeled baits are mixed with said prepared sample DNA. 
     9. The method of any one of embodiments 1-8, wherein said labeled baits are 50-200 nt, 70-150 nt, 100-140 nt, or 110-130 nt in length. 
     10. The method of any one of embodiments 1-9, wherein said labeled baits comprise overlapping labeled baits, said overlapping labeled baits comprising at least two labeled baits that are complementary to a portion of a CRISPR RGN gene of interest, wherein the at least two labeled baits comprise different DNA sequences that are overlapping. 
     11. The method of embodiment 10, wherein at least 10, at least 30, at least 60, at least 90, or at least 120 nucleotides of each overlapping labeled bait overlap with at least one other overlapping labeled bait. 
     12. The method of any one of embodiments 1-11, wherein said prepared sample DNA is enriched prior to mixing with said labeled baits. 
     13. The method of any one of embodiments 1-12, wherein said one or more hybridization complex is captured and purified from unbound prepared sample DNA. 
     14. The method of embodiment 13, wherein said one or more hybridization complex is captured using a binding partner of said label of said labeled baits attached to a solid phase. 
     15. The method of embodiment 14, wherein said solid phase is a magnetic bead. 
     16. The method of any one of embodiments 1-11, wherein steps a), b), and c) are performed using an enrichment kit for multiplex sequencing. 
     17. The method of any one of embodiments 1-11, wherein captured DNA from said one or more hybridization complex is amplified and index tagged prior to said sequencing. 
     18. The method of any one of embodiments 1-17, wherein said sequencing comprises multiplex sequencing with gene fragments from different environmental samples. 
     19. The method of any one of embodiments 1-18, wherein said labeled baits cover each CRISPR RGN gene of interest by at least 2×. 
     20. The method of any one of embodiments 1-19, wherein said analyzing said sequenced captured DNA comprises performing a sequence similarity search using the sequenced captured DNA against a database of known CRISPR RGN sequences or domains. 
     21. The method of any one of embodiments 1-19, wherein said analyzing said sequenced captured DNA comprises identifying a full length CRISPR RGN gene sequence of said variant by assembling sequences of said captured DNA and identifying said variant from said full length gene sequence by performing a sequence similarity search using the full length gene sequence against a database of known CRISPR RGN sequences or domains. 
     22. The method of any one of embodiments 1-21, wherein said variant of said CRISPR RGN gene of interest has less than 95% identity to said CRISPR RGN gene of interest. 
     23. The method of any one of embodiments 1-22, wherein said labeled bait pool further comprises polynucleotide sequences complementary to sequences flanking said CRISPR RGN gene of interest, and wherein said method further comprises analyzing said sequenced captured DNA for sequences flanking said variant CRISPR RGN gene to identify a sequence encoding a tracrRNA of said variant of said CRISPR RGN gene of interest. 
     24. The method of embodiment 23, wherein said flanking sequences comprise about 180 nucleotides on either side of said CRISPR RGN gene of interest. 
     25. The method of embodiment 23 or 24, wherein said labeled baits cover each CRISPR RGN gene of interest and said flanking sequences by at least 2×. 
     26. The method of any one of embodiments 23-25, wherein analyzing said flanking sequences comprises performing a sequence similarity search using the flanking sequences against a database of known CRISPR tracrRNA sequences. 
     27. The method of any one of embodiments 23-26, wherein said method further comprises assaying a guide RNA comprising said tracrRNA for binding between the guide RNA and said variant of said CRISPR RGN gene of interest. 
     28. The method of any one of embodiments 1-22, wherein said method further comprises assaying a guide RNA comprising a crRNA for binding between the guide RNA and said variant of said CRISPR RGN gene of interest. 
     29. The method of embodiment 27 or 28, wherein said method further comprises identifying a protospacer adjacent motif (PAM) and assaying said variant of said CRISPR RGN gene of interest and said guide RNA for binding to a target nucleotide sequence of interest adjacent to said PAM. 
     30. The method of embodiment 29, wherein said method further comprises assaying said variant of said CRISPR RGN gene of interest and said guide RNA for cleaving a target nucleotide sequence of interest. 
     31. A method for preparing an RNA bait pool for the identification of variants of a CRISPR RGN gene of interest comprising: 
     a) identifying overlapping fragments of a DNA sequence of at least one CRISPR RGN gene of interest, wherein said overlapping fragments span the entire DNA sequence of said CRISPR RGN gene of interest; 
     b) synthesizing RNA baits complementary to said DNA sequence fragments; 
     c) labeling said RNA baits with a detectable label; and 
     d) combining said labeled RNA baits to form said RNA bait pool. 
     32. The method of embodiment 31, wherein said RNA baits are 50-200 nt, 70-150 nt, 100-140 nt, or 110-130 nt in length. 
     33. The method of embodiment 31 or 32, wherein said RNA bait pool is specific for at least 10 CRISPR RGN genes of interest. 
     34. The method of any one of embodiments 31-33, wherein said RNA bait pool comprises at least 1,000, at least 5,000, at least 10,000, at least 20,000, at least 30,000, at least 40,000, or at least 50,000 RNA baits. 
     35. The method of any one of embodiments 31-34, wherein step a) further comprises obtaining flanking DNA sequences of said at least one CRISPR RGN gene of interest, and wherein said overlapping fragments span the entire DNA sequence of said CRISPR RGN gene of interest and said flanking sequences. 
     36. The method of embodiment 35, wherein said flanking sequences comprise about 180 nucleotides on either side of said CRISPR RGN gene of interest. 
     37. A composition comprising the RNA bait pool produced by the method of any one of embodiments 31-36. 
     38. A composition comprising an RNA bait pool, wherein said RNA bait pool comprises overlapping RNA baits specific for at least one CRISPR RGN gene of interest. 
     39. The composition of embodiment 38, wherein said RNA baits are 50-200 nt, 70-150 nt, 100-140 nt, or 110-130 nt in length. 
     40. The composition of embodiment 38 or 39, wherein said RNA bait pool is specific for at least 10 CRISPR RGN genes of interest. 
     41. The composition of any one of embodiments 38-40, wherein said RNA bait pool comprises at least 1,000, at least 5,000, at least 10,000, at least 20,000, at least 30,000, at least 40,000, or at least 50,000 RNA baits. 
     42. The composition of any one of embodiments 38-41, wherein said RNA bait pool comprises overlapping RNA baits specific for at least one CRISPR RGN gene of interest and flanking sequences. 
     43. The composition of embodiment 42, wherein said flanking sequences comprise about 180 nucleotides on either side of said CRISPR RGN gene of interest. 
     44. A kit comprising an RNA bait pool comprising overlapping RNA baits specific for at least one CRISPR RGN gene of interest and a solid phase, wherein said overlapping RNA baits comprise a detectable label, and wherein a binding partner of said detectable label is attached to said solid phase. 
     45. The kit of embodiment 44, wherein said RNA baits are 50-200 nt, 70-150 nt, 100-140 nt, or 110-130 nt in length. 
     46. The kit of embodiment 44 or 45, wherein said RNA bait pool comprises overlapping RNA baits specific for at least one CRISPR RGN gene of interest and flanking sequences. 
     47. The kit of embodiment 46, wherein said flanking sequences comprise about 180 nucleotides on either side of said CRISPR RGN gene of interest. 
     The following examples are offered by way of illustration and not by way of limitation. 
     EXPERIMENTAL 
     Example 1 
     Sampling and DNA preparation: Samples were collected from diverse environmental niches on private property in NC. Bulk soil samples were suspended in liquid sodium phosphate and plated onto selective media, including: minimal media with 5 ml/L methanol as the primary carbon source, minimal media with 5% NaCl selection (high salt), minimal media incubated in anaerobic conditions, minimal media incubated in aerobic conditions, and selective media for fastidious Gram positive organisms. Genomic DNA was prepared from 400 mg of each sample with the NucleoSpin Soil preparation kit from Clontech. In an alternative method, genomic DNA was prepared with the PowerMax Soil DNA Isolation Kit from Mo Bio Laboratories. Prior to DNA extraction, intact samples were preserved as glycerol stocks for future identification of the organism bearing genes of interest and for retrieval of complete gene sequences. Yields of DNA from soil samples ranged from 66 to 622 micrograms with A260/A280 ratios ranging from 1.81 to 1.93 (Table 2). 
     
       
         
           
               
             
               
                 TABLE 2 
               
             
            
               
                   
               
               
                 Environmental sources for DNA preparations with yields 
               
               
                 and spectrophotometric quality assessments. 
               
            
           
           
               
               
               
               
               
               
            
               
                   
                   
                 DNA 
                 Concen- 
                   
                   
               
               
                   
                 Environmental Sample 
                 Yield 
                 tration 
                 A260/ 
                 A260/ 
               
               
                   
                 Description 
                 (μg) 
                 (ng/μl) 
                 A280 
                 A230 
               
               
                   
               
            
           
           
               
               
               
               
               
               
            
               
                 1 
                 Anaerobic chick feces 
                 86 
                 45 
                 1.77 
                 1.70 
               
               
                 2 
                 Rhizospheric soil 
                 622 
                 350 
                 1.85 
                 2.10 
               
               
                 3 
                 Sweet potato soil 
                 374 
                 230 
                 1.90 
                 2.10 
               
               
                 4 
                 Bulk soil 
                 345 
                 170 
                 1.88 
                 1.90 
               
               
                 5 
                 Anaerobic with methanol 
                 66 
                 35 
                 1.81 
                 1.80 
               
               
                   
                 selection from soil 
                   
                   
                   
                   
               
               
                 6 
                 Aerobic with methanol 
                 540 
                 240 
                 1.93 
                 1.90 
               
               
                   
                 selection from soil 
                   
                   
                   
                   
               
               
                 7 
                 High salt selection 
                 106 
                 60 
                 1.87 
                 1.80 
               
               
                   
                 from soil 
               
               
                   
               
            
           
         
       
     
     Oligonucleotide baits: Baits for gene capture consisted of approximately 30,000 biotinylated 120 base RNA oligonucleotides that were designed against approximately 330 genes and represent six distinct CRISPR RGN gene families of interest (Table 3). The process is used iteratively such that each subsequent round of hybridization includes baits designed to CRISPR RGN genes discovered in a previous round of gene discovery. In addition to CRISPR RGN genes of interest, additional sequences were included as positive controls (housekeeping genes) and for microbe species identification (16S rRNA). Starting points for baits were staggered at 60 bases to confer 2× coverage for each gene. Baits were synthesized at Agilent with the SureSelect technology. However, additional products for similar use are available from Agilent and other vendors including NimbleGen (SeqCap EZ), Mycroarray (MYbaits), Integrated DNA Technologies (XGen), and LC Sciences (OligoMix). 
     
       
         
           
               
             
               
                 TABLE 3 
               
             
            
               
                   
               
               
                 Gene families queried in capture reactions with 
               
               
                 the number of genes queried for each family. 
               
            
           
           
               
               
               
            
               
                   
                 Gene Family 
                 # Genes 
               
               
                   
               
            
           
           
               
               
               
            
               
                   
                 Cas9 
                 233 
               
               
                   
                 Cas12a 
                 29 
               
               
                   
                 Cas12b 
                 13 
               
               
                   
                 Cas13a 
                 12 
               
               
                   
                 Cas13b 
                 40 
               
               
                   
                 Cas13c 
                 4 
               
               
                   
                 TOTAL 
                 331 
               
               
                   
               
            
           
         
       
     
     
       
         
           
               
             
               
                 TABLE 4 
               
             
            
               
                   
               
               
                 Example baits designed against  Streptococcus pyogenes  Cas9. 
               
            
           
           
               
               
               
            
               
                 Base Pair 
                 SEQ 
                   
               
               
                 Range 
                 ID 
                 Sequence 
               
               
                   
               
            
           
           
               
               
               
            
               
                   1 . . . 120 
                 1 
                 TGGATAAGAAATACTCAATAGGCTTAGATATCGGCACAAATAGCGTCGGATGGGCGGT 
               
               
                   
                   
                 GATCACTGATGATTATAAGGTTCCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACC 
               
               
                   
                   
                 GCC 
               
               
                   
               
               
                  40 . . . 159 
                 2 
                 ATAGCGTCGGATGGGCGGTGATCACTGATGATTATAAGGTTCCGTCTAAAAAGTTCAAG 
               
               
                   
                   
                 GTTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTT 
               
               
                   
                   
                 G 
               
               
                   
               
               
                  41 . . . 160 
                 3 
                 TAGCGTCGGATGGGCGGTGATCACTGATGATTATAAGGTTCCGTCTAAAAAGTTCAAGG 
               
               
                   
                   
                 TTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTTG 
               
               
                   
                   
                 A 
               
               
                   
               
               
                  81 . . . 200 
                 4 
                 CCGTCTAAAAAGTTCAAGGTTCTGGGAAATACAGACCGCCACAGTATCAAAAAAAATCTT 
               
               
                   
                   
                 ATAGGGGCTCTTTTATTTGACAGTGGAGAGATAGCGGAAGCGACTCGTCTCAAACGGAC 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 121 . . . 240 
                 5 
                 ACAGTATCAAAAAAAATCTTATAGGGGCTCTTTTATTTGACAGTGGAGAGATAGCGGAA 
               
               
                   
                   
                 GCGACTCGTCTCAAACGGACAGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTG 
               
               
                   
                   
                 TT 
               
               
                   
               
               
                 161 . . . 280 
                 6 
                 CAGTGGAGAGATAGCGGAAGCGACTCGTCTCAAACGGACAGCTCGTAGAAGGTATACA 
               
               
                   
                   
                 CGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTA 
               
               
                   
                   
                 GA 
               
               
                   
               
               
                 200 . . . 319 
                 7 
                 AGCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTC 
               
               
                   
                   
                 AAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGT 
               
               
                   
               
               
                 201 . . . 320 
                 8 
                 GCTCGTAGAAGGTATACACGTCGGAAGAATCGTATTTGTTATCTACAGGAGATTTTTTCA 
               
               
                   
                   
                 AATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTG 
               
               
                   
               
               
                 240 . . . 359 
                 9 
                 TATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGA 
               
               
                   
                   
                 CTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGA 
               
               
                   
               
               
                 241 . . . 360 
                 10 
                 ATCTACAGGAGATTTTTTCAAATGAGATGGCGAAAGTAGATGATAGTTTCTTTCATCGAC 
               
               
                   
                   
                 TTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAA 
               
               
                   
               
               
                 280 . . . 399 
                 11 
                 ATGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATG 
               
               
                   
                   
                 AACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAA 
               
               
                   
               
               
                 281 . . . 400 
                 12 
                 TGATAGTTTCTTTCATCGACTTGAAGAGTCTTTTTTGGTGGAAGAAGACAAGAAGCATGA 
               
               
                   
                   
                 ACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAAC 
               
               
                   
               
               
                 321 . . . 440 
                 13 
                 GAAGAAGACAAGAAGCATGAACGTCATCCTATTTTTGGAAATATAGTAGATGAAGTTGC 
               
               
                   
                   
                 TTATCATGAGAAATATCCAACTATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGAT 
               
               
                   
               
               
                 361 . . . 480 
                 14 
                 ATATAGTAGATGAAGTTGCTTATCATGAGAAATATCCAACTATCTATCATCTGCGAAAAA 
               
               
                   
                   
                 AATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATA 
               
               
                   
               
               
                 401 . . . 520 
                 15 
                 TATCTATCATCTGCGAAAAAAATTGGTAGATTCTACTGATAAAGCGGATTTGCGCTTAAT 
               
               
                   
                   
                 CTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTT 
               
               
                   
               
               
                 440 . . . 559 
                 16 
                 TAAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCA 
               
               
                   
                   
                 TTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCA 
               
               
                   
               
               
                 441 . . . 560 
                 17 
                 AAAGCGGATTTGCGCTTAATCTATTTGGCCTTAGCGCATATGATTAAGTTTCGTGGTCAT 
               
               
                   
                   
                 TTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAG 
               
               
                   
               
               
                 480 . . . 599 
                 18 
                 ATGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGAT 
               
               
                   
                   
                 GTGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCT 
               
               
                   
               
               
                 481 . . . 600 
                 19 
                 TGATTAAGTTTCGTGGTCATTTTTTGATTGAGGGAGATTTAAATCCTGATAATAGTGATG 
               
               
                   
                   
                 TGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTA 
               
               
                   
               
               
                 521 . . . 640 
                 20 
                 AAATCCTGATAATAGTGATGTGGACAAACTATTTATCCAGTTGGTACAAACCTACAATCA 
               
               
                   
                   
                 ATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTCTGC 
               
               
                   
               
               
                 561 . . . 680 
                 21 
                 TTGGTACAAACCTACAATCAATTATTTGAAGAAAACCCTATTAACGCAAGTGGAGTAGAT 
               
               
                   
                   
                 GCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCT 
               
               
                   
               
               
                 601 . . . 720 
                 22 
                 TTAACGCAAGTGGAGTAGATGCTAAAGCGATTCTTTCTGCACGATTGAGTAAATCAAGA 
               
               
                   
                   
                 CGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGAAAAATGGCTTATTTGGGAA 
               
               
                   
                   
                 TC 
               
               
                   
               
               
                 641 . . . 760 
                 23 
                 ACGATTGAGTAAATCAAGACGATTAGAAAATCTCATTGCTCAGCTCCCCGGTGAGAAGA 
               
               
                   
                   
                 AAAATGGCTTATTTGGGAATCTCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATC 
               
               
                   
               
               
                 681 . . . 800 
                 24 
                 CAGCTCCCCGGTGAGAAGAAAAATGGCTTATTTGGGAATCTCATTGCTTTGTCATTGGGT 
               
               
                   
                   
                 TTGACCCCTAATTTTAAATCAAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCA 
               
               
                   
               
               
                 721 . . . 840 
                 25 
                 TCATTGCTTTGTCATTGGGTTTGACCCCTAATTTTAAATCAAATTTTGATTTGGCAGAAGA 
               
               
                   
                   
                 TGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGATTTAGATAATTTATTGGCGC 
               
               
                   
               
               
                 760 . . . 879 
                 26 
                 CAAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATG 
               
               
                   
                   
                 ATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTA 
               
               
                   
               
               
                 761 . . . 880 
                 27 
                 AAATTTTGATTTGGCAGAAGATGCTAAATTACAGCTTTCAAAAGATACTTACGATGATGA 
               
               
                   
                   
                 TTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAA 
               
               
                   
               
               
                 800 . . . 919 
                 28 
                 AAAAGATACTTACGATGATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGC 
               
               
                   
                   
                 TGATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAG 
               
               
                   
               
               
                 801 . . . 920 
                 29 
                 AAAGATACTTACGATGATGATTTAGATAATTTATTGGCGCAAATTGGAGATCAATATGCT 
               
               
                   
                   
                 GATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAGA 
               
               
                   
               
               
                 841 . . . 960 
                 30 
                 AAATTGGAGATCAATATGCTGATTTGTTTTTGGCAGCTAAGAATTTATCAGATGCTATTTT 
               
               
                   
                   
                 ACTTTCAGATATCCTAAGATTAAATAGTGAAATAACTAAGGCTCCCCTATCAGCTTCAA 
               
               
                   
               
               
                  881 . . . 1000 
                 31 
                 GAATTTATCAGATGCTATTTTACTTTCAGATATCCTAAGATTAAATAGTGAAATAACTAAG 
               
               
                   
                   
                 GCTCCCCTATCAGCTTCAATGATTAAACGCTACGATGAACATCATCAAGACTTGACTCT 
               
               
                   
               
               
                  921 . . . 1040 
                 32 
                 TTAAATAGTGAAATAACTAAGGCTCCCCTATCAGCTTCAATGATTAAACGCTACGATGAA 
               
               
                   
                   
                 CATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTAT 
               
               
                   
               
               
                  960 . . . 1079 
                 33 
                 ATGATTAAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGA 
               
               
                   
                   
                 CAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCA 
               
               
                   
               
               
                  961 . . . 1080 
                 34 
                 TGATTAAACGCTACGATGAACATCATCAAGACTTGACTCTTTTAAAAGCTTTAGTTCGAC 
               
               
                   
                   
                 AACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAG 
               
               
                   
               
               
                 1000 . . . 1119 
                 35 
                 TTTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCA 
               
               
                   
                   
                 ATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATA 
               
               
                   
               
               
                 1001 . . . 1120 
                 36 
                 TTTAAAAGCTTTAGTTCGACAACAACTTCCAGAAAAGTATAAAGAAATCTTTTTTGATCAA 
               
               
                   
                   
                 TCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAA 
               
               
                   
               
               
                 1040 . . . 1159 
                 37 
                 TAAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAG 
               
               
                   
                   
                 CTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTG 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 1041 . . . 1160 
                 38 
                 AAAGAAATCTTTTTTGATCAATCAAAAAACGGATATGCAGGTTATATTGATGGGGGAGC 
               
               
                   
                   
                 TAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGA 
               
               
                   
                   
                 G 
               
               
                   
               
               
                 1080 . . . 1199 
                 39 
                 GGTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTA 
               
               
                   
                   
                 GAAAAAATGGATGGTACTGAGGAATTATTGGCGAAACTAAATCGTGAAGATTTGCTGCG 
               
               
                   
                   
                 C 
               
               
                   
               
               
                 1081 . . . 1200 
                 40 
                 GTTATATTGATGGGGGAGCTAGCCAAGAAGAATTTTATAAATTTATCAAACCAATTTTAG 
               
               
                   
                   
                 AAAAAATGGATGGTACTGAGGAATTATTGGCGAAACTAAATCGTGAAGATTTGCTGCGC 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 1120 . . . 1239 
                 41 
                 AATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGCGAAACTA 
               
               
                   
                   
                 AATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAA 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 1121 . . . 1240 
                 42 
                 ATTTATCAAACCAATTTTAGAAAAAATGGATGGTACTGAGGAATTATTGGCGAAACTAA 
               
               
                   
                   
                 ATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAA 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 1160 . . . 1279 
                 43 
                 GGAATTATTGGCGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACA 
               
               
                   
                   
                 ACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTCTGAGAAGACAAG 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 1161 . . . 1280 
                 44 
                 GAATTATTGGCGAAACTAAATCGTGAAGATTTGCTGCGCAAGCAACGGACCTTTGACAA 
               
               
                   
                   
                 CGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATGCTATTCTGAGAAGACAAGA 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 1200 . . . 1319 
                 45 
                 AAGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCAT 
               
               
                   
                   
                 GCTATTCTGAGAAGACAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATT 
               
               
                   
               
               
                 1201 . . . 1320 
                 46 
                 AGCAACGGACCTTTGACAACGGCTCTATTCCCCATCAAATTCACTTGGGTGAGCTGCATG 
               
               
                   
                   
                 CTATTCTGAGAAGACAAGAAGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTG 
               
               
                   
               
               
                 1241 . . . 1360 
                 47 
                 TCACTTGGGTGAGCTGCATGCTATTCTGAGAAGACAAGAAGACTTTTATCCATTTTTAAA 
               
               
                   
                   
                 AGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCC 
               
               
                   
               
               
                 1280 . . . 1399 
                 48 
                 AGACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCG 
               
               
                   
                   
                 AATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCG 
               
               
                   
               
               
                 1281 . . . 1400 
                 49 
                 GACTTTTATCCATTTTTAAAAGACAATCGTGAGAAGATTGAAAAAATCTTGACTTTTCGA 
               
               
                   
                   
                 ATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGG 
               
               
                   
               
               
                 1320 . . . 1439 
                 50 
                 GAAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGT 
               
               
                   
                   
                 CGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGA 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 1321 . . . 1440 
                 51 
                 AAAAAATCTTGACTTTTCGAATTCCTTATTATGTTGGTCCATTGGCGCGTGGCAATAGTC 
               
               
                   
                   
                 GTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAA 
               
               
                   
                   
                 G 
               
               
                   
               
               
                 1360 . . . 1479 
                 52 
                 CATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATT 
               
               
                   
                   
                 ACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAA 
               
               
                   
                   
                 C 
               
               
                   
               
               
                 1361 . . . 1480 
                 53 
                 ATTGGCGCGTGGCAATAGTCGTTTTGCATGGATGACTCGGAAGTCTGAAGAAACAATTA 
               
               
                   
                   
                 CCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAAC 
               
               
                   
                   
                 G 
               
               
                   
               
               
                 1400 . . . 1519 
                 54 
                 GAAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTT 
               
               
                   
                   
                 CAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAG 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 1401 . . . 1520 
                 55 
                 AAGTCTGAAGAAACAATTACCCCATGGAATTTTGAAGAAGTTGTCGATAAAGGTGCTTC 
               
               
                   
                   
                 AGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGT 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 1440 . . . 1559 
                 56 
                 GTTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAA 
               
               
                   
                   
                 AATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTT 
               
               
                   
               
               
                 1441 . . . 1560 
                 57 
                 TTGTCGATAAAGGTGCTTCAGCTCAATCATTTATTGAACGCATGACAAACTTTGATAAAA 
               
               
                   
                   
                 ATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTTT 
               
               
                   
               
               
                 1480 . . . 1599 
                 58 
                 GCATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGC 
               
               
                   
                   
                 TTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAGGGAA 
               
               
                   
               
               
                 1481 . . . 1600 
                 59 
                 CATGACAAACTTTGATAAAAATCTTCCAAATGAAAAAGTACTACCAAAACATAGTTTGCT 
               
               
                   
                   
                 TTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTCAAATATGTTACTGAGGGAAT 
               
               
                   
               
               
                 1521 . . . 1640 
                 60 
                 CTACCAAAACATAGTTTGCTTTATGAGTATTTTACGGTTTATAACGAATTGACAAAGGTC 
               
               
                   
                   
                 AAATATGTTACTGAGGGAATGCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGC 
               
               
                   
                   
                 C 
               
               
                   
               
               
                 1561 . . . 1680 
                 61 
                 ATAACGAATTGACAAAGGTCAAATATGTTACTGAGGGAATGCGAAAACCAGCATTTCTT 
               
               
                   
                   
                 TCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACC 
               
               
                   
                   
                 G 
               
               
                   
               
               
                 1600 . . . 1719 
                 62 
                 TGCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCA 
               
               
                   
                   
                 AAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAA 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 1601 . . . 1720 
                 63 
                 GCGAAAACCAGCATTTCTTTCAGGTGAACAGAAGAAAGCCATTGTTGATTTACTCTTCAA 
               
               
                   
                   
                 AACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAAT 
               
               
                   
                   
                 G 
               
               
                   
               
               
                 1640 . . . 1759 
                 64 
                 CATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGA 
               
               
                   
                   
                 TTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATT 
               
               
                   
               
               
                 1641 . . . 1760 
                 65 
                 ATTGTTGATTTACTCTTCAAAACAAATCGAAAAGTAACCGTTAAGCAATTAAAAGAAGAT 
               
               
                   
                   
                 TATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATTT 
               
               
                   
               
               
                 1680 . . . 1799 
                 66 
                 GTTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATT 
               
               
                   
                   
                 TCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATT 
               
               
                   
               
               
                 1681 . . . 1800 
                 67 
                 TTAAGCAATTAAAAGAAGATTATTTCAAAAAAATAGAATGTTTTGATAGTGTTGAAATTT 
               
               
                   
                   
                 CAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATTA 
               
               
                   
               
               
                 1721 . . . 1840 
                 68 
                 TTTTGATAGTGTTGAAATTTCAGGAGTTGAAGATAGATTTAATGCTTCATTAGGTACCTA 
               
               
                   
                   
                 CCATGATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGA 
               
               
                   
               
               
                 1761 . . . 1880 
                 69 
                 AATGCTTCATTAGGTACCTACCATGATTTGCTAAAAATTATTAAAGATAAAGATTTTTTGG 
               
               
                   
                   
                 ATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAA 
               
               
                   
               
               
                 1801 . . . 1920 
                 70 
                 TTAAAGATAAAGATTTTTTGGATAATGAAGAAAATGAAGATATCTTAGAGGATATTGTTT 
               
               
                   
                   
                 TAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCT 
               
               
                   
                   
                 C 
               
               
                   
               
               
                 1840 . . . 1959 
                 71 
                 ATATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGG 
               
               
                   
                   
                 AAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTC 
               
               
                   
               
               
                 1841 . . . 1960 
                 72 
                 TATCTTAGAGGATATTGTTTTAACATTGACCTTATTTGAAGATAGGGAGATGATTGAGGA 
               
               
                   
                   
                 AAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCG 
               
               
                   
               
               
                 1880 . . . 1999 
                 73 
                 AGATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGG 
               
               
                   
                   
                 TGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGA 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 1881 . . . 2000 
                 74 
                 GATAGGGAGATGATTGAGGAAAGACTTAAAACATATGCTCACCTCTTTGATGATAAGGT 
               
               
                   
                   
                 GATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGAT 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 1920 . . . 2039 
                 75 
                 CACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGG 
               
               
                   
                   
                 ACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATT 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 1921 . . . 2040 
                 76 
                 ACCTCTTTGATGATAAGGTGATGAAACAGCTTAAACGTCGCCGTTATACTGGTTGGGGA 
               
               
                   
                   
                 CGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTA 
               
               
                   
                   
                 G 
               
               
                   
               
               
                 1960 . . . 2079 
                 77 
                 GCCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAG 
               
               
                   
                   
                 CAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTA 
               
               
                   
               
               
                 1961 . . . 2080 
                 78 
                 CCGTTATACTGGTTGGGGACGTTTGTCTCGAAAATTGATTAATGGTATTAGGGATAAGCA 
               
               
                   
                   
                 ATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTAT 
               
               
                   
               
               
                 2000 . . . 2119 
                 79 
                 TAATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGG 
               
               
                   
                   
                 TTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGA 
               
               
                   
               
               
                 2001 . . . 2120 
                 80 
                 AATGGTATTAGGGATAAGCAATCTGGCAAAACAATATTAGATTTTTTGAAATCAGATGGT 
               
               
                   
                   
                 TTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGAC 
               
               
                   
               
               
                 2040 . . . 2159 
                 81 
                 GATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATA 
               
               
                   
                   
                 GTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTA 
               
               
                   
               
               
                 2041 . . . 2160 
                 82 
                 ATTTTTTGAAATCAGATGGTTTTGCCAATCGCAATTTTATGCAGCTGATCCATGATGATAG 
               
               
                   
                   
                 TTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTAC 
               
               
                   
               
               
                 2080 . . . 2199 
                 83 
                 TGCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTG 
               
               
                   
                   
                 TCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATT 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 2081 . . . 2200 
                 84 
                 GCAGCTGATCCATGATGATAGTTTGACATTTAAAGAAGACATTCAAAAAGCACAAGTGT 
               
               
                   
                   
                 CTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTA 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 2120 . . . 2239 
                 85 
                 CATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTT 
               
               
                   
                   
                 AGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATT 
               
               
                   
               
               
                 2121 . . . 2240 
                 86 
                 ATTCAAAAAGCACAAGTGTCTGGACAAGGCGATAGTTTACATGAACATATTGCAAATTTA 
               
               
                   
                   
                 GCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTG 
               
               
                   
               
               
                 2160 . . . 2279 
                 87 
                 CATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACT 
               
               
                   
                   
                 GTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGT 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 2161 . . . 2280 
                 88 
                 ATGAACATATTGCAAATTTAGCTGGTAGCCCTGCTATTAAAAAAGGTATTTTACAGACTG 
               
               
                   
                   
                 TAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTT 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 2200 . . . 2319 
                 89 
                 AAAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGG 
               
               
                   
                   
                 CATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGG 
               
               
                   
                   
                 CC 
               
               
                   
               
               
                 2201 . . . 2320 
                 90 
                 AAAAGGTATTTTACAGACTGTAAAAGTTGTTGATGAATTGGTCAAAGTAATGGGGCGGC 
               
               
                   
                   
                 ATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGGC 
               
               
                   
                   
                 CA 
               
               
                   
               
               
                 2240 . . . 2359 
                 91 
                 GGTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAA 
               
               
                   
                   
                 AATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGTGAGCGTATGAAACGTATTGAAG 
               
               
                   
                   
                 AAGG 
               
               
                   
               
               
                 2241 . . . 2360 
                 92 
                 GTCAAAGTAATGGGGCGGCATAAGCCAGAAAATATCGTTATTGAAATGGCACGTGAAA 
               
               
                   
                   
                 ATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGTGAGCGTATGAAACGTATTGAAGA 
               
               
                   
                   
                 AGGT 
               
               
                   
               
               
                 2281 . . . 2400 
                 93 
                 TTGAAATGGCACGTGAAAATCAGACAACTCAAAAGGGCCAGAAAAATTCGCGTGAGCG 
               
               
                   
                   
                 TATGAAACGTATTGAAGAAGGTATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATC 
               
               
                   
                   
                 CTG 
               
               
                   
               
               
                 2321 . . . 2440 
                 94 
                 GAAAAATTCGCGTGAGCGTATGAAACGTATTGAAGAAGGTATCAAAGAATTAGGAAGT 
               
               
                   
                   
                 CAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTC 
               
               
                   
                   
                 TA 
               
               
                   
               
               
                 2361 . . . 2480 
                 95 
                 ATCAAAGAATTAGGAAGTCAGATTCTTAAAGAGCATCCTGTTGAAAATACTCAATTGCAA 
               
               
                   
                   
                 AATGAAAAGCTCTATCTCTATTATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGA 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 2401 . . . 2520 
                 96 
                 TTGAAAATACTCAATTGCAAAATGAAAAGCTCTATCTCTATTATCTCCAAAATGGAAGAG 
               
               
                   
                   
                 ACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAGTGATTATGATGTCGATCACA 
               
               
                   
               
               
                 2441 . . . 2560 
                 97 
                 TTATCTCCAAAATGGAAGAGACATGTATGTGGACCAAGAATTAGATATTAATCGTTTAAG 
               
               
                   
                   
                 TGATTATGATGTCGATCACATTGTTCCACAAAGTTTCATTAAAGACGATTCAATAGACAA 
               
               
                   
               
               
                 2481 . . . 2600 
                 98 
                 TTAGATATTAATCGTTTAAGTGATTATGATGTCGATCACATTGTTCCACAAAGTTTCATTA 
               
               
                   
                   
                 AAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCG 
               
               
                   
               
               
                 2483 . . . 2602 
                 99 
                 AGATATTAATCGTTTAAGTGATTATGATGTCGATCACATTGTTCCACAAAGTTTCATTAAA 
               
               
                   
                   
                 GACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCGGA 
               
               
                   
               
               
                 2521 . . . 2640 
                 100 
                 TTGTTCCACAAAGTTTCATTAAAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTG 
               
               
                   
                   
                 ATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAA 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 2523 . . . 2642 
                 101 
                 GTTCCACAAAGTTTCATTAAAGACGATTCAATAGACAATAAGGTCTTAACGCGTTCTGAT 
               
               
                   
                   
                 AAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAA 
               
               
                   
                   
                 AC 
               
               
                   
               
               
                 2561 . . . 2680 
                 102 
                 TAAGGTCTTAACGCGTTCTGATAAAAATCGTGGTAAATCGGATAACGTTCCAAGTGAAG 
               
               
                   
                   
                 AAGTAGTCAAAAAGATGAAAAACTATTGGAGACAACTTCTAAATGCCAAGTTAATCACTC 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 2601 . . . 2720 
                 103 
                 GATAACGTTCCAAGTGAAGAAGTAGTCAAAAAGATGAAAAACTATTGGAGACAACTTCT 
               
               
                   
                   
                 AAATGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAG 
               
               
                   
                   
                 GT 
               
               
                   
               
               
                 2641 . . . 2760 
                 104 
                 ACTATTGGAGACAACTTCTAAATGCCAAGTTAATCACTCAACGTAAGTTTGATAATTTAA 
               
               
                   
                   
                 CGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAA 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 2681 . . . 2800 
                 105 
                 ACGTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAG 
               
               
                   
                   
                 CTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAA 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 2683 . . . 2802 
                 106 
                 GTAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCT 
               
               
                   
                   
                 GGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATT 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 2684 . . . 2803 
                 107 
                 TAAGTTTGATAATTTAACGAAAGCTGAACGTGGAGGTTTGAGTGAACTTGATAAAGCTG 
               
               
                   
                   
                 GTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTT 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 2721 . . . 2840 
                 108 
                 TTGAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATC 
               
               
                   
                   
                 ACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGA 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 2723 . . . 2842 
                 109 
                 GAGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCAC 
               
               
                   
                   
                 TAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATA 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 2724 . . . 2843 
                 110 
                 AGTGAACTTGATAAAGCTGGTTTTATCAAACGCCAATTGGTTGAAACTCGCCAAATCACT 
               
               
                   
                   
                 AAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATAA 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 2761 . . . 2880 
                 111 
                 TGGTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATA 
               
               
                   
                   
                 CTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTA 
               
               
                   
               
               
                 2763 . . . 2882 
                 112 
                 GTTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACT 
               
               
                   
                   
                 AAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAA 
               
               
                   
               
               
                 2764 . . . 2883 
                 113 
                 TTGAAACTCGCCAAATCACTAAGCATGTGGCACAAATTTTGGATAGTCGCATGAATACTA 
               
               
                   
                   
                 AATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAAT 
               
               
                   
               
               
                 2801 . . . 2920 
                 114 
                 TTTGGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAA 
               
               
                   
                   
                 AGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAA 
               
               
                   
               
               
                 2803 . . . 2922 
                 115 
                 TGGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAA 
               
               
                   
                   
                 GTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAG 
               
               
                   
               
               
                 2804 . . . 2923 
                 116 
                 GGATAGTCGCATGAATACTAAATACGATGAAAATGATAAACTTATTCGAGAGGTTAAAG 
               
               
                   
                   
                 TGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGT 
               
               
                   
               
               
                 2841 . . . 2960 
                 117 
                 AAACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAA 
               
               
                   
                   
                 AAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCG 
               
               
                   
               
               
                 2843 . . . 2962 
                 118 
                 ACTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAA 
               
               
                   
                   
                 GATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTA 
               
               
                   
               
               
                 2844 . . . 2963 
                 119 
                 CTTATTCGAGAGGTTAAAGTGATTACCTTAAAATCTAAATTAGTTTCTGACTTCCGAAAA 
               
               
                   
                   
                 GATTTCCAATTCTATAAAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTAT 
               
               
                   
               
               
                 2880 . . . 2999 
                 120 
                 AAATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATT 
               
               
                   
                   
                 ACCATCATGCCCATGATGCGTATCTTAATGCCGTCGTTGGAACTGCTTTGATTAAGAAA 
               
               
                   
               
               
                 2881 . . . 3000 
                 121 
                 AATTAGTTTCTGACTTCCGAAAAGATTTCCAATTCTATAAAGTACGTGAGATTAACAATTA 
               
               
                   
                   
                 CCATCATGCCCATGATGCGTATCTTAATGCCGTCGTTGGAACTGCTTTGATTAAGAAAT 
               
               
                   
               
               
                 2920 . . . 3039 
                 122 
                 AAGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTATCTTAATGCCGTCGTTG 
               
               
                   
                   
                 GAACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATA 
               
               
                   
               
               
                 2921 . . . 3040 
                 123 
                 AGTACGTGAGATTAACAATTACCATCATGCCCATGATGCGTATCTTAATGCCGTCGTTGG 
               
               
                   
                   
                 AACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATAA 
               
               
                   
               
               
                 2961 . . . 3080 
                 124 
                 TATCTTAATGCCGTCGTTGGAACTGCTTTGATTAAGAAATATCCAAAACTTGAATCGGAG 
               
               
                   
                   
                 TTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAATGCTTGCTAAGTCTGAGCAG 
               
               
                   
               
               
                 3001 . . . 3120 
                 125 
                 ATCCAAAACTTGAATCGGAGTTTGTCTATGGTGATTATAAAGTTTATGATGTTCGTAAAA 
               
               
                   
                   
                 TGCTTGCTAAGTCTGAGCAGGAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTA 
               
               
                   
               
               
                 3041 . . . 3160 
                 126 
                 AGTTTATGATGTTCGTAAAATGCTTGCTAAGTCTGAGCAGGAAATAGGCAAAGCAACCG 
               
               
                   
                   
                 CAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAA 
               
               
                   
               
               
                 3080 . . . 3199 
                 127 
                 GGAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAA 
               
               
                   
                   
                 AACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATG 
               
               
                   
                   
                 G 
               
               
                   
               
               
                 3081 . . . 3200 
                 128 
                 GAAATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAA 
               
               
                   
                   
                 CAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGG 
               
               
                   
               
               
                 3084 . . . 3203 
                 129 
                 ATAGGCAAAGCAACCGCAAAATATTTCTTTTACTCTAATATCATGAACTTCTTCAAAACAG 
               
               
                   
                   
                 AAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAA 
               
               
                   
               
               
                 3120 . . . 3239 
                 130 
                 AATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGC 
               
               
                   
                   
                 CCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTT 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 3121 . . . 3240 
                 131 
                 ATATCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCC 
               
               
                   
                   
                 CTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTT 
               
               
                   
                   
                 G 
               
               
                   
               
               
                 3124 . . . 3243 
                 132 
                 TCATGAACTTCTTCAAAACAGAAATTACACTTGCAAATGGAGAGATTCGCAAACGCCCTC 
               
               
                   
                   
                 TAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGC 
               
               
                   
                   
                 CA 
               
               
                   
               
               
                 3160 . . . 3279 
                 133 
                 ATGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTC 
               
               
                   
                   
                 TGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAA 
               
               
                   
                   
                 TA 
               
               
                   
               
               
                 3161 . . . 3280 
                 134 
                 TGGAGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCT 
               
               
                   
                   
                 GGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAAT 
               
               
                   
                   
                 AT 
               
               
                   
               
               
                 3164 . . . 3283 
                 135 
                 AGAGATTCGCAAACGCCCTCTAATCGAAACTAATGGGGAAACTGGAGAAATTGTCTGGG 
               
               
                   
                   
                 ATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATT 
               
               
                   
                   
                 GT 
               
               
                   
               
               
                 3200 . . . 3319 
                 136 
                 GGAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTA 
               
               
                   
                   
                 TTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTC 
               
               
                   
                   
                 CAA 
               
               
                   
               
               
                 3201 . . . 3320 
                 137 
                 GAAACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATT 
               
               
                   
                   
                 GTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCA 
               
               
                   
                   
                 AG 
               
               
                   
               
               
                 3204 . . . 3323 
                 138 
                 ACTGGAGAAATTGTCTGGGATAAAGGGCGAGATTTTGCCACAGTGCGCAAAGTATTGTC 
               
               
                   
                   
                 CATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGG 
               
               
                   
                   
                 AG 
               
               
                   
               
               
                 3240 . . . 3359 
                 139 
                 GCCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGT 
               
               
                   
                   
                 ACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTA 
               
               
                   
                   
                 TT 
               
               
                   
               
               
                 3241 . . . 3360 
                 140 
                 CCACAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTA 
               
               
                   
                   
                 CAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTAT 
               
               
                   
                   
                 TG 
               
               
                   
               
               
                 3244 . . . 3363 
                 141 
                 CAGTGCGCAAAGTATTGTCCATGCCCCAAGTCAATATTGTCAAGAAAACAGAAGTACAG 
               
               
                   
                   
                 ACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCT 
               
               
                   
                   
                 C 
               
               
                   
               
               
                 3280 . . . 3399 
                 142 
                 TTGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAA 
               
               
                   
                   
                 AGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGG 
               
               
                   
                   
                 TT 
               
               
                   
               
               
                 3281 . . . 3400 
                 143 
                 TGTCAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAA 
               
               
                   
                   
                 GAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGT 
               
               
                   
                   
                 TT 
               
               
                   
               
               
                 3284 . . . 3403 
                 144 
                 CAAGAAAACAGAAGTACAGACAGGCGGATTCTCCAAGGAGTCAATTTTACCAAAAAGAA 
               
               
                   
                   
                 ATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTT 
               
               
                   
                   
                 GA 
               
               
                   
               
               
                 3320 . . . 3439 
                 145 
                 GGAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGG 
               
               
                   
                   
                 ATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTG 
               
               
                   
                   
                 C 
               
               
                   
               
               
                 3321 . . . 3440 
                 146 
                 GAGTCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGA 
               
               
                   
                   
                 TCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGC 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 3324 . . . 3443 
                 147 
                 TCAATTTTACCAAAAAGAAATTCGGACAAGCTTATTGCTCGTAAAAAAGACTGGGATCCA 
               
               
                   
                   
                 AAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAG 
               
               
                   
               
               
                 3360 . . . 3479 
                 148 
                 GCTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGC 
               
               
                   
                   
                 TTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCG 
               
               
                   
                   
                 TT 
               
               
                   
               
               
                 3361 . . . 3480 
                 149 
                 CTCGTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCT 
               
               
                   
                   
                 TATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGT 
               
               
                   
                   
                 TA 
               
               
                   
               
               
                 3364 . . . 3483 
                 150 
                 GTAAAAAAGACTGGGATCCAAAAAAATATGGTGGTTTTGATAGTCCAACGGTAGCTTAT 
               
               
                   
                   
                 TCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAA 
               
               
                   
                   
                 AG 
               
               
                   
               
               
                 3401 . . . 3520 
                 151 
                 TGATAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAAT 
               
               
                   
                   
                 CGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCC 
               
               
                   
                   
                 TT 
               
               
                   
               
               
                 3404 . . . 3523 
                 152 
                 TAGTCCAACGGTAGCTTATTCAGTCCTAGTGGTTGCTAAGGTGGAAAAAGGGAAATCGA 
               
               
                   
                   
                 AGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTT 
               
               
                   
                   
                 GA 
               
               
                   
               
               
                 3441 . . . 3560 
                 153 
                 AAGGTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCA 
               
               
                   
                   
                 CAATTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGAT 
               
               
                   
                   
                 AT 
               
               
                   
               
               
                 3444 . . . 3563 
                 154 
                 GTGGAAAAAGGGAAATCGAAGAAGTTAAAATCCGTTAAAGAGTTACTAGGGATCACAA 
               
               
                   
                   
                 TTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATA 
               
               
                   
                   
                 AG 
               
               
                   
               
               
                 3481 . . . 3600 
                 155 
                 AAGAGTTACTAGGGATCACAATTATGGAAAGAAGTTCCTTTGAAAAAAATCCGATTGAC 
               
               
                   
                   
                 TTTTTAGAAGCTAAAGGATATAAGGAAGTTAGAAAAGACTTAATCATTAAACTACCTAAA 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 3521 . . . 3640 
                 156 
                 TGAAAAAAATCCGATTGACTTTTTAGAAGCTAAAGGATATAAGGAAGTTAGAAAAGACT 
               
               
                   
                   
                 TAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGC 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 3561 . . . 3680 
                 157 
                 AAGGAAGTTAGAAAAGACTTAATCATTAAACTACCTAAATATAGTCTTTTTGAGTTAGAA 
               
               
                   
                   
                 AACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGG 
               
               
                   
                   
                 CT 
               
               
                   
               
               
                 3601 . . . 3720 
                 158 
                 ATAGTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTA 
               
               
                   
                   
                 CAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGT 
               
               
                   
                   
                 C 
               
               
                   
               
               
                 3604 . . . 3723 
                 159 
                 GTCTTTTTGAGTTAGAAAACGGTCGTAAACGGATGCTGGCTAGTGCCGGAGAATTACAA 
               
               
                   
                   
                 AAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCAT 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 3641 . . . 3760 
                 160 
                 GGCTAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTG 
               
               
                   
                   
                 AATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAA 
               
               
                   
                   
                 CA 
               
               
                   
               
               
                 3644 . . . 3763 
                 161 
                 TAGTGCCGGAGAATTACAAAAAGGAAATGAGCTGGCTCTGCCAAGCAAATATGTGAATT 
               
               
                   
                   
                 TTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAA 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 3680 . . . 3799 
                 162 
                 TCTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGG 
               
               
                   
                   
                 TAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAG 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 3681 . . . 3800 
                 163 
                 CTGCCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGT 
               
               
                   
                   
                 AGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGA 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 3684 . . . 3803 
                 164 
                 CCAAGCAAATATGTGAATTTTTTATATTTAGCTAGTCATTATGAAAAGTTGAAGGGTAGT 
               
               
                   
                   
                 CCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGA 
               
               
                   
                   
                 G 
               
               
                   
               
               
                 3720 . . . 3839 
                 165 
                 CATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGA 
               
               
                   
                   
                 GCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGT 
               
               
                   
                   
                 T 
               
               
                   
               
               
                 3721 . . . 3840 
                 166 
                 ATTATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAG 
               
               
                   
                   
                 CAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTT 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 3724 . . . 3843 
                 167 
                 ATGAAAAGTTGAAGGGTAGTCCAGAAGATAACGAACAAAAACAATTGTTTGTGGAGCA 
               
               
                   
                   
                 GCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTAT 
               
               
                   
                   
                 TT 
               
               
                   
               
               
                 3760 . . . 3879 
                 168 
                 AAAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCA 
               
               
                   
                   
                 GTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCAT 
               
               
                   
               
               
                 3761 . . . 3880 
                 169 
                 AAAACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCA 
               
               
                   
                   
                 GTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATA 
               
               
                   
               
               
                 3764 . . . 3883 
                 170 
                 ACAATTGTTTGTGGAGCAGCATAAGCATTATTTAGATGAGATTATTGAGCAAATCAGTGA 
               
               
                   
                   
                 ATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAA 
               
               
                   
               
               
                 3800 . . . 3919 
                 171 
                 TGAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTT 
               
               
                   
                   
                 AGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAG 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 3801 . . . 3920 
                 172 
                 GAGATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTA 
               
               
                   
                   
                 GATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGA 
               
               
                   
                   
                 A 
               
               
                   
               
               
                 3804 . . . 3923 
                 173 
                 ATTATTGAGCAAATCAGTGAATTTTCTAAGCGTGTTATTTTAGCAGATGCCAATTTAGATA 
               
               
                   
                   
                 AAGTTCTTAGTGCATATAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAAT 
               
               
                   
               
               
                 3840 . . . 3959 
                 174 
                 ATTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAA 
               
               
                   
                   
                 CCAATACGTGAACAAGCAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCT 
               
               
                   
               
               
                 3841 . . . 3960 
                 175 
                 TTTTAGCAGATGCCAATTTAGATAAAGTTCTTAGTGCATATAACAAACATAGAGACAAAC 
               
               
                   
                   
                 CAATACGTGAACAAGCAGAAAATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTC 
               
               
                   
               
               
                 3881 . . . 4000 
                 176 
                 TAACAAACATAGAGACAAACCAATACGTGAACAAGCAGAAAATATTATTCATTTATTTAC 
               
               
                   
                   
                 GTTGACGAATCTTGGAGCTCCCACTGCTTTTAAATATTTTGATACAACAATTGATCGTAA 
               
               
                   
               
               
                 3921 . . . 4040 
                 177 
                 AATATTATTCATTTATTTACGTTGACGAATCTTGGAGCTCCCACTGCTTTTAAATATTTTGA 
               
               
                   
                   
                 TACAACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTTTT 
               
               
                   
               
               
                 3961 . . . 4080 
                 178 
                 CCACTGCTTTTAAATATTTTGATACAACAATTGATCGTAAACGATATACGTCTACAAAAGA 
               
               
                   
                   
                 AGTTTTAGATGCCACTTTTATCCATCAATCCATCACTGGTCTTTATGAAACACGCATTG 
               
               
                   
               
               
                 3987 . . . 4106 
                 179 
                 ACAATTGATCGTAAACGATATACGTCTACAAAAGAAGTTTTAGATGCCACTTTTATCCATC 
               
               
                   
                   
                 AATCCATCACTGGTCTTTATGAAACACGCATTGATTTGAGTCAGCTAGGAGGTGACTGA 
               
               
                   
               
            
           
         
       
     
     Gene capture reactions: 3 μg of DNA was used as starting material for the procedure. DNA shearing, capture, post-capture washing and gene amplification are performed in accordance with Agilent SureSelect specifications. Throughout the procedure, DNA is purified with the Agencourt AMPure XP beads, and DNA quality was evaluated with the Agilent TapeStation. Briefly, DNA is sheared to an approximate length of 800 bp using a Covaris Focused-ultrasonicator. In an alternative method, DNA is sheared to lengths from about 400 to about 2000 bp, including about 500 bp, about 600 bp, about 700 bp, about 900 bp, about 1000 bp, about 1200 bp, about 1400 bp, about 1600 bp, about 1800 bp. The Agilent SureSelect Library Prep Kit was used to repair ends, add A bases, ligate the paired-end adaptor and amplify the adaptor-ligated fragments. Prepped DNA samples were lyophilized to contain 750 ng in 3.4 μL and mixed with Agilent SureSelect Hybridization buffers, Capture Library Mix and Block Mix. Hybridization was performed for at least 16 hours at 65° C. In an alternative method, hybridization is performed at a lower temperature (55° C.). DNAs hybridized to biotinylated baits were precipitated with Dynabeads MyOne Streptavidin T1 magnetic beads and washed with SureSelect Binding and Wash Buffers. Captured DNAs were PCR-amplified to add index tags and pooled for multiplexed sequencing. 
     Genomic DNA libraries were generated by adding a predetermined amount of sample DNA to, for example, the Paired End Sample prep kit PE-102-1001 (ILLUMINA, Inc.) following manufacturer&#39;s protocol. Briefly, DNA fragments were generated by random shearing and conjugated to a pair of oligonucleotides in a forked adaptor configuration. The ligated products are amplified using two oligonucleotide primers, resulting in double-stranded blunt-ended products having a different adaptor sequence on either end. The libraries once generated are applied to a flow cell for cluster generation. 
     Ousters were formed prior to sequencing using the TruSeq PE v3 cluster kit (ILLUMINA, Inc.) following manufacturer&#39;s instructions. Briefly, products from a DNA library preparation were denatured and single strands annealed to complementary oligonucleotides on the flow cell surface. A new strand was copied from the original strand in an extension reaction and the original strand was removed by denaturation. The adaptor sequence of the copied strand was annealed to a surface-bound complementary oligonucleotide, forming a bridge and generating a new site for synthesis of a second strand. Multiple cycles of annealing, extension and denaturation in isothermal conditions resulted in growth of clusters, each approximately 1 μm in physical diameter. 
     The DNA in each cluster was linearized by cleavage within one adaptor sequence and denatured, generating single-stranded template for sequencing by synthesis (SBS) to obtain a sequence read. To perform paired-read sequencing, the products of read 1 can be removed by denaturation, the template was used to generate a bridge, the second strand was re-synthesized and the opposite strand was cleaved to provide the template for the second read. Sequencing was performed using the ILLUMINA, Inc. V4 SBS kit with 100 base paired-end reads on the HiSeq 2000. Briefly, DNA templates were sequenced by repeated cycles of polymerase-directed single base extension. To ensure base-by-base nucleotide incorporation in a stepwise manner, a set of four reversible terminators, A, C, G, and T, each labeled with a different removable fluorophore, was used. The use of modified nucleotides allowed incorporation to be driven essentially to completion without risk of over-incorporation. It also enabled addition of all four nucleotides simultaneously minimizing risk of misincorporation. After each cycle of incorporation, the identity of the inserted base was determined by laser-induced excitation of the fluorophores and fluorescence imaging was recorded. The fluorescent dye and linker were removed to regenerate an available group ready for the next cycle of nucleotide addition. The HiSeq sequencing instrument is designed to perform multiple cycles of sequencing chemistry and imaging to collect sequence data automatically from each cluster on the surface of each lane of an eight-lane flow cell. 
     Bioinformatics: Sequences were assembled using the CLC Bio suite of bioinformatics tools. The presence of CRISPR RGN genes of interest (Table 3) was determined by BLAST query against a database of those genes of interest. Diversity of organisms present in the sample can be evaluated from 16S identifications. To assess the capacity of this approach for new gene discovery, translations of assembled genes were BLASTed against protein sequences published in public databases including NCBI and PatentLens. The lowest % identity to a gene was 69.98%. Example genes that were captured and sequenced with this method are shown in Table 5. 
     
       
         
           
               
             
               
                 TABLE 5 
               
             
            
               
                   
               
               
                 Examples of homologs to targeted genes 
               
               
                 captured and sequenced with the method. 
               
            
           
           
               
               
               
               
            
               
                   
                   
                 % 
                 Hit Length 
               
               
                 Sequence 
                 Closest Homolog 
                 Identity 
                 (AA) 
               
               
                   
               
            
           
           
               
               
               
               
            
               
                 contig_10 - ORF 12 
                 WP_087094968.1 
                 70.65 
                 1063 
               
               
                 contig_11 - ORF 15 
                 WP_048723014.1 
                 69.98 
                 1076 
               
               
                 contig_18 - ORF 2 
                 WP_023519017.1 
                 97.74 
                 1330 
               
               
                 contig_4110 - ORF 21 
                 WP_065399661.1 
                 95.05 
                 1090 
               
               
                 contig_577 - ORF 9 
                 WP_076394715.1 
                 88.42 
                 838 
               
               
                 contig_18 - ORF 15 
                 WP_098836991.1 
                 96.35 
                 1068 
               
               
                 contig_189 - ORF 15 
                 WP_098135402.1 
                 93.09 
                 1071 
               
               
                 contig_28 - ORF 21 
                 KXY52240.1 
                 96.25 
                 1068 
               
               
                 contig_5 - ORF 17 
                 WP_098519598.1 
                 94.56 
                 1067 
               
               
                 contig_78 - ORF 12 
                 WP_086390158.1 
                 94.67 
                 1069 
               
               
                 contig_17 - ORF 28 
                 WP_065399661.1 
                 95.69 
                 1438 
               
               
                 contig_53 - ORF 1 
                 WP_098149203.1 
                 88.13 
                 1070 
               
               
                 contig_1474 - ORF 1 
                 WP_003343632.1 
                 98.63 
                 1092 
               
               
                 contig_226 - ORF 2 
                 WP_065399661.1 
                 95.69 
                 1438 
               
               
                 contig_433 - ORF 20 
                 WP_121730027.1 
                 84.99 
                 1039 
               
               
                 contig_697 - ORF 2 
                 WP_098149203.1 
                 87.94 
                 1070 
               
               
                 contig_1957 - ORF 1 
                 WP_002413717.1 
                 99.85 
                 1337 
               
               
                   
               
            
           
         
       
     
     Sequences of the homologs identified in Table 5 were also analyzed for the presence of domains present in known CRISPR RGN genes, including but not limited to RuvC domains, HNH domains, and PAM interacting domains. Results of this analysis are shown in Table 6. 
     
       
         
           
               
             
               
                 TABLE 6 
               
             
            
               
                   
               
               
                 Protein domains present in captured homologs. 
               
            
           
           
               
               
               
               
            
               
                   
                   
                   
                 Domain 
               
               
                   
                   
                   
                 Location in 
               
               
                 Sequence 
                 Domain Name 
                 Database 
                 Protein 
               
               
                   
               
               
                 contig_10 - ORF 12 
                 Cas9_a 
                 Pfam 
                 237 . . . 301 
               
               
                 contig_10 - ORF 12 
                 HNH_4 
                 Pfam 
                 568 . . . 622 
               
               
                 contig_10 - ORF 12 
                 HNH_CAS9 
                 PROSITE_PROFILES 
                 515 . . . 670 
               
               
                 contig_10 - ORF 12 
                 RuvC_III 
                 Pfam 
                 661 . . . 720 
               
               
                 contig_10 - ORF 12 
                 TIGR01865 
                 TIGRFAM 
                  2 . . . 746 
               
               
                 contig_11 - ORF 15 
                 Cas9_a 
                 Pfam 
                 238 . . . 300 
               
               
                 contig_11 - ORF 15 
                 HNH_4 
                 Pfam 
                 568 . . . 622 
               
               
                 contig_11 - ORF 15 
                 HNH_CAS9 
                 PROSITE_PROFILES 
                 515 . . . 670 
               
               
                 contig_11 - ORF 15 
                 RuvC_III 
                 Pfam 
                 661 . . . 782 
               
               
                 contig_11 - ORF 15 
                 TIGR01865 
                 TIGRFAM 
                  3 . . . 743 
               
               
                 contig_18 - ORF 2 
                 Cas9-BH 
                 Pfam 
                  70 . . . 102 
               
               
                 contig_18 - ORF 2 
                 Cas9_PI 
                 Pfam 
                 1081 . . . 1325 
               
               
                 contig_18 - ORF 2 
                 Cas9_REC 
                 Pfam 
                 189 . . . 720 
               
               
                 contig_18 - ORF 2 
                 HNH_4 
                 Pfam 
                 826 . . . 876 
               
               
                 contig_18 - ORF 2 
                 HNH_CAS9 
                 PROSITE_PROFILES 
                 769 . . . 923 
               
               
                 contig_18 - ORF 2 
                 TIGR01865 
                 TIGRFAM 
                  12 . . . 1040 
               
               
                 contig_4110 - ORF 21 
                 HNH_4 
                 Pfam 
                 479 . . . 529 
               
               
                 contig_4110 - ORF 21 
                 HNH_CAS9 
                 PROSITE_PROFILES 
                 418 . . . 590 
               
               
                 contig_4110 - ORF 21 
                 RuvC_III 
                 Pfam 
                 580 . . . 786 
               
               
                 contig_577 - ORF 9 
                 HNH_4 
                 Pfam 
                 200 . . . 252 
               
               
                 contig_577 - ORF 9 
                 HNH_CAS9 
                 PROSITE_PROFILES 
                 145 . . . 304 
               
               
                 contig_577 - ORF 9 
                 RuvC_III 
                 Pfam 
                 294 . . . 472 
               
               
                 contig_18 - ORF 15 
                 HNH_4 
                 Pfam 
                 560 . . . 614 
               
               
                 contig_18 - ORF 15 
                 HNH_CAS9 
                 PROSITE_PROFILES 
                 509 . . . 662 
               
               
                 contig_18 - ORF 15 
                 RuvC_III 
                 Pfam 
                 654 . . . 712 
               
               
                 contig_18 - ORF 15 
                 TIGR01865 
                 TIGRFAM 
                  3 . . . 747 
               
               
                 contig_189 - ORF 15 
                 HNH_4 
                 Pfam 
                 574 . . . 636 
               
               
                 contig_189 - ORF 15 
                 HNH_CAS9 
                 PROSITE_PROFILES 
                 523 . . . 685 
               
               
                 contig_189 - ORF 15 
                 RuvC_III 
                 Pfam 
                 678 . . . 776 
               
               
                 contig_189 - ORF 15 
                 TIGR01865 
                 TIGRFAM 
                  5 . . . 773 
               
               
                 contig_28 - ORF 21 
                 HNH_4 
                 Pfam 
                 566 . . . 620 
               
               
                 contig_28 - ORF 21 
                 HNH_CAS9 
                 PROSITE_PROFILES 
                 515 . . . 668 
               
               
                 contig_28 - ORF 21 
                 RuvC_III 
                 Pfam 
                 660 . . . 776 
               
               
                 contig_28 - ORF 21 
                 TIGR01865 
                 TIGRFAM 
                  8 . . . 755 
               
               
                 contig_5 - ORF 17 
                 Cytoplasmic domain 
                 PHOBIUS 
                 1 . . . 6 
               
               
                 contig_5 - ORF 17 
                 HNH_4 
                 Pfam 
                 566 . . . 620 
               
               
                 contig_5 - ORF 17 
                 HNH_CAS9 
                 PROSITE_PROFILES 
                 515 . . . 668 
               
               
                 contig_5 - ORF 17 
                 Non cytoplasmic domain 
                 PHOBIUS 
                  26 . . . 1073 
               
               
                 contig_5 - ORF 17 
                 RuvC_III 
                 Pfam 
                 660 . . . 759 
               
               
                 contig_5 - ORF 17 
                 TIGR01865 
                 TIGRFAM 
                  8 . . . 754 
               
               
                 contig_5 - ORF 17 
                 Transmembrane region 
                 PHOBIUS 
                  7 . . . 25 
               
               
                 contig_78 - ORF 12 
                 HNH_4 
                 Pfam 
                 559 . . . 613 
               
               
                 contig_78 - ORF 12 
                 HNH_CAS9 
                 PROSITE_PROFILES 
                 508 . . . 662 
               
               
                 contig_78 - ORF 12 
                 TIGR01865 
                 TIGRFAM 
                  3 . . . 741 
               
               
                 contig_17 - ORF 28 
                 Cas9-BH 
                 Pfam 
                 62 . . . 96 
               
               
                 contig_17 - ORF 28 
                 HNH_4 
                 Pfam 
                 829 . . . 879 
               
               
                 contig_17 - ORF 28 
                 HNH_CAS9 
                 PROSITE_PROFILES 
                 768 . . . 940 
               
               
                 contig_17 - ORF 28 
                 RuvC_III 
                 Pfam 
                  930 . . . 1136 
               
               
                 contig_53 - ORF 1 
                 HNH_4 
                 Pfam 
                 574 . . . 636 
               
               
                 contig_53 - ORF 1 
                 HNH_CAS9 
                 PROSITE_PROFILES 
                 523 . . . 685 
               
               
                 contig_53 - ORF 1 
                 RuvC_III 
                 Pfam 
                 680 . . . 739 
               
               
                 contig_53 - ORF 1 
                 TIGR01865 
                 TIGRFAM 
                  5 . . . 772 
               
               
                 contig_1474 - ORF 1 
                 Cas9_a 
                 Pfam 
                 237 . . . 311 
               
               
                 contig_1474 - ORF 1 
                 Cas9_REC 
                 Pfam 
                 233 . . . 406 
               
               
                 contig_1474 - ORF 1 
                 HNH_4 
                 Pfam 
                 562 . . . 616 
               
               
                 contig_1474 - ORF 1 
                 HNH_CAS9 
                 PROSITE_PROFILES 
                 511 . . . 665 
               
               
                 contig_1474 - ORF 1 
                 RuvC_III 
                 Pfam 
                 659 . . . 751 
               
               
                 contig_1474 - ORF 1 
                 TIGR01865 
                 TIGRFAM 
                  3 . . . 768 
               
               
                 contig_226 - ORF 2 
                 Cas9-BH 
                 Pfam 
                 62 . . . 96 
               
               
                 contig_226 - ORF 2 
                 HNH_4 
                 Pfam 
                 829 . . . 879 
               
               
                 contig_226 - ORF 2 
                 HNH_CAS9 
                 PROSITE_PROFILES 
                 768 . . . 940 
               
               
                 contig_226 - ORF 2 
                 RuvC_III 
                 Pfam 
                  930 . . . 1136 
               
               
                 contig_433 - ORF 20 
                 HNH_4 
                 Pfam 
                 623 . . . 676 
               
               
                 contig_433 - ORF 20 
                 HNH_CAS9 
                 PROSITE_PROFILES 
                 564 . . . 727 
               
               
                 contig_433 - ORF 20 
                 RuvC_III 
                 Pfam 
                 719 . . . 811 
               
               
                 contig_433 - ORF 20 
                 TIGR01865 
                 TIGRFAM 
                 523 . . . 812 
               
               
                 contig_697 - ORF 2 
                 HNH_4 
                 Pfam 
                 574 . . . 636 
               
               
                 contig_697 - ORF 2 
                 HNH_CAS9 
                 PROSITE_PROFILES 
                 523 . . . 685 
               
               
                 contig_697 - ORF 2 
                 RuvC_III 
                 Pfam 
                 680 . . . 739 
               
               
                 contig_697 - ORF 2 
                 TIGR01865 
                 TIGRFAM 
                  5 . . . 772 
               
               
                 contig_1957 - ORF 1 
                 Cas9-BH 
                 Pfam 
                 62 . . . 93 
               
               
                 contig_1957 - ORF 1 
                 Cas9_PI 
                 Pfam 
                 1086 . . . 1331 
               
               
                 contig_1957 - ORF 1 
                 Cas9_REC 
                 Pfam 
                 181 . . . 724 
               
               
                 contig_1957 - ORF 1 
                 HNH_4 
                 Pfam 
                 832 . . . 882 
               
               
                 contig_1957 - ORF 1 
                 HNH_CAS9 
                 PROSITE_PROFILES 
                 781 . . . 932 
               
               
                 contig_1957 - ORF 1 
                 TIGR01865 
                 TIGRFAM 
                   4 . . . 1046 
               
               
                   
               
            
           
         
       
     
     Guide RNA Confirmation: To identify tracrRNA-coding regions, Hidden Markov Models (HMMs) of RNA structures and sequences are developed using previously published tracrRNAs (see, for example, Briner et al. (2014)  Molecular Cell  56:333-339, Briner and Barrangou (2016)  Cold Spring Harb Protoc ; doi: 10.1101/pdb.top090902, and U.S. Publication No. 2017/0275648, each of which is herein incorporated by reference in its entirety) as well as internal validated sequences. The HMM profile is used to predict the coding region for the tracrRNA. The corresponding crRNA is predicted by designing crRNAs that are partially complementary to the anti-repeat region of the tracrRNA, and to establish the functional modules seen in guide RNAs, including the lower stem, bulge, and upper stem. To verify that the newly identified RGN can bind the predicted crRNA, and in some embodiments, tracrRNA, a protein binding assay is performed. In one particular assay, RNAs labeled with a detectable label, such as biotin, are incubated with the RGN. The guide RNA is then pulled down with a binding partner of the detectable label (e.g., avidin) to pulldown bound RGN proteins. Confirmation of the binding can be visualized via SDS-PAGE or Western blot with antibodies that recognize the RGN protein or a detectable label bound to the RGN protein.