bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chromosome Break-Induced DNA Replication Leads to Nonreciprocal Translocations and Telomere Capture
Authors: Bosco Giovanni , Haber James E 
Published: April 2021

Abstract
In yeast, broken chromosomes can be repaired by recombination, resulting in nonreciprocal translocations. In haploid cells suffering an HO endonuclease-induced, double-strand break (DSB), nearly 2% of the broken chromosome ends recombined with a sequence near the opposite chromosome end, which shares only 72 bp of homology with the cut sequence. This produced a repaired chromosome with the same 20-kb sequence at each end. Diploid strains were constructed in which the broken chromosome shared homology with the unbroken chromosome only on the centromere-proximal side of the DSB. More than half of these cells repaired the DSB by copying sequences distal to the break from the unbroken template chromosome. All these events were RAD52 dependent. Pedigree analysis established that DSBs occurring in G1 were repaired by a replicative mechanism, producing two identical daughter cells. We discuss the implications of these data in understanding telomerase-independent replication of telomeres, gene amplification, and the evolution of chromosomal ends.
Mapping a Telomere Using the Translocation eT1(III;V) in Caenorhabditis elegans
Authors: Adames K A , Gawne Jocelyn , Wicky Chantal , Müller Fritz , Rose Ann M 
Published: April 2021

Abstract
In Caenorhabditis elegans, individuals heterozygous for a reciprocal translocation produce reduced numbers of viable progeny. The proposed explanation is that the segregational pattern generates aneuploid progeny. In this article, we have examined the genotype of arrested embryonic classes. Using appropriate primers in PCR amplifications, we identified one class of arrested embryo, which could be readily recognized by its distinctive spot phenotype. The corresponding aneuploid genotype was expected to be lacking the left portion of chromosome V, from the eT1 breakpoint to the left (unc-60) end. The phenotype of the homozygotes lacking this DNA was a stage 2 embryonic arrest with a dark spot coinciding with the location in wild-type embryos of birefringent gut granules. Unlike induced events, this deletion results from meiotic segregation patterns, eliminating complexity associated with unknown material that may have been added to the end of a broken chromosome. We have used the arrested embryos, lacking chromosome V left sequences, to map a telomere probe. Unique sequences adjacent to the telomeric repeats in the clone cTel3 were missing in the arrested spot embryo. The result was confirmed by examining aneuploid segregants from a second translocation, hT1(I;V). Thus, we concluded that the telomere represented by clone cTel3 maps to the left end of chromosome V. In this analysis, we have shown that reciprocal translocations can be used to generate segregational aneuploids. These aneuploids are deleted for terminal sequences at the noncrossover ends of the C. elegans autosomes.
DNA Variability and Recombination Rates at X-Linked Loci in Humans
Authors: Nachman Michael W , Bauer Vanessa L , Crowell Susan L , Aquadro Charles F 
Published: April 2021

Abstract
We sequenced 11,365 bp from introns of seven X-linked genes in 10 humans, one chimpanzee, and one orangutan to (i) provide an average estimate of nucleotide diversity (π) in humans, (ii) investigate whether there is variation in π among loci, (iii) compare ratios of polymorphism to divergence among loci, and (iv) provide a preliminary test of the hypothesis that heterozygosity is positively correlated with the local rate of recombination. The average value for π was low (0.063%, SE = 0.036%), about one order of magnitude smaller than for Drosophila melanogaster, the species for which the best data are available. Among loci, π varied by over one order of magnitude. Statistical tests of neutrality based on ratios of polymorphism to divergence or based on the frequency spectrum of variation within humans failed to reject a neutral, equilibrium model. However, there was a positive correlation between heterozygosity and rate of recombination, suggesting that the joint effects of selection and linkage are important in shaping patterns of nucleotide variation in humans.
Mitochondrial DNA Variation and Evolution of Japanese Black Cattle (Bos taurus)
Authors: Mannen H , Tsuji S , Loftus R T , Bradley D G 
Published: April 2021

Abstract
This article describes complete mitochondrial DNA displacement loop sequences from 32 Japanese Black cattle and the analysis of these data in conjunction with previously published sequences from African, European, and Indian subjects. The origins of North East Asian domesticated cattle are unclear. The earliest domestic cattle in the region were Bos taurus and may have been domesticated from local wild cattle (aurochsen; B. primigenius), or perhaps had an origin in migrants from the early domestic center of the Near East. In phylogenetic analyses, taurine sequences form a dense tree with a center consisting of intermingled European and Japanese sequences with one group of Japanese and another of all African sequences, each forming distinct clusters at extremes of the phylogeny. This topology and calibrated levels of sequence divergence suggest that the clusters may represent three different strains of ancestral aurochs, adopted at geographically and temporally separate stages of the domestication process. Unlike Africa, half of Japanese cattle sequences are topologically intermingled with the European variants. This suggests an interchange of variants that may be ancient, perhaps a legacy of the first introduction of domesticates to East Asia.
Genetics of Adaptive Radiation in Hawaiian and Cook Islands Species of Tetramolopium (Asteraceae). II. Genetic Linkage Map and Its Implications for Interspecific Breeding Barriers
Authors: Whitkus Richard 
Published: April 2021

Abstract
In a study of the genetic mechanisms associated with adaptive radiation in Hawaiian Tetramolopium, a genetic linkage map was constructed in an interspecific cross. A total of 125 RFLP and RAPD markers were mapped into 117 different loci on nine linkage groups for a map length of 665.7 cM. Segregation distortion occurred in 49% of the mapped probes, located primarily in four linkage groups. High percentages of one parental species genotype (Tetramolopium rockii) were recovered in three of these blocks and the second parental species (T. humile) in the remaining block. The high degree of distorted segregation suggests the buildup of internal crossing barriers, even though island plant species are typically characterized as highly cross compatible with few to no internal crossing barriers. This work and a review of previous crossing studies in island plants show that internal (postmating) crossing barriers do exist. The weak crossing barriers have likely been overlooked because the main focus has been on diversification and speciation through adaptation to extremely diverse environments.
Interchromosomal Recombination in Zea mays
Authors: Hu Weiming , Timmermans Marja C P , Messing Joachim 
Published: April 2021

Abstract
A new allele of the 27-kD zein locus in maize has been generated by interchromosomal recombination between chromosomes of two different inbred lines. A continuous patch of at least 11,817 bp of inbred W64A, containing the previously characterized Ra allele of the 27-kD zein gene, has been inserted into the genome of A188 by a single crossover. While both junction sequences are conserved, sequences of the two homologs between these junctions differ considerably. W64A contains the 7313-bp-long retrotransposon, Zeon-1. A188 contains a second copy of the 27-kD zein gene and a 2-kb repetitive element. Therefore, recombination results in a 7.3-kb insertion and a 14-kb deletion compared to the original S+A188 allele. If nonpairing sequences are looped out, 206 single base changes, frequently clustered, are present. The structure of this allele may explain how a recently discovered example of somatic recombination occurred in an A188/W64A hybrid. This would indicate that despite these sequence differences, pairing between these alleles could occur early during plant development. Therefore, such a somatically derived chimeric chromosome can also be heritable and give rise to new alleles.
Inference of Genome-Wide Mutation Rates and Distributions of Mutation Effects for Fitness Traits: A Simulation Study
Authors: Keightley Peter D 
Published: April 2021

Abstract
The properties and limitations of maximum likelihood (ML) inference of genome-wide mutation rates (U) and parameters of distributions of mutation effects are investigated. Mutation parameters are estimated from simulated experiments in which mutations randomly accumulate in inbred lines. ML produces more accurate estimates than the procedure of Bateman and Mukai and is more robust if the data do not conform to the model assumed. Unbiased ML estimates of the mutation effects distribution parameters can be obtained if a value for U can be assumed, but if U is estimated simultaneously with the distribution parameters, likelihood may increase monotonically as a function of U. If the distribution of mutation effects is leptokurtic, the number of mutation events per line is large, or if genotypic values are poorly estimated, only a lower limit for U, an upper limit for the mean mutation effect, and a lower limit for the kurtosis of the distribution can be given. It is argued that such lower (upper) limits are appropriate minima (maxima). Estimates of the mean mutational effect are unbiased but may convey little about the properties of the distribution if it is leptokurtic.
Constrained Disequilibrium Values and Hitchhiking in a Three-Locus System
Authors: Grote Mark N , Klitz William , Thomson Glenys 
Published: April 2021

Abstract
Positive selection on a new mutant allele can increase the frequencies of closely linked alleles (through hitchhiking), as well as create linkage disequilibrium between them. Because this disequilibrium is induced by the selected allele, one may be able to identify loci under selection by measuring the influence of a candidate locus on pairwise disequilibrium values at nearby loci. The constrained disequilibrium values (CDV) method approaches this problem by examining differences in pairwise disequilibrium values, which have been normalized for two- and three-locus systems, respectively. We have investigated in detail the reliability of inferences based on CDV, using simulation and analytical methods. Our main results are (i) in some circumstances, CDV may not distinguish well between a selected locus and a neighboring neutral locus, but (ii) CDV seldom indicates “selection” in neutral haplotypes with moderate to large 4Nc. We conclude that, although the CDV method does not appear to precisely locate selected alleles, it can be used to screen for regions in which hitchhiking is a plausible hypothesis. We present a microsatellite data set from human chromosome 6, in which constrained disequilibrium values suggest the action of selection in a region containing the human leukocyte antigen (HLA)-A and myelin oligodendrocyte glycoprotein (MOG) loci. The connection between hitchhiking and disequilibrium has received relatively little attention, so our investigation presents opportunities to address more general issues.
Sir3p Domains Involved in the Initiation of Telomeric Silencing in Saccharomyces cerevisiae
Authors: Park Yangsuk , Hanish John , Lustig Arthur J 
Published: April 2021

Abstract
Previous studies from our laboratory have demonstrated that tethering of Sir3p at the subtelomeric/telomeric junction restores silencing in strains containing Rap1-17p, a mutant protein unable to recruit Sir3p. This tethered silencing assay serves as a model system for the early events that follow recruitment of silencing factors, a process we term initiation. A series of LexA fusion proteins in-frame with various Sir3p fragments were constructed and tested for their ability to support tethered silencing. Interestingly, a region comprising only the C-terminal 144 amino acids, termed the C-terminal domain (CTD), is both necessary and sufficient for restoration of silencing. Curiously, the LexA-Sir3N205 mutant protein overcomes the requirement for the CTD, possibly by unmasking a cryptic initiation site. A second domain spanning amino acids 481-835, termed the nonessential for initiation domain (NID), is dispensable for the Sir3p function in initiation, but is required for the recruitment of the Sir4p C terminus. In addition, in the absence of the N-terminal 481 amino acids, the NID negatively influences CTD activity. This suggests the presence of a third region, consisting of the N-terminal half (1-481) of Sir3p, termed the positive regulatory domain (PRD), which is required to initiate silencing in the presence of the NID. These data suggest that the CTD “active” site is under both positive and negative control mediated by multiple Sir3p domains.
Sth1p, a Saccharomyces cerevisiae Snf2p/Swi2p Homolog, Is an Essential ATPase in RSC and Differs From Snf/Swi in Its Interactions With Histones and Chromatin-Associated Proteins
Authors: Du Jian , Nasir Irem , Benton Benjamin K , Kladde Michael P , Laurent Brehon C 
Published: April 2021

Abstract
The essential Sth1p is the protein most closely related to the conserved Snf2p/Swi2p in Saccharomyces cerevisiae. Sth1p purified from yeast has a DNA-stimulated ATPase activity required for its function in vivo. The finding that Sth1p is a component of a multiprotein complex capable of ATP-dependent remodeling of the structure of chromatin (RSC) in vitro, suggests that it provides RSC with ATP hydrolysis activity. Three sth1 temperature-sensitive mutations map to the highly conserved ATPase/helicase domain and have cell cycle and non-cell cycle phenotypes, suggesting multiple essential roles for Sth1p. The Sth1p bromodomain is required for wild-type function; deletion mutants lacking portions of this region are thermosensitive and arrest with highly elongated buds and 2C DNA content, indicating perturbation of a unique function. The pleiotropic growth defects of sth1-ts mutants imply a requirement for Sth1p in a general cellular process that affects several metabolic pathways. Significantly, an sth1-ts allele is synthetically sick or lethal with previously identified mutations in histones and chromatin assembly genes that suppress snf/swi, suggesting that RSC interacts differently with chromatin than Snf/Swi. These results provide a framework for understanding the ATP-dependent RSC function in modeling chromatin and its connection to the cell cycle.
The SFP1 Gene Product of Saccharomyces cerevisiae Regulates G2/M Transitions During the Mitotic Cell Cycle and DNA-Damage Response
Authors: Xu Zhiheng , Norris David 
Published: April 2021

Abstract
In eukaryotic cells, checkpoint pathways arrest cell-cycle progression if a particular event has failed to complete appropriately or if an important intracellular structure is defective or damaged. Saccharomyces cerevisiae strains that lack the SFP1 gene fail to arrest at the G2 DNA-damage checkpoint in response to genomic injury, but maintain their ability to arrest at the replication and spindle-assembly checkpoints. sfp1Δ mutants are characterized by a premature entrance into mitosis during a normal (undamaged) cell cycle, while strains that overexpress Sfp1p exhibit delays in G2. Sfp1p therefore acts as a repressor of the G2/M transition, both in the normal cell cycle and in the G2 checkpoint pathway. Sfp1 is a nuclear protein with two Cys2His2 zinc-finger domains commonly found in transcription factors. We propose that Sfp1p regulates the expression of gene products involved in the G2/M transition during the mitotic cell cycle and the DNA-damage response. In support of this model, overexpression of Sfp1p induces the expression of the PDS1 gene, which is known to encode a protein that regulates the G2 checkpoint.
Mutation in P0, a Dual Function Ribosomal Protein/Apurinic/Apyrimidinic Endonuclease, Modifies Gene Expression and Position Effect Variegation in Drosophila
Authors: Frolov Maxim V , Birchler James A 
Published: April 2021

Abstract
In a search for modifiers of gene expression with the white eye color gene as a target, a third chromosomal P-element insertion mutant l(3)01544 has been identified that exhibits a strong pigment increase in a white-apricot background. Molecular analysis shows that the P-element insertion is found in the first intron of the gene surrounding the insertion site. Sequencing both the cDNA and genomic fragments revealed that the identified gene is identical to one encoding ribosomal protein P0/apurinic/apyrimidinic endonuclease. The P-element-induced mutation, l(3)01544, affects the steady-state level of white transcripts and transcripts of some other genes. In addition, l(3)01544 suppresses the variegated phenotypes of In(1)wm4h and In(1)y3P, suggesting a potential involvement of the P0 protein in modifying position effect variegation. The revertant generated by the precise excision of the P element has lost all mutant phenotypes. Recent work revealed that Drosophila ribosomal protein P0 contains an apurinic/apyrimidinic endonuclease activity. Our results suggest that this multifunctional protein is also involved in regulation of gene expression in Drosophila.
A Genetic Screen of the Drosophila X Chromosome for Mutations That Modify Deformed Function
Authors: Florence Brian , McGinnis William 
Published: April 2021

Abstract
We have screened the Drosophila X chromosome for genes whose dosage affects the function of the homeotic gene Deformed. One of these genes, extradenticle, encodes a homeodomain transcription factor that heterodimerizes with Deformed and other homeotic Hox proteins. Mutations in the nejire gene, which encodes a transcriptional adaptor protein belonging to the CBP/p300 family, also interact with Deformed. The other previously characterized gene identified as a Deformed interactor is Notch, which encodes a transmembrane receptor. These three genes underscore the importance of transcriptional regulation and cell-cell signaling in Hox function. Four novel genes were also identified in the screen. One of these, rancor, is required for appropriate embryonic expression of Deformed and another homeotic gene, labial. Both Notch and nejire affect the function of another Hox gene, Ultrabithorax, indicating they may be required for homeotic activity in general.
DNA Polymorphism in Lycopersicon and Crossing-Over per Physical Length
Authors: Stephan Wolfgang , Langley Charles H 
Published: April 2021

Abstract
Surveys in Drosophila have consistently found reduced levels of DNA sequence polymorphism in genomic regions experiencing low crossing-over per physical length, while these same regions exhibit normal amounts of interspecific divergence. Here we show that for 36 loci across the genomes of eight Lycopersicon species, naturally occurring DNA polymorphism (scaled by locus-specific divergence between species) is positively correlated with the density of crossing-over per physical length. Large between-species differences in the amount of DNA sequence polymorphism reflect breeding systems: selfing species show much less within-species polymorphism than outcrossing species. The strongest association of expected heterozygosity with crossing-over is found in species with intermediate levels of average nucleotide diversity. All of these observations appear to be in qualitative agreement with the hitchhiking effects caused by the fixation of advantageous mutations and/or “background selection” against deleterious mutations.
The Rate of Spontaneous Mutation for Life-History Traits in Caenorhabditis elegans
Authors: Vassilieva Larissa L , Lynch Michael 
Published: April 2021

Abstract
Spontaneous mutations were accumulated in 100 replicate lines of Caenorhabditis elegans over a period of ∼50 generations. Periodic assays of these lines and comparison to a frozen control suggest that the deleterious mutation rate for typical life-history characters in this species is at least 0.05 per diploid genome per generation, with the average mutational effect on the order of 14% or less in the homozygous state and the average mutational heritability ∼0.0034. While the average mutation rate per character and the average mutational heritability for this species are somewhat lower than previous estimates for Drosophila, these differences can be reconciled to a large extent when the biological differences between these species are taken into consideration.
Complexity of Developmental Control: Analysis of Embryonic Cell Lineage Specification in Caenorhabditis elegans Using pes-1 as an Early Marker
Authors: Molin Laurent , Schnabel Heinke , Kaletta Titus , Feichtinger Richard , Hope Ian A , Schnabel Ralf 
Published: April 2021

Abstract
In the early Caenorhabditis elegans embryo five somatic founder cells are born during the first cleavages. The first of these founder cells, named AB, gives rise to 389 of the 558 nuclei present in the hatching larva. Very few genes directly involved in the specification of the AB lineage have been identified so far. Here we describe a screen of a large collection of maternal-effect embryonic lethal mutations for their effect on the early expression of a pes-1::lacZ fusion gene. This fusion gene is expressed in a characteristic pattern in 14 of the 32 AB descendants present shortly after the initiation of gastrulation. Of the 37 mutations in 36 genes suspected to be required specifically during development, 12 alter the expression of the pes-1::lacZ marker construct. The gene expression pattern alterations are of four types: reduction of expression, variable expression, ectopic expression in addition to the normal pattern, and reduction of the normal pattern together with ectopic expression. We estimate that ∼100 maternal functions are required to establish the pes-1 expression pattern in the early embryo.
Genetic Diversity of ospC in a Local Population of Borrelia burgdorferi sensu stricto
Authors: Wang Ing-Nang , Dykhuizen Daniel E , Qiu Weigang , Dunn John J , Bosler Edward M , Luft Benjamin J 
Published: April 2021

AbstractThe outer surface protein, OspC, is highly variable in Borrelia burgdorferi sensu stricto, the agent of Lyme disease. We have shown that even within a single population OspC is highly variable. The variation of ospA and ospC in the 40 infected deer ticks collected from a single site on Shelter Island, New York, was determined using PCR-SSCP. There is very strong apparent linkage disequilibrium between ospA and ospC alleles, even though they are located on separate plasmids. Thirteen discernible SSCP mobility classes for ospC were identified and the DNA sequence for each was determined. These sequences, combined with 40 GenBank sequences, allow us to define 19 major ospC groups. Sequences within a major ospC group are, on average, &lt;1% different from each other, while sequences between major ospC groups are, on average, ∼20% different. The tick sample contains 11 major ospC groups, GenBank contains 16 groups, with 8 groups found in both samples. Thus, the ospC variation within a local population is almost as great as the variation of a similar-sized sample of the entire species. The Ewens-Watterson-Slatkin test of allele frequency showed significant deviation from the neutral expectation, indicating balancing selection for these major ospC groups. The variation represented by major ospC groups needs to be considered if the OspC protein is to be used as a serodiagnostic antigen or a vaccine.