bluuebunny/crossref_metadata_2025_split huggingface dataset:
Hereditary lactate dehydrogenase A-subunit deficiency as cause of early postimplantation death of homozygotes in Mus musculus.
Authors: Merkle S , Favor J , Graw J , Hornhardt S , Pretsch W 
Published: January 2021

Abstract
Two ethylnitrosourea-induced heterozygous mouse mutants with approximately 58 and 50% of wild-type lactate dehydrogenase (LDH) activity and a gamma-ray-induced heterozygous mutant with 50% of wild-type LDH activity in blood, liver and spleen (expressing predominantly the Ldh-1 gene) were recovered in mutagenicity experiments following spermatogonial treatment. Physiological and genetic studies revealed no indications for differences in fertility as well as hematological or other physiological traits between heterozygotes of each mutant line and wild types. This suggests that neither the mutations in the heterozygous state per se nor the resulting approximate 42 to 50% LDH deficiency affect metabolism and fitness. Physicochemical and immunological studies clearly demonstrated that the two mutations with 50% deficiency in heterozygotes result from null alleles of the Ldh-1 structural locus, generating neither enzyme activity nor immunological cross-reacting material. In contrast, the heterozygous mutant with approximately 58% of normal blood LDH activity was shown to be due to a Ldh-1 allele creating protein subunits, which in random assortment with wild-type subunits in vivo exhibit a reduced specific activity and further alterations of kinetic and physicochemical characteristics. All the mutations in the homozygous state were found to be lethal at an early postimplantation stage of embryonic development, probably due to a block of glycolysis with the corresponding loss of the main source of metabolic energy during this ontogenetic stage. The distinct physiological consequences of the total absence of a functioning LDH-A subunit in mice and humans are discussed.(ABSTRACT TRUNCATED AT 250 WORDS)
A genetic map of the mouse suitable for typing intraspecific crosses.
Authors: Dietrich W , Katz H , Lincoln S E , Shin H S , Friedman J , Dracopoli N C , Lander E S 
Published: January 2021

Abstract
We report the construction of a genetic linkage map of the mouse, consisting entirely of genetic markers that can be rapidly typed by polymerase chain reaction and that show a high degree of polymorphism among inbred laboratory strains. Specifically, the map contains 317 simple sequence length polymorphisms at an average spacing of 4.3 cM and is detectably linked to approximately 99% of the mouse genome. In typical crosses between inbred laboratory strains, about 50% of the markers are polymorphic, making it straightforward to follow inheritance in almost any cross.
Ribosomal DNA is a site of chromosome breakage in aneuploid strains of Neurospora.
Authors: Butler D K 
Published: January 2021

Abstract
In wild-type strains of Neurospora crassa, the rDNA is located at a single site in the genome called the nucleolus organizer region (NOR), which forms a terminal segment on linkage group (LG) V. In the quasiterminal translocation strain T(I;V)AR190, most of the right arm of LG I moved to the distal tip of the NOR, and one or a few rDNA repeat units are moved to the truncated right arm of LG I. I report here that, in partial diploid strains derived from T(I;V)AR190, large terminal deletions result from chromosome breakage in the NOR. In most of these partial diploids, chromosome breakage is apparently frequent and the breakpoints occur in many parts of the NOR. The rDNA ends resulting from chromosome breakage are "healed" by the addition of new telomeres. Significantly, the presence of ectopic rDNA creates a new site of chromosome breakage in the genome of partial diploids. These results raise the possibility that, under certain conditions, rDNA is a region of fragility in eukaryotic chromosomes.
Use of a yeast site-specific recombinase to produce female germline chimeras in Drosophila.
Authors: Chou T B , Perrimon N 
Published: January 2021

Abstract
We describe an efficient method for generating female germline mosaics by inducing site-specific homologous mitotic recombination with a yeast recombinase (FLP) which is driven by a heat shock promoter. These germline mosaics are produced in flies heterozygous for the agametic, germline-dependent, dominant female sterile (DFS) mutation ovoD1, where only flies possessing germline clones are able to lay eggs. This method, the "FLP-DFS" technique, is very efficient because more than 90% of females with germline clones can be recovered. We show that this heat-inducible, site-specific mitotic recombination system does not affect viability and that the germline clones recovered are physiologically the same as those created by X-ray induced mitotic recombination. We describe the parameters of FLP-recombinase induced germline mitotic recombination and the use of the "FLP-DFS" technique to analyze the maternal effect of X-linked zygotic lethal mutations.
Inference of horizontal genetic transfer from molecular data: an approach using the bootstrap.
Authors: Lawrence J G , Hartl D L 
Published: January 2021

Abstract
Inconsistencies in taxonomic relationships implicit in different sets of nucleic acid sequences potentially result from horizontal transfer of genetic material between genomes. A nonparametric method is proposed to determine whether such inconsistencies are statistically significant. A similarity coefficient is calculated from ranked pairwise identities and evaluated against a distribution of similarity coefficients generated from resampled data. Subsequent analyses of partial data sets, obtained by the elimination of individual taxa, identify particular taxa to which the significance may be attributed, and can sometimes help in distinguishing horizontal genetic transfer from inconsistencies due to convergent evolution or variation in evolutionary rate. The method was successfully applied to data sets that were not found to be significantly different with existing methods that use comparisons of phylogenetic trees. The new statistical framework is also applicable to the inference of horizontal transfer from restriction fragment length polymorphism distributions and protein sequences.
Mutations in the second-largest subunit of Drosophila RNA polymerase II interact with Ubx.
Authors: Mortin M A , Zuerner R , Berger S , Hamilton B J 
Published: January 2021

Abstract
Specific mutations in the gene encoding the largest subunit of RNA polymerase II (RpII215) cause a partial transformation of a structure of the third thoracic segment, the capitellum, into the analogous structure of the second thoracic segment, the wing. This mutant phenotype is also caused by genetically reducing the cellular concentration of the transcription factor Ultrabithorax (Ubx). To recover mutations in the 140,000-D second-largest subunit of RNA polymerase II (RpII140) and determine whether any can cause a mutant phenotype similar to Ubx we attempted to identify all recessive-lethal mutable loci in a 340-kilobase deletion including this and other loci. One of the 13 complementation groups in this region encodes RpII140. Three RpII140 alleles cause a transformation of capitellum to wing but unlike RpII215 alleles, only when the concentration of Ubx protein is reduced by mutations in Ubx.
Reconstitutional mutagenesis of the maize P gene by short-range Ac transpositions.
Authors: Moreno M A , Chen J , Greenblatt I , Dellaporta S L 
Published: January 2021

Abstract
The tendency for Ac to transpose over short intervals has been utilized to develop insertional mutagenesis and fine structure genetic mapping strategies in maize. We recovered excisions of Ac from the P gene and insertions into nearby chromosomal sites. These closely linked Ac elements reinserted into the P gene, reconstituting over 250 unstable variegated alleles. Reconstituted alleles condition a variety of variegation patterns that reflect the position and orientation of Ac within the P gene. Molecular mapping and DNA sequence analyses have shown that reinsertion sites are dispersed throughout a 12.3-kb chromosomal region in the promoter, exons and introns of the P gene, but in some regions insertions sites were clustered in a nonrandom fashion. Transposition profiles and target site sequence data obtained from these studies have revealed several features of Ac transposition including its preference for certain target sites. These results clearly demonstrate the tendency of Ac to transpose to nearby sites in both proximal and distal directions from the donor site. With minor modifications, reconstitutional mutagenesis should be applicable to many Ac-induced mutations in maize and in other plant species and can possibly be extended to other eukaryotic transposon systems as well.
Testing for equality of evolutionary rates.
Authors: Muse S V , Weir B S 
Published: January 2021

Abstract
A likelihood ratio test is presented for comparing rates of evolutionary change in the paths of descent leading to two species. The test is compared to previous relative rate tests based on variances of estimated numbers of base substitutions. The likelihood approach allows for different transversion and transition rates, and when these rates are actually different, the likelihood ratio test can be much more powerful than the variance-based tests. For single-parameter mutation models, however, the two tests have similar power. The tests are applied to a set of chloroplast sequences from several species of grasses, and additional indications of significantly different rates leading to barley were found with the likelihood ratio test.
The yeast omnipotent suppressor SUP46 encodes a ribosomal protein which is a functional and structural homolog of the Escherichia coli S4 ram protein.
Authors: Vincent A , Liebman S W 
Published: January 2021

Abstract
The accurate synthesis of proteins is crucial to the existence of a cell. In yeast, several genes that affect the fidelity of translation have been identified (e.g., omnipotent suppressors, antisuppressors and allosuppressors). We have found that the dominant omnipotent suppressor SUP46 encodes the yeast ribosomal protein S13. S13 is encoded by two similar genes, but only the sup46 copy of the gene is able to fully complement the recessive phenotypes of SUP46 mutations. Both copies of the S13 genes contain introns. Unlike the introns of other duplicated ribosomal protein genes which are highly diverged, the duplicated S13 genes have two nearly identical DNA sequences of 25 and 31 bp in length within their introns. The SUP46 protein has significant homology to the S4 ribosomal protein in prokaryotic-type ribosomes. S4 is encoded by one of the ram (ribosomal ambiguity) genes in Escherichia coli which are the functional equivalent of omnipotent suppressors in yeast. Thus, SUP46 and S4 demonstrate functional as well as sequence conservation between prokaryotic and eukaryotic ribosomal proteins. SUP46 and S4 are most similar in their central amino acid sequences. Interestingly, the alterations resulting from the SUP46 mutations and the segment of the S4 protein involved in binding to the 16S rRNA are within this most conserved region.
Dominant effects of suppressor of Hairy-wing mutations on gypsy-induced alleles of forked and cut in Drosophila melanogaster.
Authors: Hoover K K , Gerasimova T I , Chien A J , Corces V G 
Published: January 2021

Abstract
Mutations induced by the gypsy retrotransposon in the forked (f) and cut (ct) loci render their expression under the control of the suppressor of Hairy-wing [su(Hw)] gene. This action is usually recessive, but su(Hw) acts as a dominant on the alleles fk, ctk and ctMRpN30. Molecular analysis of the gypsy element present in fk indicates that this allele is caused by the insertion of a modified gypsy in which the region normally containing twelve copies of the octamer-like repeat that interacts with the su(Hw) product is altered. Analysis of the gypsy element responsible for the ctk and ctMRpN30 mutations also reveals a correlation between the dominant action of su(Hw) and disruption of the octamer region. We propose that these disruptions alter the affinity and interaction of su(Hw) protein with gypsy DNA, thereby sensitizing the mutant phenotype to fluctuations in su(Hw) product.
The evolution of tandemly repetitive DNA: recombination rules.
Authors: Harding R M , Boyce A J , Clegg J B 
Published: January 2021

Abstract
Variable numbers of tandem repeats (VNTRs), which include hypervariable regions, minisatellites and microsatellites, can be assigned together with satellite DNAs to define a class of noncoding tandemly repetitive DNA (TR-DNA). The evolution of TR-DNA is assumed to be driven by an unbiased recombinational process. A simulation model of unequal exchange is presented and used to investigate the evolutionary persistence of single TR-DNA lineages. Three different recombination rules are specified to govern the expansion and contraction of a TR-DNA lineage from an initial array of two repeats to, finally, a single repeat allele, which cannot participate in a misalignment and exchange process. In the absence of amplification or selection acting to bias array evolution toward expansion, the probability of attaining a target array size is a function only of the initial number of repeats. We show that the proportions of lineages attaining a targeted array size are the same irrespective of recombination rule and rate, demonstrating that our simulation model is well behaved. The time taken to attain a target array size, the persistence of the target array, and the total persistence time of repetitive array structure, are functions of the initial number of repeats, the rate of recombination, and the rules of misalignment preceding recombinational exchange. These relationships are investigated using our simulation model. While misalignment constraint is probably greatest for satellite DNA it also seems important in accounting for the evolution of VNTR loci including minisatellites. This conclusion is consistent with the observed nonrandom distributions of VNTRs and other TR-DNAs in the human genome.
Population genetics of polymorphism and divergence.
Authors: Sawyer S A , Hartl D L 
Published: January 2021

Abstract
Frequencies of mutant sites are modeled as a Poisson random field in two species that share a sufficiently recent common ancestor. The selective effect of the new alleles can be favorable, neutral, or detrimental. The model is applied to the sample configurations of nucleotides in the alcohol dehydrogenase gene (Adh) in Drosophila simulans and Drosophila yakuba. Assuming a synonymous mutation rate of 1.5 x 10(-8) per site per year and 10 generations per year, we obtain estimates for the effective population size (N(e) = 6.5 x 10(6)), the species divergence time (tdiv = 3.74 million years), and an average selection coefficient (sigma = 1.53 x 10(-6) per generation for advantageous or mildly detrimental replacements), although it is conceivable that only two of the amino acid replacements were selected and the rest neutral. The analysis, which includes a sampling theory for the independent infinite sites model with selection, also suggests the estimate that the number of amino acids in the enzyme that are susceptible to favorable mutation is in the range 2-23 at any one time. The approach provides a theoretical basis for the use of a 2 x 2 contingency table to compare fixed differences and polymorphic sites with silent sites and amino acid replacements.
Tn7 transposition creates a hotspot for homologous recombination at the transposon donor site.
Authors: Hagemann A T , Craig N L 
Published: January 2021

Abstract
Homologous recombination at the bacterial transposon Tn7 donor site is stimulated 10-fold when Tn7 is activated to transpose at high frequency in RecD- Escherichia coli, where recombination is focused near the ends of double-chain breaks. This is observed as an increase in recombination between two lacZ heteroalleles when one copy of lacZ carries within it a Tn7 that is transposing at high frequency. This stimulation of recombination is dependent upon the presence of homology with the donor site, is independent of SOS induction, and is not due to a global stimulation of recombination. When stimulated by Tn7 transposition, the conversion events giving rise to Lac+ recombinants occur preferentially at the site of Tn7, suggesting that transposition is stimulating gene conversion at the donor site. These results support the model that Tn7 transposition occurs by a "cut and paste" mechanism, leaving a double-chain break at the donor site that is repaired by the host homologous recombination machinery; normally, repair would use homology in a sister chromosome to regenerate a copy of the transposon. This proposed series of events allows transposition that is nonreplicative, per se, to be effectively replicative.
A short chromosomal region with major roles in yeast chromosome III meiotic disjunction, recombination and double strand breaks.
Authors: Goldway M , Sherman A , Zenvirth D , Arbel T , Simchen G 
Published: January 2021

Abstract
A multicopy plasmid was isolated from a yeast genomic library, whose presence resulted in a twofold increase in meiotic nondisjunction of chromosome III. The plasmid contains a 7.5-kb insert from the middle of the right arm of chromosome III, including the gene THR4. Using chromosomal fragments derived from chromosome III, we determined that the cloned region caused a significant, specific, cis-acting increase in chromosome III nondisjunction in the first meiotic division. The plasmid containing this segment exhibited high spontaneous meiotic integration into chromosome III (in 2.4% of the normal meiotic divisions) and a sixfold increase (15.5%) in integration in nondisjunctant meioses. Genetic analysis of the cloned region revealed that it contains a "hot spot" for meiotic recombination. In DNA of rad50S mutant cells, a strong meiosis-induced double strand break (DSB) signal was detected in this region. We discuss the possible relationships between meiosis-induced DSBs, recombination and chromosome disjunction, and propose that recombinational hot spots may be "pairing sites" for homologous chromosomes in meiosis.
Telomere-mediated plasmid segregation in Saccharomyces cerevisiae involves gene products required for transcriptional repression at silencers and telomeres.
Authors: Longtine M S , Enomoto S , Finstad S L , Berman J 
Published: January 2021

Abstract
Plasmids that contain Saccharomyces cerevisiae TG1-3 telomere repeat sequences (TRS plasmids) segregate efficiently during mitosis. Mutations in histone H4 reduce the efficiency of TRS-mediated plasmid segregation, suggesting that chromatin structure is involved in this process. Sir2, Sir3 and Sir4 are required for the transcriptional repression of genes located at the silent mating type loci (HML and HMR) and at telomeres (telomere position effect) and are also involved in the segregation of TRS plasmids, indicating that TRS-mediated plasmid segregation involves factors that act at chromosomal telomeres. TRS plasmid segregation differes from the segregation of plasmids carrying the HMR E silencing region: HMR E plasmid segregation function is completely dependent upon Sir2, Sir3 and Sir4, involves Sir1 and is not influenced by mutations in RAP 1 that eliminate TRS plasmid segregation. Mutations in SIR1, SIN1, TOP1, TEL1 and TEL2 do not influence TRS plasmid segregation. Unlike transcriptional repression at telomeres, TRS plasmids retain partial segregation function in sir2, sir3, sir4, nat1 and ard1 mutant strains. Thus it is likely that TRS plasmid segregation involves additional factors that are not involved in telomere position effect.
A ubiquitin-conjugating enzyme, RAD6, affects the distribution of Ty1 retrotransposon integration positions.
Authors: Liebman S W , Newnam G 
Published: January 2021

Abstract
A galactose-inducible Ty1 element was used to generate 59 independent Ty1 inserts that inactivate the CAN1 gene. As found in previous studies, the distribution of these elements shows a gradient of insertion frequency from highest to lowest between the 5' and 3' ends of the gene. However, 53 independent Ty1 and Ty2 insertions isolated by an identical procedure in an isogenic rad6 deletion strain do not show this bias. In this strain, the Ty elements insert randomly throughout CAN1. These results show that the ubiquitin-conjugating enzyme, RAD6, alters the integration site preferences of Ty1 retrotransposons.
Molecular and genetic analysis of unc-7, a Caenorhabditis elegans gene required for coordinated locomotion.
Authors: Starich T A , Herman R K , Shaw J E 
Published: January 2021

Abstract
Mutations in the Caenorhabditis elegans gene unc-7 confer an uncoordinated phenotype. Wild-type animals trace smooth, sinuous waves as they move; unc-7 mutants make irregular bends or kinks along their bodies, particularly when they move forward. The unc-7 locus has also been implicated in the nematode's response to volatile anesthetics. We have cloned unc-7 by transposon tagging: an unc-7 mutation was correlated with the insertion of the transposon Tc1, and reversion of the mutant phenotype was correlated with loss of the Tc1 element. We have physically mapped the region flanking the sites of Tc1 insertion and identified DNA rearrangements corresponding to eight additional unc-7 alleles. Northern analysis indicates that a 2.7-kb unc-7 message is present in all developmental stages but is most abundant in L1-L3 larvae. The 5' end of the message contains a trans-spliced leader SL1. An 18-kb intron is located upstream of the predicted translational start site of the gene, and DNA breakpoints of four gamma-ray-induced alleles were located within this intron. We determined the sequence of a cDNA corresponding to the unc-7 message. The message may encode a 60-kd protein whose amino acid sequence is unrelated to any other available protein sequence; a transmembrane location for the unc-7 protein is predicted. We predict from our analysis of unc-7 genetic mosaics that the unc-7 gene product is not required in muscle cells for wild-type coordination but is probably required in motor neurons (although a hypodermal role has not been excluded). We speculate that unc-7 may be involved in the function of neuronal ion channels.
Isolation of mutations affecting neural circuitry required for grooming behavior in Drosophila melanogaster.
Authors: Phillis R W , Bramlage A T , Wotus C , Whittaker A , Gramates L S , Seppala D , Farahanchi F , Caruccio P , Murphey R K 
Published: January 2021

Abstract
We have developed a screen for the isolation of mutations that produce neural defects in adult Drosophila melanogaster. In this screen, we identify mutants as flies unable to remove a light coating of applied dust in a 2-hr period. We have recovered and characterized six mutations and have found that they produce coordination defects and some have reduced levels of reflex responsiveness to the stimulation of single tactile sensory bristles. The grooming defects produced by all six of the mutations are recessive, and each of the mutations has been genetically mapped. We have also used our assay to test the grooming ability of stocks containing mutations that produce known neural defects.