bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Matrix Coalescent and an Application to Human Single-Nucleotide Polymorphisms
Authors: Wooding Stephen , Rogers Alan 
Published: April 2021

AbstractThe “matrix coalescent” is a reformulation of the familiar coalescent process of population genetics. It ignores the topology of the gene tree and treats the coalescent as a Markov process describing the decay in the number of ancestors of a sample of genes as one proceeds backward in time. The matrix formulation of this process is convenient when the population changes in size, because such changes affect only the eigenvalues of the transition matrix, not the eigenvectors. The model is used here to calculate the expectation of the site frequency spectrum under various assumptions about population history. To illustrate how this method can be used with data, we then use it in conjunction with a set of SNPs to test hypotheses about the history of human population size.
Testing Models of Selection and Demography in Drosophila simulans
Authors: Wall Jeffrey D , Andolfatto Peter , Przeworski Molly 
Published: April 2021

Abstract
We analyze patterns of nucleotide variability at 15 X-linked loci and 14 autosomal loci from a North American population of Drosophila simulans. We show that there is significantly more linkage disequilibrium on the X chromosome than on chromosome arm 3R and much more linkage disequilibrium on both chromosomes than expected from estimates of recombination rates, mutation rates, and levels of diversity. To explore what types of evolutionary models might explain this observation, we examine a model of recurrent, nonoverlapping selective sweeps and a model of a recent drastic bottleneck (e.g., founder event) in the demographic history of North American populations of D. simulans. The simple sweep model is not consistent with the observed patterns of linkage disequilibrium nor with the observed frequencies of segregating mutations. Under a restricted range of parameter values, a simple bottleneck model is consistent with multiple facets of the data. While our results do not exclude some influence of selection on X vs. autosome variability levels, they suggest that demography alone may account for patterns of linkage disequilibrium and the frequency spectrum of segregating mutations in this population of D. simulans.
An Allelic Series of Mutations in theKit ligandGene of Mice. II. Effects of Ethylnitrosourea-InducedKitlPoint Mutations on Survival and Peripheral Blood Cells ofKitlSteelMice
Authors: Rajaraman S , Davis W S , Mahakali-Zama A , Evans H K , Russell L B , Bedell M A 
Published: April 2021

AbstractThe ligand for the Kit receptor tyrosine kinase is Kit ligand (Kitl; also known as mast cell growth factor, stem cell factor, and Steel factor), which is encoded at the Steel (Sl) locus of mice. Previous studies revealed that KitlSl mutations have semidominant effects; mild pigmentation defects and macrocytic, hypoplastic anemia occur in heterozygous mice, and more severe pigmentation defects and anemia occur in homozygotes. Lethality also occurs in mice homozygous for severe KitlSl mutations. We describe the effects of seven new N-ethyl-N-nitrosourea (ENU)-induced KitlSl mutations and two previously characterized severe KitlSl mutations on pigmentation, peripheral blood cells, and mouse survival. Mice heterozygous for each of the nine mutations had reduced coat pigmentation and macrocytosis of peripheral blood. In the case of some of these mutations, however, red blood cell (RBC) counts, hemoglobin concentrations, and hematocrits were normal in heterozygotes, even though homozygotes exhibited severely reduced RBC counts and lethality. In homozygous mice, the extent of anemia generally correlates with effects on viability for most KitlSl mutations; i.e., most mutations that cause lethality also cause a more severe anemia than that of mutations that allow viability. Interestingly, lethality and anemia were not directly correlated in the case of one KitlSl mutation.
Measures of Synteny Conservation Between Species Pairs
Authors: Housworth Elizabeth Ann , Postlethwait John 
Published: April 2021

Abstract
Measures of conserved synteny are important for estimating the relative rates of chromosomal evolution in various lineages. We present a natural way to view the synteny conservation between two species from an Oxford grid—an r × c table summarizing the number of orthologous genes on each of the chromosomes 1 through r of the first species that are on each of the chromosomes 1 through c of the second species. This viewpoint suggests a natural statistic, which we denote by ρ and call syntenic correlation, designed to measure the amount of synteny conservation between two species. This measure allows syntenic conservation to be compared across many pairs of species. We improve the previous methods for estimating the true number of conserved syntenies given the observed number of conserved syntenies by taking into account the dependency of the numbers of orthologues observed in the chromosome pairings between the two species and by determining both point and interval estimators. We also discuss the application of our methods to genomes that contain chromosomes of highly variable lengths and to estimators of the true number of conserved segments between species pairs.
Identification ofvib-1, a Locus Involved in Vegetative Incompatibility Mediated byhet-cinNeurospora crassa
Authors: Xiang Qijun , Glass N Louise 
Published: April 2021

AbstractA non-self-recognition system called vegetative incompatibility is ubiquitous in filamentous fungi and is genetically regulated by het loci. Different fungal individuals are unable to form viable heterokaryons if they differ in allelic specificity at a het locus. To identify components of vegetative incompatibility mediated by allelic differences at the het-c locus of Neurospora crassa, we isolated mutants that suppressed phenotypic aspects of het-c vegetative incompatibility. Three deletion mutants were identified; the deletions overlapped each other in an ORF named vib-1 (vegetative incompatibility blocked). Mutations in vib-1 fully relieved growth inhibition and repression of conidiation conferred by het-c vegetative incompatibility and significantly reduced hyphal compartmentation and death rates. The vib-1 mutants displayed a profuse conidiation pattern, suggesting that VIB-1 is a regulator of conidiation. VIB-1 shares a region of similarity to PHOG, a possible phosphate nonrepressible acid phosphatase in Aspergillus nidulans. Native gel analysis of wild-type strains and vib-1 mutants indicated that vib-1 is not the structural gene for nonrepressible acid phosphatase, but rather may regulate nonrepressible acid phosphatase activity.
Fitness Evolution and the Rise of Mutator Alleles in Experimental Escherichia coli Populations
Authors: Shaver Aaron C , Dombrowski Peter G , Sweeney Joseph Y , Treis Tania , Zappala Renata M , Sniegowski Paul D 
Published: April 2021

Abstract
We studied the evolution of high mutation rates and the evolution of fitness in three experimental populations of Escherichia coli adapting to a glucose-limited environment. We identified the mutations responsible for the high mutation rates and show that their rate of substitution in all three populations was too rapid to be accounted for simply by genetic drift. In two of the populations, large gains in fitness relative to the ancestor occurred as the mutator alleles rose to fixation, strongly supporting the conclusion that mutator alleles fixed by hitchhiking with beneficial mutations at other loci. In one population, no significant gain in fitness relative to the ancestor occurred in the population as a whole while the mutator allele rose to fixation, but a substantial and significant gain in fitness occurred in the mutator subpopulation as the mutator neared fixation. The spread of the mutator allele from rarity to fixation took &gt;1000 generations in each population. We show that simultaneous adaptive gains in both the mutator and wild-type subpopulations (clonal interference) retarded the mutator fixation in at least one of the populations. We found little evidence that the evolution of high mutation rates accelerated adaptation in these populations.
A Genomics-Based Screen for Yeast Mutants With an Altered Recombination/End-Joining Repair Ratio
Authors: Wilson Thomas E 
Published: April 2021

Abstract
We recently described a yeast assay suitable for genetic screening in which simple religation nonhomologous end-joining (NHEJ) and single-strand annealing (SSA) compete for repair of an I-SceI-created double-strand break. Here, the required allele has been introduced into an array of 4781 MATa deletion mutants and each strain screened individually. Two mutants (rad52 and srs2) showed a clear increase in the NHEJ/SSA ratio due to preferential impairment of SSA, but no mutant increased the absolute frequency of NHEJ significantly above the wild-type level. Seven mutants showed a decreased NHEJ/SSA ratio due to frank loss of NHEJ, which corresponded to all known structural/catalytic NHEJ components (yku70, yku80, dnl4, lif1, rad50, mre11, and xrs2); no new mutants in this category were identified. A clearly separable and surprisingly large set of 16 other mutants showed partial defects in NHEJ. Further examination of these revealed that NEJ1 can entirely account for the mating-type regulation of NHEJ, but that this regulatory role was distinct from the postdiauxic/stationary-phase induction of NHEJ that was deficient in other mutants (especially doa1, fyv6, and mck1). These results are discussed in the context of the minimal set of required proteins and regulatory inputs for NHEJ.
Exploring the Envelope: Systematic Alteration in the Sex-Determination System of the Nematode Caenorhabditis elegans
Authors: Hodgkin Jonathan 
Published: April 2021

Abstract
The natural sexes of the nematode Caenorhabditis elegans are the self-fertilizing hermaphrodite (XX) and the male (XO). The underlying genetic pathway controlling sexual phenotype has been extensively investigated. Mutations in key regulatory genes have been used to create a series of stable populations in which sex is determined not by X chromosome dosage, but in a variety of other ways, many of which mimic the diverse sex-determination systems found in different animal species. Most of these artificial strains have male and female sexes. Each of seven autosomal genes can be made to adopt a role as the primary determinant of sex, and each of the five autosomes can carry the primary determinant, thereby becoming a sex chromosome. Strains with sex determination by fragment chromosomes, episomes, compound chromosomes, or environmental factors have also been constructed. The creation of these strains demonstrates the ease with which one sex-determination system can be transformed into another.
A Mutation in the Promoter of Desaturase 2 Is Correlated With Sexual Isolation Between Drosophila Behavioral Races
Authors: Fang Shu , Takahashi Aya , Wu Chung-I 
Published: April 2021

Abstract
Examples of genes governing behavioral isolation are scarce. Here we report that a regulatory mutation in desaturase 2, known to determine a pheromonal polymorphism in Drosophila melanogaster females, may be such an example. This mutation is strongly correlated with the mating pattern between the Zimbabwe and cosmopolitan races of this species. These two behavioral races appear to be at the incipient stage of speciation. The desaturase 2 mutation may be one of the many loci underlying the behavioral differences between the two races.
Rates of R1 and R2 Retrotransposition and Elimination From the rDNA Locus of Drosophila melanogaster
Authors: Pérez-González César E , Eickbush Thomas H 
Published: April 2021

Abstract
R1 and R2 elements are non-LTR retrotransposons that insert specifically into the 28S rRNA genes of arthropods. The process of concerted evolution of the rDNA locus should give rise to rapid turnover of these mobile elements compared to elements that insert at sites throughout a genome. To estimate the rate of R1 and R2 turnover we have examined the insertion of new elements and elimination of old elements in the Harwich mutation accumulation lines of Drosophila melanogaster, a set of inbred lines maintained for &gt;350 generations. Nearly 300 new insertion and elimination events were observed in the 19 Harwich lines. The retrotransposition rate for R1 was 18 times higher than the retrotransposition rate for R2. Both rates were within the range previously found for retrotransposons that insert outside the rDNA loci in D. melanogaster. The elimination rates of R1 and R2 from the rDNA locus were similar to each other but over two orders of magnitude higher than that found for other retrotransposons. The high rates of R1 and R2 elimination from the rDNA locus confirm that these elements must maintain relatively high rates of retrotransposition to ensure their continued presence in this locus.
Estimation of Quantitative Trait Locus Allele Frequency via a Modified Granddaughter Design
Authors: Weller Joel Ira , Weller Hayim , Kliger David , Ron Micha 
Published: April 2021

Abstract
A method is described on the basis of a modification of the granddaughter design to obtain estimates of quantitative trait loci (QTL) allele frequencies in dairy cattle populations and to determine QTL genotypes for both homozygous and heterozygous grandsires. The method is based on determining the QTL allele passed from grandsires to their maternal granddaughters using haplotypes consisting of several closely linked genetic markers. This method was applied to simulated data of 10 grandsire families, each with 500 granddaughters, and a QTL with a substitution effect of 0.4 phenotypic standard deviations and to actual data for a previously analyzed QTL in the center of chromosome 6, with substitution effect of 1 phenotypic standard deviation on protein percentage. In the simulated data the standard error for the estimated QTL substitution effect with four closely linked multiallelic markers was only 7% greater than the expected standard error with completely correct identification of QTL allele origin. The method estimated the population QTL allelic frequency as 0.64 ± 0.07, compared to the simulated value of 0.7. In the actual data, the frequency of the allele that increases protein percentage was estimated as 0.63 ± 0.06. In both data sets the hypothesis of equal allelic frequencies was rejected at P &lt; 0.05.
Genetic Analysis of Natural Variations in the Architecture ofArabidopsis thalianaVegetative Leaves
Authors: Pérez-Pérez José Manuel , Serrano-Cartagena José , Micol José Luis 
Published: April 2021

AbstractTo ascertain whether intraspecific variability might be a source of information as regards the genetic controls underlying plant leaf morphogenesis, we analyzed variations in the architecture of vegetative leaves in a large sample of Arabidopsis thaliana natural races. A total of 188 accessions from the Arabidopsis Information Service collection were grown and qualitatively classified into 14 phenotypic classes, which were defined according to petiole length, marginal configuration, and overall lamina shape. Accessions displaying extreme and opposite variations in the above-mentioned leaf architectural traits were crossed and their F2 progeny was found to be not classifiable into discrete phenotypic classes. Furthermore, the leaf trait-based classification was not correlated with estimates on the genetic distances between the accessions being crossed, calculated after determining variations in repeat number at 22 microsatellite loci. Since these results suggested that intraspecific variability in A. thaliana leaf morphology arises from an accumulation of mutations at quantitative trait loci (QTL), we studied a mapping population of recombinant inbred lines (RILs) derived from a Landsberg erecta-0 × Columbia-4 cross. A total of 100 RILs were grown and the third and seventh leaves of 15 individuals from each RIL were collected and morphometrically analyzed. We identified a total of 16 and 13 QTL harboring naturally occurring alleles that contribute to natural variations in the architecture of juvenile and adult leaves, respectively. Our QTL mapping results confirmed the multifactorial nature of the observed natural variations in leaf architecture.
Enrichment and Elimination of mutY Mutators in Escherichia coli Populations
Authors: Notley-McRobb Lucinda , Seeto Shona , Ferenci Thomas 
Published: April 2021

Abstract
The kinetics of mutator sweeps was followed in two independent populations of Escherichia coli grown for up to 350 generations in glucose-limited continuous culture. A rapid elevation of mutation rates was observed in both populations within 120-150 generations, as was apparent from major increases in the proportion of the populations with unselected mutations in fhuA. The increase in mutation rates was due to sweeps by mutY mutators. In both cultures, the enrichment of mutators resulted from hitchhiking with identified beneficial mutations increasing fitness under glucose limitation; mutY hitchhiked with mgl mutations in one culture and ptsG in the other. In both cases, mutators were enriched to constitute close to 100% of the population before a periodic selection event reduced the frequency of unselected mutations and mutators in the cultures. The high proportion of mutators persisted for 150 generations in one population but began to be eliminated within 50 generations in the other. The persistence of mutator, as well as experimental data showing that mutY bacteria were as fit as near-isogenic mutY+ bacteria in competition experiments, suggest that mutator load by deleterious mutations did not explain the rapidly diminishing proportion of mutators in the populations. The nonmutators sweeping out mutators were also unlikely to have arisen by reversion or antimutator mutations; the mutY mutations were major deletions in each case and the bacteria sweeping out mutators contained intact mutY. By following mgl allele frequencies in one population, we discovered that mutators were outcompeted by bacteria that had rare mgl mutations previously as well as additional beneficial mutation(s). The pattern of appearance of mutY, but not its elimination, conforms to current models of mutator sweeps in bacterial populations. A mutator with a narrow mutational spectrum like mutY may be lost if the requirement for beneficial mutations is for changes other than GC → TA transversions. Alternatively, epistatic interactions between mutator mutation and beneficial mutations need to be postulated to explain mutator elimination.
High-Resolution Genetic Mapping With Ordered Arrays of Saccharomyces cerevisiae Deletion Mutants
Authors: Jorgensen Paul , Nelson Bryce , Robinson Mark D , Chen Yiqun , Andrews Brenda , Tyers Mike , Boone Charles 
Published: April 2021

Abstract
We present a method for high-resolution genetic mapping that takes advantage of the ordered set of viable gene deletion mutants, which form a set of colinear markers covering almost every centimorgan of the Saccharomyces cerevisiae genome, and of the synthetic genetic array (SGA) system, which automates the construction of double mutants formed by mating and meiotic recombination. The Cbk1 kinase signaling pathway, which consists minimally of CBK1, MOB2, KIC1, HYM1, and TAO3 (PAG1), controls polarized morphogenesis and activation of the Ace2 transcription factor. Deletion mutations in the Cbk1 pathway genes are tolerated differently by common laboratory strains of S. cerevisiae, being viable in the W303 background but dead in the S288C background. Genetic analysis indicated that the lethality of Cbk1 pathway deletions in the S288C background was suppressed by a single allele specific to the W303 background. SGA mapping (SGAM) was used to locate this W303-specific suppressor to the SSD1 locus, which contains a known polymorphism that appears to compromise SSD1 function. This procedure should map any mutation, dominant or recessive, whose phenotype is epistatic to wild type, that is, a phenotype that can be scored from a mixed population of cells obtained by germination of both mutant and wild-type spores. In principle, SGAM should be applicable to the analysis of multigenic traits. Large-scale construction of ordered mutations in other model organisms would broaden the application of this approach.
Regulation of I-Transposon Activity in Drosophila: Evidence for Cosuppression of Nonhomologous Transgenes and Possible Role of Ancestral I-Related Pericentromeric Elements
Authors: Jensen Silke , Gassama Marie-Pierre , Dramard Xavier , Heidmann Thierry 
Published: April 2021

Abstract
We have previously shown that the activity of functional I retrotransposons (I factors) introduced into Drosophila devoid of such elements can be repressed by transgenes containing an internal fragment of the I factor itself and that this repressing effect presents the characteristic features of homology-dependent gene silencing or cosuppression. Here we show that the same transgenes can induce silencing of a nonhomologous reporter gene containing as the sole I-factor sequence its 100-bp promoter fragment. Silencing of the nonhomologous reporter gene shows strong similarities to I-factor cosuppression: It does not require any translation product from the regulating transgenes, sense and antisense constructs are equally potent, and the silencing effect is only maternally transmitted and fully reversible. A search for genomic I-like sequences containing domains with similarities to those of both the regulating and the reporter transgenes led to the identification of four such elements, which therefore could act as intermediates—or relays—in the cosuppression machinery. These results strongly suggest that ancestral transposition-defective I-related elements, which are naturally present in the Drosophila genome, may participate per se in the natural conditions of I-factor silencing.
Enhancer of terminal gene conversion, a New Mutation in Drosophila melanogaster That Induces Telomere Elongation by Gene Conversion
Authors: Melnikova Larisa , Georgiev Pavel 
Published: April 2021

Abstract
Telomeres of Drosophila melanogaster contain arrays of the retrotransposon-like elements HeT-A and TART. Terminally deleted chromosomes can be maintained for many generations. Thus, broken chromosome ends behave as real telomeres. It was previously shown that gene conversion may extend the broken ends. Here we found that the frequency of terminal DNA elongation by gene conversion strongly depends on the genotype. A dominant E(tc) (Enhancer of terminal gene conversion) mutation markedly increases the frequency of this event but does not significantly influence the frequency of HeT-A and TART attachment to the broken chromosome end and recombination between directly repeated sequences at the end of the truncated chromosome. The E(tc) mutation was mapped to the 91-93 region on chromosome 3. Drosophila lines that bear the E(tc) mutation for many generations have telomeres, consisting of HeT-A and TART elements, that are longer than those found in wild-type lines. Thus, the E(tc) mutation plays a significant role in the control of telomere elongation in D. melanogaster.