bluuebunny/crossref_metadata_2025_split huggingface dataset:
Unraveling selection in the mitochondrial genome of Drosophila.
Authors: Ballard J W , Kreitman M 
Published: January 2021

Abstract
We examine mitochondrial DNA variation at the cytochrome b locus within and between three species of Drosophila to determine whether patterns of variation conform to the predictions of neutral molecular evolution. The entire 1137-bp cytochrome b locus was sequenced in 16 lines of Drosophila melanogaster, 18 lines of Drosophila simulans and 13 lines of Drosophila yakuba. Patterns of variation depart from neutrality by several test criteria. Analysis of the evolutionary clock hypothesis shows unequal rates of change along D. simulans lineages. A comparison within and between species of the ratio of amino acid replacement change to synonymous change reveals a relative excess of amino acid replacement polymorphism compared to the neutral prediction, suggestive of slightly deleterious or diversifying selection. There is evidence for excess homozygosity in our world wide sample of D. melanogaster and D. simulans alleles, as well as a reduction in the number of segregating sites in D. simulans, indicative of selective sweeps. Furthermore, a test of neutrality for codon usage shows the direction of mutations at third positions differs among different topological regions of the gene tree. The analyses indicate that molecular variation and evolution of mtDNA are governed by many of the same selective forces that have been shown to govern nuclear genome evolution and suggest caution be taken in the use of mtDNA as a "neutral" molecular marker.
Substitution processes in molecular evolution. III. Deleterious alleles.
Authors: Gillespie J H 
Published: January 2021

Abstract
The substitution processes for various models of deleterious alleles are examined using computer simulations and mathematical analyses. Most of the work focuses on the house-of-cards model, which is a popular model of deleterious allele evolution. The rate of substitution is shown to be a concave function of the strength of selection as measured by alpha = 2N sigma, where N is the population size and sigma is the standard deviation of fitness. For alpha &lt; 1, the house-of-cards model is essentially a neutral model; for alpha &gt; 4, the model ceases to evolve. The stagnation for large alpha may be understood by appealing to the theory of records. The house-of-cards model evolves to a state where the vast majority of all mutations are deleterious, but precisely one-half of those mutations that fix are deleterious (the other half are advantageous). Thus, the model is not a model of exclusively deleterious evolution as is frequently claimed. It is argued that there are no biologically reasonable models of molecular evolution where the vast majority of all substitutions are deleterious. Other models examined include the exponential and gamma shift models, the Hartl-Dykhuizen-Dean (HDD) model, and the optimum model. Of all those examined, only the optimum and HDD models appear to be reasonable candidates for silent evolution. None of the models are viewed as good candidates for protein evolution, as none are both biologically reasonable and exhibit the variability in substitutions commonly observed in protein sequence data.
sine oculis is a homeobox gene required for Drosophila visual system development.
Authors: Serikaku M A , O'Tousa J E 
Published: January 2021

Abstract
The somda (sine oculis-medusa) mutant is the result of a P element insertion at position 43C on the second chromosome. somda causes aberrant development of the larval photoreceptor (Bolwig's) organ and the optic lobe primordium in the embryo. Later in development, adult photoreceptors fail to project axons into the optic ganglion. Consequently optic lobe development is aborted and photoreceptor cells show age-dependent retinal degeneration. The so gene was isolated and characterized. The gene encodes a homeodomain protein expressed in the optic lobe primordium and Bolwig's organ of embryos, in the developing adult visual system of larvae, and in photoreceptor cells and optic lobes of adults. In addition, the SO product is found at invagination sites during embryonic development: at the stomadeal invagination, the cephalic furrow, and at segmental boundaries. The mutant somda allele causes severe reduction of SO embryonic expression but maintains adult visual system expression. Ubiquitous expression of the SO gene product in 4-8-hr embryos rescues all somda mutant abnormalities, including the adult phenotypes. Thus, all deficits in adult visual system development and function results from failure to properly express the so gene during embryonic development. This analysis shows that the homeodomain containing SO gene product is involved in the specification of the larval and adult visual system development during embryogenesis.
The axr2-1 mutation of Arabidopsis thaliana is a gain-of-function mutation that disrupts an early step in auxin response.
Authors: Timpte C , Wilson A K , Estelle M 
Published: January 2021

Abstract
The dominant axr2-1 mutation of Arabidopsis thaliana confers resistance to the plant hormones auxin, ethylene, and abscisic acid. In addition, axr2-1 has pleiotropic effects on plant morphology which include gravitropic defects in roots, hypocotyls and inflorescences of axr2-1 plants. Two genetic screens were conducted to isolate new mutations at the AXR2 locus. First, axr2-1 pollen was gamma-irradiated, crossed onto wild-type plants, and the M1 progeny screened for loss of the axr2-1 phenotype. Large deletions of the axr2-1 region on chromosome 3 resulted; however, none of these deletions appeared to be heritable. In the second, M2 seed obtained from axr2-1 gl-1 plants was screened for reversion of the axr2-1 phenotype. One revertant line, axr2-r3, has a distinctive phenotype caused by a second mutation at the axr2 locus. To learn more about the nature of the axr2-1 mutation, the effects of varying the ratio of wild-type to mutant copies of the AXR2 gene were examined by comparing plants of the following genotypes: +/+, +/+/+, axr2-1/axr2-1, axr2-1/+ and axr2-1/+/+. Additionally, accumulation of transcripts from the auxin-inducible SAUR-AC1 gene was examined to determine the response of wild-type and mutant plants to auxin. Wild-type seedlings and mature plants accumulate transcripts with auxin treatment. In contrast, axr2-1 tissue does not accumulate SAUR-AC1 transcripts in response to auxin. Taken together, these results indicate that axr2-1 is a neomorphic or hypermorphic mutation that disrupts an early step in an auxin response pathway.
Mutator insertions in an intron of the maize knotted1 gene result in dominant suppressible mutations.
Authors: Greene B , Walko R , Hake S 
Published: January 2021

Abstract
The knotted1 (kn1) locus of maize is defined by a series of dominant mutations affecting leaf development. We recovered 10 additional mutant alleles in lines containing active Mutator transposable elements. Nine of these alleles contain Mu1 or Mu8 elements inserted within a 310-bp region of the kn1 third intron. All five Mu8 insertions are in the same orientation whereas both orientations of Mu1 were recovered. Northern analysis showed that ectopic expression of kn1 within developing leaves is correlated with the mutant phenotype for the four alleles analyzed. Transcript size was not altered. The effect of Mu activity, as measured by the extent of Mu element methylation or by the presence of the autonomous MuDR element, was investigated for two alleles. Kn1-mum2, containing a Mu8 element, and Kn1-mum7, containing a Mu1 element, required Mu activity for the knotted phenotype. We examined the effect of Mu activity on ectopic kn1 expression in Kn1-mum2 and found that the transcript was present in leaves of Mu active individuals only. We discuss possible mechanisms by which Mu activity could condition kn1 gene expression.
Constructing confidence intervals for QTL location.
Authors: Mangin B , Goffinet B , Rebaï A 
Published: January 2021

Abstract
We describe a method for constructing the confidence interval of the QTL location parameter. This method is developed in the local asymptotic framework, leading to a linear model at each position of the putative QTL. The idea is to construct a likelihood ratio test, using statistics whose asymptotic distribution does not depend on the nuisance parameters and in particular on the effect of the QTL. We show theoretical properties of the confidence interval built with this test, and compare it with the classical confidence interval using simulations. We show in particular, that our confidence interval has the correct probability of containing the true map location of the QTL, for almost all QTLs, whereas the classical confidence interval can be very biased for QTLs having small effect.
Constraints on intron evolution in the gene encoding the myosin alkali light chain in Drosophila.
Authors: Leicht B G , Muse S V , Hanczyc M , Clark A G 
Published: January 2021

Abstract
Interspecific comparisons of intron sequences reveal conserved blocks of invariant nucleotides and several other departures from the strictly neutral model of molecular evolution. To distinguish the past action of evolutionary forces in introns known to have regulatory information, we examined nucleotide sequence variation at 991 sites in a random sample of 16 Drosophila melanogaster alleles of the gene encoding the myosin alkali light chain (Mlc1). The Mlc1 gene of D. melanogaster encodes two MLC1 isoforms via developmentally regulated alternative pre-mRNA splicing. Analyses of these data reveal that introns 4 and 5, which flank the alternatively spliced exon 5, have reduced levels of both intraspecific polymorphism and interspecific divergence relative to intron 3. No polymorphism was observed in any of the exons examined in D. melanogaster. A genealogical analysis clearly demonstrates the occurrence of intragenic recombination in the ancestral history of Mlc1. Recombination events are estimated to be 13 times more likely than mutation events over the span of the sequenced region. Although there is little evidence for pairwise linkage disequilibrium in the Mlc1 region, higher order disequilibrium does seem to be present in the 5' half of the portion of the gene that was examined. Predictions of the folding free energy of the pre-mRNA reveal that sampled alleles have a significantly higher (less stable) free energy than do randomly permuted sequences. These results are consistent with the hypothesis that introns surrounding an alternatively spliced exon are subjected to additional constraints, perhaps due to specific aspects of secondary structure required for appropriate splicing of the pre-mRNA molecule.
Identification of target genes regulated by homeotic proteins in Drosophila melanogaster through genetic selection of Ultrabithorax protein-binding sites in yeast.
Authors: Mastick G S , McKay R , Oligino T , Donovan K , López A J 
Published: January 2021

Abstract
A method based on the transcriptional activation of a selectable reporter in yeast cells was used to identify genes regulated by the Ultrabithorax homeoproteins in Drosophila melanogaster. Fifty-three DNA fragments that can mediate activation by UBX isoform Ia in this test were recovered after screening 15% of the Drosophila genome. Half of these fragments represent single-copy sequences in the genome. Six single-copy fragments were investigated in detail, and each was found to reside near a transcription unit whose expression in the embryo is segmentally modulated as expected for targets of homoeotic genes. Four of these putative target genes are expressed in patterns that suggest roles in the development of regional specializations within mesoderm derivatives; in three cases these expression patterns depend on Ultrabithorax function. Extrapolation from this pilot study indicates that 85-170 candidate target genes can be identified by screening the entire Drosophila genome with UBX isoform Ia. With appropriate modifications, this approach should be applicable to other transcriptional regulators in diverse organisms.
Transduction, restriction and recombination patterns in Escherichia coli.
Authors: McKane M , Milkman R 
Published: January 2021

Abstract
Chromosomal DNA from several Escherichia coli reference (ECOR) strains was transduced by bacteriophage P1 into E. coli strain K12 W3110 trpA33. Recombination patterns of the transductants were determined by restriction fragment length polymorphism over a 40-kb region centering on a single marker (trpA+) in the tryptophan operon. These experiments demonstrate that transduction between different strains of E. coli can result in recombinational replacements that are small in comparison to the entrant molecule (replacements average 8-14 kb, whereas P1 packages approximately 100 kb) often in a series of discrete segments. The transduction patterns generated resemble the natural mosaic sequence patterns of the ECOR strains described in previous work. Extensive polymorphisms in the restriction-modification systems of the ECOR strains are a possible explanation for the sequence patterns in nature. To test this possibility two transductants were back-transduced into strain K12 W3110 trpA33. The resulting patterns were strikingly different from the original transductions. The size of the replacements was greater, and no multiple replacements were observed, suggesting a role for restriction-modification systems in the transduction patterns and perhaps for the mosaic sequence patterns in nature.
Multiple pathways for homologous recombination in Saccharomyces cerevisiae.
Authors: Rattray A J , Symington L S 
Published: January 2021

Abstract
The genes in the RAD52 epistasis group of Saccharomyces cerevisiae are necessary for most mitotic and meiotic recombination events. Using an intrachromosomal inverted-repeat assay, we previously demonstrated that mitotic recombination of this substrate is dependent upon the RAD52 gene. In the present study the requirement for other genes in this epistasis group for recombination of inverted repeats has been analyzed, and double and triple mutant strains were examined for their epistatic relationships. The majority of recombination events are mediated by a RAD51-dependent pathway, where the RAD54, RAD55 and RAD57 genes function downstream of RAD51. Cells mutated in RAD55 or RAD57 as well as double mutants are cold-sensitive for inverted-repeat recombination, whereas a rad51 rad55 rad57 triple mutant is not. The RAD1 gene is not required for inverted-repeat recombination but is able to process spontaneous DNA lesions to produce recombinant products in the absence of RAD51. Furthermore, there is still considerably more recombination in rad1 rad51 mutants than in rad52 mutants, indicating the presence of another, as yet unidentified, recombination pathway.
Extra telomeres, but not internal tracts of telomeric DNA, reduce transcriptional repression at Saccharomyces telomeres.
Authors: Wiley E A , Zakian V A 
Published: January 2021

Abstract
Yeast telomeric DNA is assembled into a nonnucleosomal chromatin structure known as the telosome, which is thought to influence the transcriptional repression of genes placed in its vicinity, a phenomenon called telomere position effect (TPE). The product of the RAP1 gene, Rap1p, is a component of the telosome. We show that the fraction of cells exhibiting TPE can be substantially reduced by expressing large amounts of a deletion derivative of Rap1p that is unable to bind DNA, called Rap1 delta BBp, or by introducing extra telomeres on a linear plasmid, presumably because both compete in trans with telomeric chromatin for factor(s) important for TPE. This reduction in TPE, observed in three different strains, was demonstrated for two different genes, each assayed at a different telomere. In contrast, the addition of internal tracts of telomeric DNA on a circular plasmid had very little effect on TPE. The product of the SIR3 gene, Sir3p, appears to be limiting for TPE. Overexpression of Sir3p completely suppressed the reduction in TPE observed with expression of Rap1 delta BBp, but did not restore high levels of TPE to cells with extra telomeres. These results suggest that extra telomeres must titrate a factor other than Sir3p that is important for TPE. These results also provide evidence for a terminus-specific binding factor that is a factor with a higher affinity for DNA termini than for nonterminal tracts of telomeric DNA and indicate that this factor is important for TPE.
Effective size of populations under selection.
Authors: Santiago E , Caballero A 
Published: January 2021

Abstract
Equations to approximate the effective size (Ne) of populations under continued selection are obtained that include the possibility of partial full-sib mating and other systems such as assortative mating. The general equation for the case of equal number of sexes and constant number of breeding individuals (N) is Ne = 4N/[2(1 - alpha I) + (Sk2 + 4Q2C2) (1 + alpha I + 2 alpha O)], where Sk2 is the variance of family size due to sampling without selection, C2 is the variance of selective advantages among families (the squared coefficient of variation of the expected number of offspring per family), alpha I is the deviation from Hardy-Weinberg proportions, alpha O is the correlation between genes of male and female parents, and Q2 is the term accounting for the cumulative effect of selection on an inherited trait. This is obtained as Q = 2/[2 - G(1 + r)], where G is the remaining proportion of genetic variance in selected individuals and r is the correlation of the expected selective values of male and female parents. The method is also extended to the general case of different numbers of male and female parents. The predictive value of the formulae is tested under a model of truncation selection with the infinitesimal model of gene effects, where C2 and G are a function of the selection intensity, the heritability and the intraclass correlation of sibs. Under random mating r = alpha I = -1/(N - 1) and alpha O = 0. Under partial full-sib mating with an average proportion beta of full-sib matings per generation, r approximately beta and alpha O approximately alpha I approximately beta/(4 - 3 beta). The prediction equation is compared to other approximations based on the long-term contributions of ancestors to descendants. Finally, based on the approach followed, a system of mating (compensatory mating) is proposed to reduce rates of inbreeding without loss of response in selection programs in which selected individuals from the largest families are mated to those from the smallest families.
Temporal allele frequency change and estimation of effective size in populations with overlapping generations.
Authors: Jorde P E , Ryman N 
Published: January 2021

Abstract
In this paper we study the process of allele frequency change in finite populations with overlapping generations with the purpose of evaluating the possibility of estimating the effective size from observations of temporal frequency shifts of selectively neutral alleles. Focusing on allele frequency changes between successive cohorts (individuals born in particular years), we show that such changes are not determined by the effective population size alone, as they are when generations are discrete. Rather, in populations with overlapping generations, the amount of temporal allele frequency change is dependent on the age-specific survival and birth rates. Taking this phenomenon into account, we present an estimator for effective size that can be applied to populations with overlapping generations.
The sep1 mutant of Saccharomyces cerevisiae arrests in pachytene and is deficient in meiotic recombination.
Authors: Tishkoff D X , Rockmill B , Roeder G S , Kolodner R D 
Published: January 2021

Abstract
Strand exchange protein 1 (Sep1) from Saccharomyces cerevisiae promotes homologous pairing of DNA in vitro and sep1 mutants display pleiotropic phenotypes in both vegetative and meiotic cells. In this study, we examined in detail the ability of the sep1 mutant to progress through meiosis I prophase and to undergo meiotic recombination. In meiotic return-to-growth experiments, commitment to meiotic recombination began at the same time in wild type and mutant; however, recombinants accumulated at decreased rates in the mutant. Gene conversion eventually reached nearly wild-type levels, whereas crossing over reached 15-50% of wild type. In an assay of intrachromosomal pop-out recombination, the sep1, dmc1 and rad51 single mutations had only small effects; however, pop-out recombination was virtually eliminated in the sep1 dmc1 and sep1 rad51 double mutants, providing evidence for multiple recombination pathways. Analysis of meiotic recombination intermediates indicates that the sep1 mutant is deficient in meiotic double-strand break repair. In a physical assay, the formation of mature reciprocal recombinants in the sep1 mutant was delayed relative to wild type and ultimately reached only 50% of the wild-type level. Electron microscopic analysis of meiotic nuclear spreads indicates that the sep1 delta mutant arrests in pachytene, with apparently normal synaptonemal complex. This arrest is RAD9-independent. We hypothesize that the Sep1 protein participates directly in meiotic recombination and that other strand exchange enzymes, acting in parallel recombination pathways, are able to substitute partially for the absence of the Sep1 protein.
Complete sequence of a sea lamprey (Petromyzon marinus) mitochondrial genome: early establishment of the vertebrate genome organization.
Authors: Lee W J , Kocher T D 
Published: January 2021

Abstract
The complete nucleotide sequence of a sea lamprey (Petromyzon marinus) mitochondrial genome has been determined. The lamprey genome is 16,201 bp in length and contains genes for 13 proteins, two rRNAs, 22 tRNAs and two major noncoding regions. The order and transcriptional polarities of protein-coding genes are basically identical to those of other chordate mtDNAs, demonstrating that the common mitochondrial gene organization of vertebrates was established at an early stage of vertebrate evolution. The two major noncoding regions are separated by two tRNA genes. The first region probably functions as the control region because it contains distinctive conserved sequence blocks (CSB-II and III) common to other vertebrate control regions. The central conserved domain observed in other vertebrate control regions is not found in the lamprey, suggesting that it is a recently evolved functional domain in vertebrates. Noncoding segments are not found in the expected position of the origin of replication for the second strand, suggesting either that one of the tRNA genes has a dual function or that the second noncoding region may function as the second-strand origin. The base composition at the wobble positions of fourfold degenerate codon families is highly biased toward thymine (32.7%). Values of GC- and AT-skew are typical of vertebrate mitochondrial genomes.