bluuebunny/crossref_metadata_2025_split huggingface dataset:
Insertional mutations in the yeast HOP1 gene: evidence for multimeric assembly in meiosis.
Authors: Friedman D B , Hollingsworth N M , Byers B 
Published: January 2021

Abstract
The HOP1 gene of Saccharomyces cerevisiae has been shown to play an important role in meiotic synapsis. In this study we analyzed the mechanism of this function by phenotypic characterization of novel in-frame linker-insertion mutations located at various sites throughout the HOP1 coding sequence. Among 12 mutations found to cause defects in meiotic recombination and spore viability, three were temperature-sensitive for the spore viability defect. Although substantial meiotic recombination was found for these conditional alleles at the restrictive temperature, the level of exchange measured in spo13 meiosis was reduced in some of the monitored intervals, indicating that nondisjunction resulting from a deficit in crossing over could account for SPO13 spore inviability. Intragenic complementation between linker-insertion alleles was assessed by testing the viability of spores generated from heteroallelic diploids after SPO13 meiosis. Complex patterns of complementation and enhancement of the spore-inviability phenotype indicate that HOP1 functions in a multimeric complex. In addition, the ability of alleles which map near the carboxyl terminus to complement several other alleles provides evidence for a functional domain in this region of the protein. Two previously identified multicopy suppressors of the conditional hop1-628ts allele were tested for their effects in cells bearing the linker-insertion hop1 alleles. Overexpression of REC104 from a 2 mu plasmid was shown to enhance the spore viability of every allele tested, including a hop1 disruption allele. On the other hand, suppression by overexpression of RED1 from a 2 mu plasmid was found only for allele hop1-628ts. Surprisingly, similar overexpression of RED1 in strains bearing several other conditional hop1 linker-insertion alleles caused enhanced spore lethality. This finding, in conjunction with the evidence for a carboxy-terminal domain, provides new insight into the nature of interactions between the HOP1 and RED1 products in meiosis.
Identification and characterization of Aspergillus nidulans mutants defective in cytokinesis.
Authors: Harris S D , Morrell J L , Hamer J E 
Published: January 2021

Abstract
Filamentous fungi undergo cytokinesis by forming crosswalls termed septa. Here, we describe the genetic and physiological controls governing septation in Aspergillus nidulans. Germinating conidia do not form septa until the completion of their third nuclear division. The first septum is invariantly positioned at the basal end of the germ tube. Block-and-release experiments of nuclear division with benomyl or hydroxyurea, and analysis of various nuclear division mutants demonstrated that septum formation is dependent upon the third mitotic division. Block-and-release experiments with cytochalasin A and the localization of actin in germlings by indirect immunofluorescence showed that actin participated in septum formation. In addition to being concentrated at the growing hyphal tips, a band of actin was also apparent at the site of septum formation. Previous genetic analysis in A. nidulans identified four genes involved in septation (sepA-D). We have screened a new collection of temperature sensitive (ts) mutants of A. nidulans for strains that failed to form septa at the restrictive temperature but were able to complete early nuclear divisions. We identified five new genes designated sepE, G, H, I and J, along with one additional allele of a previously identified septation gene. On the basis of temperature shift experiments, nuclear counts and cell morphology, we sorted these cytokines mutants into three phenotypic classes. Interestingly, one class of mutants fails to form septa and fails to progress past the third nuclear division. This class of mutants suggests the existence of a regulatory mechanism in A. nidulans that ensures the continuation of nuclear division following the initiation of cytokinesis.
Change in genetic variance under selection in a self-fertilizing population.
Authors: Hayashi T , Ukai Y 
Published: January 2021

Abstract
In this study we show how the genetic variance of a quantitative trait changes in a self-fertilizing population under repeated cycles of truncation selection, with the analysis based on the infinitesimal model in which it is assumed that the trait is determined by an infinite number of unlinked loci without epistasis. The genetic variance is reduced not as a consequence of the genotypic frequency change but due to the build-up of linkage disequilibrium under truncation selection in this model. We assume that the order of the genotypic contribution from each locus is n-1/2, where n is the number of loci involved, and investigate the change in linkage disequilibrium resulting from selection and self-fertilization using genotypic frequency dynamics in order to analyze the change in the genetic variance. Our analysis gives recurrence relations of genetic variance among the succeeding generations for the three cases of gene action, i.e., purely additive action, pure dominance without additive effect and the presence of both additive effect and dominance, respectively. Numerical examples are also given as a check on the recurrence formulas.
Unusual properties of regulatory DNA from the Drosophila engrailed gene: three "pairing-sensitive" sites within a 1.6-kb region.
Authors: Kassis J A 
Published: January 2021

Abstract
We have previously shown that a 2-kb fragment of engrailed DNA can suppress expression of a linked marker gene, white, in the P element vector CaSpeR. This suppression is dependent on the presence of two copies of engrailed DNA-containing P elements (P[en]) in proximity in the Drosophila genome (either in cis or in trans). In this study, the 2-kb fragment was dissected and found to contain three fragments of DNA which could mediate white suppression [called "pairing-sensitive sites" (PS)]. A PS site was also identified in regulatory DNA from the Drosophila escargot gene. The eye colors of six different P[en] insertions in the escargot gene suggest an interaction between P[en]-encoded and genome-encoded PS sites. I hypothesize that white gene expression from P[en] is repressed by the formation of a protein complex which is initiated at the engrailed PS sites and also requires interactions with flanking genomic DNA. Genes were sought which influence the function of PS sites. Mutations in some Polycomb and trithorax group genes were found to affect the eye color from some P[en] insertion sites. However, different mutations affected expression from different P[en] insertion sites and no one mutation was found to affect expression from all P[en] insertion sites examined. These results suggest that white expression from P[en] is not directly regulated by members of the Polycomb and trithorax group genes, but in some cases can be influenced by them. I propose that engrailed PS sites normally act to promote interactions between distantly located engrailed regulatory sites and the engrailed promoter.
Variegated phenotype and developmental methylation changes of a maize allele originating from epimutation.
Authors: Das O P , Messing J 
Published: January 2021

Abstract
Two instances of genetic transmission of spontaneous epimutation of the maize P-rr gene were identified. Transmission gave rise to two similar, moderately stable alleles, designated P-pr-1 and P-pr-2, that exhibited Mendelian behavior. Both isolates of P-pr conditioned a variable and variegated phenotype, unlike the uniform pigmentation conditioned by P-rr. Extensive genomic analysis failed to reveal insertions, deletions or restriction site polymorphisms between the new allele and its progenitor. However, methylation of the P gene was increased in P-pr relative to P-rr, and was greatly reduced (though not lost) in a revertant to uniform pigmentation. Variability in pigmentation conditioned by P-pr correlated with variability in transcript levels of the P gene, and both correlated inversely with variability in its methylation. Part of the variability in methylation could be accounted for by a developmental decrease in methylation in all tissues of plants carrying P-pr. We hypothesize that the variegated phenotype results from a general epigenetic pathway which causes a progressive decrease in methylation and increase in expression potential of the P gene as a function of cell divisions in each meristem of the plant. This renders all tissues chimeric for a functional gene; chimerism is visualized as variegation only in pericarp due to the tissue specificity of P gene expression. Therefore, this allele that originates from epimutation may exemplify an epigenetic mechanism for variegation in maize.
Mapping quantitative trait loci in crosses between outbred lines using least squares.
Authors: Haley C S , Knott S A , Elsen J M 
Published: January 2021

Abstract
The use of genetic maps based upon molecular markers has allowed the dissection of some of the factors underlying quantitative variation in crosses between inbred lines. For many species crossing inbred lines is not a practical proposition, although crosses between genetically very different outbred lines are possible. Here we develop a least squares method for the analysis of crosses between outbred lines which simultaneously uses information from multiple linked markers. The method is suitable for crosses where the lines may be segregating at marker loci but can be assumed to be fixed for alternative alleles at the major quantitative trait loci (QTLs) affecting the traits under analysis (e.g., crosses between divergent selection lines or breeds with different selection histories). The simultaneous use of multiple markers from a linkage group increases the sensitivity of the test statistic, and thus the power for the detection of QTLs, compared to the use of single markers or markers flanking an interval. The gain is greater for more closely spaced markers and for markers of lower information content. Use of multiple markers can also remove the bias in the estimated position and effect of a QTL which may result when different markers in a linkage group vary in their heterozygosity in the F1 (and thus in their information content) and are considered only singly or a pair at a time. The method is relatively simple to apply so that more complex models can be fitted than is currently possible by maximum likelihood. Thus fixed effects of background genotype can be fitted simultaneously with the exploration of a single linkage group which will increase the power to detect QTLs by reducing the residual variance. More complex models with several QTLs in the same linkage group and two-locus interactions between QTLs can similarly be examined. Thus least squares provides a powerful tool to extend the range of crosses from which QTLs can be dissected whilst at the same time allowing flexible and realistic models to be explored.
Complex frameshift mutations mediated by plasmid pKM101: mutational mechanisms deduced from 4-aminobiphenyl-induced mutation spectra in Salmonella.
Authors: Levine J G , Schaaper R M , DeMarini D M 
Published: January 2021

Abstract
We used colony probe hybridization and polymerase chain reaction/DNA sequence analysis to determine the mutations in approximately 2,400 4-aminobiphenyl (4-AB) +S9-induced revertants of the -1 frameshift allele hisD3052 and of the base-substitution allele hisG46 of Salmonella typhimurium. Most of the mutations occurred at sites containing guanine, which is the primary base at which 4-AB forms DNA adducts. A hotspot mutation involving the deletion of a CG or GC within the sequence CGCGCGCG accounted for 100 and 99.9%, respectively, of the reversion events at the hisD3052 allele in the pKM101 plasmid-minus strains TA1978 (uvr+) and TA1538 (delta uvrB). In strain TA98 (delta uvrB, pKM101), which contained the SOS DNA repair system provided by the pKM101 plasmid, approximately 85% of the revertants also contained the hotspot deletion; the remaining approximately 15% contained one of two types of mutations: (1) complex frameshifts that can be described as a -2 or +1 frameshift and an associated base substitution and (2) deletions of the CC or GG sequences that flank the hotspot site (CCGCGCGCGG). We propose a misincorporation/slippage model to account for these mutations in which (1) pKM101-mediated misincorporation and translesion synthesis occurs across a 4-AB-adducted guanine; (2) the instability of such a mispairing and/or the presence of the adduct leads to strand slippage in a run of repeated bases adjacent to the adducted guanine; and (3) continued DNA synthesis from the slipped intermediate produces a frameshift associated with a base substitution. This model readily accounts for the deletion of the CC or GG sequences flanking the hotspot site, indicating that these mutations are, in fact, complex mutations in disguise (i.e., cryptic complex frameshifts). The inferred base-substitution specificity associated with the complex frameshifts at the hisD3052 allele (primarily G.C--&gt;T.A transversions) is consistent with the finding that 4-AB induced primarily G.C--&gt;T.A transversions at the hisG46 base-substitution allele. The model also provides a framework for understanding the different relative mutagenic potencies of 4-AB at the two alleles in the various DNA repair backgrounds of Salmonella.
A screen for nonconditional dauer-constitutive mutations in Caenorhabditis elegans.
Authors: Malone E A , Thomas J H 
Published: January 2021

Abstract
In Caenorhabditis elegans, formation of the developmentally arrested dauer larva is induced by high levels of a constitutively secreted pheromone. Synergy between two groups of incompletely penetrant dauer-constitutive (Daf-c) mutations has recently led to a proposal that these two groups of genes are partially redundant and function in two parallel pathways that regulate dauer formation. A possible weakness in this reasoning is that the mutations used to identify the synergy were specifically obtained as incompletely penetrant mutations. Here we use screens to identify new Daf-c alleles without any requirement for partial penetrance. Nevertheless, 22 of the 25 new mutations are incompletely penetrant mutations in 6 previously identified genes. Among these are mutations in daf-8 and daf-19, genes for which only one mutation had been previously identified. Also included in this group are three daf-1 alleles that do not exhibit the maternal rescue characteristic of other daf-1 alleles. Two of the 25 new mutations are fully penetrant and are alleles of daf-2, the one gene in which a fully penetrant mutation had been found earlier. Finally, one of the 25 new mutations is semidominant, temperature-sensitive, and identifies a new gene, daf-28. The results demonstrate that an incompletely penetrant Daf-c phenotype is characteristic of mutations in most Daf-c genes other than daf-2. This finding strengthens the hypothesis that a branched genetic pathway controls dauer formation.
Synonymous codon usage in Drosophila melanogaster: natural selection and translational accuracy.
Authors: Akashi H 
Published: January 2021

Abstract
I present evidence that natural selection biases synonymous codon usage to enhance the accuracy of protein synthesis in Drosophila melanogaster. Since the fitness cost of a translational misincorporation will depend on how the amino acid substitution affects protein function, selection for translational accuracy predicts an association between codon usage in DNA and functional constraint at the protein level. The frequency of preferred codons is significantly higher at codons conserved for amino acids than at nonconserved codons in 38 genes compared between D. melanogaster and Drosophila virilis or Drosophila pseudoobscura (Z = 5.93, P &lt; 10(-6)). Preferred codon usage is also significantly higher in putative zinc-finger and homeodomain regions than in the rest of 28 D. melanogaster transcription factor encoding genes (Z = 8.38, P &lt; 10(-6)). Mutational alternatives (within-gene differences in mutation rates, amino acid changes altering codon preference states, and doublet mutations at adjacent bases) do not appear to explain this association between synonymous codon usage and amino acid constraint.
Polygenic mutation in Drosophila melanogaster: estimates from response to selection of inbred strains.
Authors: Mackay T F , Fry J D , Lyman R F , Nuzhdin S V 
Published: January 2021

Abstract
Replicated divergent artificial selection for abdominal and sternopleural bristle number from a highly inbred strain of Drosophila melanogaster resulted in an average divergence after 125 generations of selection of 12.0 abdominal and 8.2 sternopleural bristles from the accumulation of new mutations affecting bristle number. Responses to selection were highly asymmetrical, with greater responses for low abdominal and high sternopleural bristle numbers. Estimates of VM, the mutational variance arising per generation, based on the infinitesimal model and averaged over the responses to the first 25 generations of selection, were 4.32 x 10(-3) VE for abdominal bristle number and 3.66 x 10(-3) VE for sternopleural bristle number, where VE is the environmental variance. Based on 10 generations of divergent selection within lines from generation 93, VM for abdominal bristle number was 6.75 x 10(-3) VE and for sternopleural bristle number was 5.31 x 10(-3) VE. However, estimates of VM using the entire 125 generations of response to selection were lower and generally did not fit the infinitesimal model largely because the observed decelerating responses were not compatible with the predicted increasing genetic variance over time. These decelerating responses, periods of response in the opposite direction to artificial selection, and rapid responses to reverse selection all suggest new mutations affecting bristle number on average have deleterious effects on fitness. Commonly observed periods of accelerated responses followed by long periods of stasis suggest a leptokurtic distribution of mutational effects for bristles.
Identification of genes required for normal pheromone-induced cell polarization in Saccharomyces cerevisiae.
Authors: Chenevert J , Valtz N , Herskowitz I 
Published: January 2021

Abstract
In response to mating pheromones, cells of the yeast Saccharomyces cerevisiae adopt a polarized "shmoo" morphology, in which the cytoskeleton and proteins involved in mating are localized to a cell-surface projection. This polarization is presumed to reflect the oriented morphogenesis that occurs between mating partners to facilitate cell and nuclear fusion. To identify genes involved in pheromone-induced cell polarization, we have isolated mutants defective in mating to an enfeebled partner and studied a subset of these mutants. The 34 mutants of interest are proficient for pheromone production, arrest in response to pheromone, mate to wild-type strains, and exhibit normal cell polarity during vegetative growth. The mutants were divided into classes based on their morphological responses to mating pheromone. One class is unable to localize cell-surface growth in response to mating factor and instead enlarges in a uniform manner. These mutants harbor special alleles of genes required for cell polarization during vegetative growth, BEM1 and CDC24. Another class of mutants forms bilobed, peanut-like shapes when treated with pheromone and defines two genes, PEA1 and PEA2. PEA1 is identical to SPA2. A third class forms normally shaped but tiny shmoos and defines the gene TNY1. A final group of mutants exhibits apparently normal shmoo morphology. The nature of their mating defect is yet to be determined. We discuss the possible roles of these gene products in establishing cell polarity during mating.
Analysis of a detailed genetic linkage map of Lactuca sativa (lettuce) constructed from RFLP and RAPD markers.
Authors: Kesseli R V , Paran I , Michelmore R W 
Published: January 2021

Abstract
A detailed genetic map has been constructed from the F2 population of a single intraspecific cross of Lactuca sativa (n = 9). It comprises 319 loci, including 152 restriction fragment length polymorphism (RFLP), 130 random amplified polymorphic DNA (RAPD), 7 isozyme, 19 disease resistance, and 11 morphological markers. Thirteen major, four minor linkage groups and several unlinked markers are identified for this genome which is estimated to be approximately 1950 cM. RFLP and RAPD markers show similar distributions throughout the genome and identified similar levels of polymorphism. RAPD loci were much quicker to identify but more difficult to order. Procedures for generating accurate genetic maps and their limitations are described.
Analysis of autoregulation at the level of pre-mRNA splicing of the suppressor-of-white-apricot gene in Drosophila.
Authors: Zachar Z , Chou T B , Kramer J , Mims I P , Bingham P M 
Published: January 2021

Abstract
The Drosophila suppressor-of-white-apricot [su(wa)] protein regulates/modulates at least two somatic RNA processing events. It is a potent regulator of its own expression. We report here new studies of this autoregulatory circuit. Among other things, our studies show the following. First, new evidence that su(wa) expression is autoregulated at the level of pre-mRNA splicing is reported. su(wa) protein represses accumulation of the fully spliced su(wa) mRNA encoding it and promotes accumulation of high levels of incompletely spliced su(wa) pre-mRNA. Second, the fully spliced su(wa) mRNA is sufficient for all known su(wa) genetic functions indicating that it encodes the sole su(wa) protein. Third, the incompletely spliced su(wa) pre-mRNAs resulting from autoregulation are not translated (probably as a result of nuclear retention) and apparently represent nonfunctional by-products. Fourth, the special circumstances of su(wa) expression during oogenesis allows maternal deposition exclusively of fully spliced su(wa) mRNA. Fifth, su(wa) protein immunolocalizes to nuclei consistent with its being a direct regulator of pre-mRNA processing. We discuss the implications of our results for mechanisms of splicing regulation and for developmental control of su(wa) expression.
Recovery of dominant, autosomal flightless mutants of Drosophila melanogaster and identification of a new gene required for normal muscle structure and function.
Authors: Cripps R M , Ball E , Stark M , Lawn A , Sparrow J C 
Published: January 2021

Abstract
To identify further mutations affecting muscle function and development in Drosophila melanogaster we recovered 22 autosomal dominant flightless mutations. From these we have isolated eight viable and lethal alleles of the muscle myosin heavy chain gene, and seven viable alleles of the indirect flight muscle (IFM)-specific Act88F actin gene. The Mhc mutations display a variety of phenotypic effects, ranging from reductions in myosin heavy chain content in the indirect flight muscles only, to reductions in the levels of this protein in other muscles. The Act88F mutations range from those which produce no stable actin and have severely abnormal myofibrillar structure, to those which accumulate apparently normal levels of actin in the flight muscles but which still have abnormal myofibrils and fly very poorly. We also recovered two recessive flightless mutants on the third chromosome. The remaining five dominant flightless mutations are all lethal alleles of a gene named lethal(3)Laker. The Laker alleles have been characterized and the gene located in polytene bands 62A10,B1-62B2,4. Laker is a previously unidentified locus which is haplo-insufficient for flight. In addition, adult wild-type heterozygotes and the lethal larval trans-heterozygotes show abnormalities of muscle structure indicating that the Laker gene product is an important component of muscle.