bluuebunny/crossref_metadata_2025_split huggingface dataset:
Nonlinear Developmental Processes as Sources of Dominance
Authors: Gilchrist Michael A , Nijhout H Fredrik 
Published: April 2021

Abstract
Phenotypes are the products of developmental processes whose dynamics are controlled by genes. In many developmental processes there is a nonlinear relationship between genetic variation and phenotypic variation. These nonlinear relationships can result in the emergence of dominance among alleles that control the developmental process. We explore the properties of dominance relationships in a simple developmental system consisting of a diffusion-gradient-threshold mechanism commonly deployed in pattern formation. We show that a single nonlinear process (diffusion) within this integrated mechanism leads to the emergence of dominance in all components of the mechanism. Unlike the situation in metabolic pathways, where new mutations are most likely to be recessive, the structure of the nonlinearities in this developmental mechanism is such that in certain circumstances new mutations are equally likely to be dominant or recessive. Although the dominance we observe in this system is the result of a physiological process, we also find that dominance can evolve by microevolutionary mechanisms and thus are able to reconcile the opposing views of Fisher and Wright on dominance.
The Ras/PKA Signaling Pathway ofSaccharomyces cerevisiaeExhibits a Functional Interaction With the Sin4p Complex of the RNA Polymerase II Holoenzyme
Authors: Howard Susie C , Chang Ya-Wen , Budovskaya Yelena V , Herman Paul K 
Published: April 2021

AbstractSaccharomyces cerevisiae cells enter into the G0-like resting state, stationary phase, in response to specific types of nutrient limitation. We have initiated a genetic analysis of this resting state and have identified a collection of rye mutants that exhibit a defective transcriptional response to nutrient deprivation. These transcriptional defects appear to disrupt the control of normal growth because the rye mutants are unable to enter into a normal stationary phase upon nutrient deprivation. In this study, we examined the mutants in the rye1 complementation group and found that rye1 mutants were also defective for stationary phase entry. Interestingly, the RYE1 gene was found to be identical to SIN4, a gene that encodes a component of the yeast Mediator complex within the RNA polymerase II holoenzyme. Moreover, mutations that affected proteins within the Sin4p module of the Mediator exhibited specific genetic interactions with the Ras protein signaling pathway. For example, mutations that elevated the levels of Ras signaling, like RAS2val19, were synthetic lethal with sin4. In all, our data suggest that specific proteins within the RNA polymerase II holoenzyme might be targets of signal transduction pathways that are responsible for coordinating gene expression with cell growth.
Direct Estimate of the Mutation Rate and the Distribution of Fitness Effects in the Yeast Saccharomyces cerevisiae
Authors: Wloch Dominika M , Szafraniec Krzysztof , Borts Rhona H , Korona Ryszard 
Published: April 2021

Abstract
Estimates of the rate and frequency distribution of deleterious effects were obtained for the first time by direct scoring and characterization of individual mutations. This was achieved by applying tetrad analysis to a large number of yeast clones. The genomic rate of spontaneous mutation deleterious to a basic fitness-related trait, that of growth rate, was U = 1.1 × 10−3 per diploid cell division. Extrapolated to the fruit fly and humans, the per generation rate would be 0.074 and 0.92, respectively. This is likely to be an underestimate because single mutations with selection coefficients s &lt; 0.01 could not be detected. The distribution of s ≥ 0.01 was studied both for spontaneous and induced mutations. The latter were induced by ethyl methanesulfonate (EMS) or resulted from defective mismatch repair. Lethal changes accounted for ~30–40% of the scored mutations. The mean s of nonlethal mutations was fairly high, but most frequently its value was between 0.01 and 0.05. Although the rate and distribution of very small effects could not be determined, the joint share of such mutations in decreasing average fitness was probably no larger than ~1%.
Genes Involved in Sister Chromatid Separation and Segregation in the Budding Yeast Saccharomyces cerevisiae
Authors: Biggins Sue , Bhalla Needhi , Chang Amy , Smith Dana L , Murray Andrew W 
Published: April 2021

Abstract
Accurate chromosome segregation requires the precise coordination of events during the cell cycle. Replicated sister chromatids are held together while they are properly attached to and aligned by the mitotic spindle at metaphase. At anaphase, the links between sisters must be promptly dissolved to allow the mitotic spindle to rapidly separate them to opposite poles. To isolate genes involved in chromosome behavior during mitosis, we microscopically screened a temperature-sensitive collection of budding yeast mutants that contain a GFP-marked chromosome. Nine LOC (loss of cohesion) complementation groups that do not segregate sister chromatids at anaphase were identified. We cloned the corresponding genes and performed secondary tests to determine their function in chromosome behavior. We determined that three LOC genes, PDS1, ESP1, and YCS4, are required for sister chromatid separation and three other LOC genes, CSE4, IPL1, and SMT3, are required for chromosome segregation. We isolated alleles of two genes involved in splicing, PRP16 and PRP19, which impair α-tubulin synthesis thus preventing spindle assembly, as well as an allele of CDC7 that is defective in DNA replication. We also report an initial characterization of phenotypes associated with the SMT3/SUMO gene and the isolation of WSS1, a high-copy smt3 suppressor.
The Yeast Recombinational Repair Protein Rad59 Interacts With Rad52 and Stimulates Single-Strand Annealing
Authors: Davis Allison P , Symington Lorraine S 
Published: April 2021

Abstract
The yeast RAD52 gene is essential for homology-dependent repair of DNA double-strand breaks. In vitro, Rad52 binds to single- and double-stranded DNA and promotes annealing of complementary single-stranded DNA. Genetic studies indicate that the Rad52 and Rad59 proteins act in the same recombination pathway either as a complex or through overlapping functions. Here we demonstrate physical interaction between Rad52 and Rad59 using the yeast two-hybrid system and co-immunoprecipitation from yeast extracts. Purified Rad59 efficiently anneals complementary oligonucleotides and is able to overcome the inhibition to annealing imposed by replication protein A (RPA). Although Rad59 has strand-annealing activity by itself in vitro, this activity is insufficient to promote strand annealing in vivo in the absence of Rad52. The rfa1-D288Y allele partially suppresses the in vivo strand-annealing defect of rad52 mutants, but this is independent of RAD59. These results suggest that in vivo Rad59 is unable to compete with RPA for single-stranded DNA and therefore is unable to promote single-strand annealing. Instead, Rad59 appears to augment the activity of Rad52 in strand annealing.
Molecular Population Genetics and Evolution of a Prion-like Protein in Saccharomyces cerevisiae
Authors: Jensen Mark A , True Heather L , Chernoff Yury O , Lindquist Susan 
Published: April 2021

Abstract
The prion-like behavior of Sup35p, the eRF3 homolog in the yeast Saccharomyces cerevisiae, mediates the activity of the cytoplasmic nonsense suppressor known as [PSI+]. Sup35p is divided into three regions of distinct function. The N-terminal and middle (M) regions are required for the induction and propagation of [PSI+] but are not necessary for translation termination or cell viability. The C-terminal region encompasses the termination function. The existence of the N-terminal region in SUP35 homologs of other fungi has led some to suggest that this region has an adaptive function separate from translation termination. To examine this hypothesis, we sequenced portions of SUP35 in 21 strains of S. cerevisiae, including 13 clinical isolates. We analyzed nucleotide polymorphism within this species and compared it to sequence divergence from a sister species, S. paradoxus. The N domain of Sup35p is highly conserved in amino acid sequence and is highly biased in codon usage toward preferred codons. Amino acid changes are under weak purifying selection based on a quantitative analysis of polymorphism and divergence. We also conclude that the clinical strains of S. cerevisiae are not recently derived and that outcrossing between strains in S. cerevisiae may be relatively rare in nature.
Epistatic and Synergistic Interactions Between Circadian Clock Mutations in Neurospora crassa
Authors: Morgan Louis W , Feldman Jerry F 
Published: April 2021

Abstract
We identified a series of epistatic and synergistic interactions among the circadian clock mutations of Neurospora crassa that indicate possible physical interactions among the various clock components encoded by these genes. The period-6 (prd-6) mutation, a short-period temperature-sensitive clock mutation, is epistatic to both the prd-2 and prd-3 mutations. The prd-2 and prd-3 long-period mutations show a synergistic interaction in that the period length of the double mutant strain is considerably longer than predicted. In addition, the prd-2 prd-3 double mutant strain also exhibits overcompensation to changes in ambient temperature, suggesting a role in the temperature compensation machinery of the clock. The prd-2, prd-3, and prd-6 mutations also show significant interactions with the frq7 long-period mutation. These results suggest that the gene products of prd-2, prd-3, and prd-6 play an important role in both the timing and temperature compensation mechanisms of the circadian clock and may interact with the FRQ protein.
Multiple Quantitative Trait Locus Analysis of Bovine Chromosome 6 in the Israeli Holstein Population by a Daughter Design
Authors: Ron Micha , Kliger David , Feldmesser Esther , Seroussi Eyal , Ezra Ephraim , Weller Joel Ira 
Published: April 2021

Abstract
Nine Israeli Holstein sire families with 2978 daughters were analyzed for quantitative trait loci effects on chromosome 6 for five milk production traits by a daughter design. All animals were genotyped for 2 markers. The three families with significant effects were genotyped for up to 10 additional markers spanning positions 0–122 cM of BTA6. Two sires were segregating for a locus affecting protein and fat percentage near position 55 cM with an estimated substitution effect of 0.18% protein, which is equivalent to one phenotypic standard deviation. This locus was localized to a confidence interval of 4 cM. One of these sires was also heterozygous for a locus affecting milk, fat, and protein production near the centromere. The hypothesis of two segregating loci was verified by multiple regression analysis. A third sire was heterozygous for a locus affecting milk and protein percentage near the telomeric end of the chromosome. Possible candidates for the major quantitative gene near position 55 cM were determined by comparative mapping. IBSP and SSP1 were used as anchors for the orthologous region on human chromosome 4. Twelve genes were detected within a 2-Mbp sequence. None of these genes have been previously associated with lactogenesis.
Synergistic Derepression of Gibberellin Signaling by Removing RGA and GAI Function in Arabidopsis thaliana
Authors: Dill Alyssa , Sun Tai-ping 
Published: April 2021

Abstract
RGA and GAI are negative regulators of the gibberellin (GA) signal transduction pathway in Arabidopsis thaliana. These genes may have partially redundant functions because they are highly homologous, and plants containing single null mutations at these loci are phenotypically similar to wild type. Previously, rga loss-of-function mutations were shown to partially suppress defects of the GA-deficient ga1-3 mutant. Phenotypes rescued include abaxial trichome initiation, rosette radius, flowering time, stem elongation, and apical dominance. Here we present work showing that the rga-24 and gai-t6 null mutations have a synergistic effect on plant growth. Although gai-t6 alone has little effect, when combined with rga-24, they completely rescued the above defects of ga1-3 to wild-type or GA-overdose phenotype. However, seed germination and flower development defects were not restored. Additionally, rga-24 and rga-24/gai-t6 but not gai-t6 alone caused increased feedback inhibition of expression of a GA biosynthetic gene in both the ga1-3 and wild-type backgrounds. These results demonstrate that RGA and GAI have partially redundant functions in maintaining the repressive state of the GA-signaling pathway, but RGA plays a more dominant role than GAI. Removing both RGA and GAI function allows for complete derepression of many aspects of GA signaling.
Intrahaplotype Polymorphism at the Brassica S Locus
Authors: Miege Christine , Ruffio-Châble Véronique , Schierup Mikkel H , Cabrillac Didier , Dumas Christian , Gaude Thierry , Cock J Mark 
Published: April 2021

Abstract
The S locus receptor kinase and the S locus glycoproteins are encoded by genes located at the S locus, which controls the self-incompatibility response in Brassica. In class II self-incompatibility haplotypes, S locus glycoproteins can be encoded by two different genes, SLGA and SLGB. In this study, we analyzed the sequences of these genes in several independently isolated plants, all of which carry the same S haplotype (S2). Two groups of S2 haplotypes could be distinguished depending on whether SRK was associated with SLGA or SLGB. Surprisingly, SRK alleles from the two groups could be distinguished at the sequence level, suggesting that recombination rarely occurs between haplotypes of the two groups. An analysis of the distribution of polymorphisms along the S domain of SRK showed that hypervariable domains I and II tend to be conserved within haplotypes but to be highly variable between haplotypes. This is consistent with these domains playing a role in the determination of haplotype specificity.
Drosophila-Raf Acts to Elaborate Dorsoventral Pattern in the Ectoderm of Developing Embryos
Authors: Radke Kori , Johnson Kimberly , Guo Rong , Davidson Anne , Ambrosio Linda 
Published: April 2021

Abstract
In the early Drosophila embryo the activity of the EGF-receptor (Egfr) is required to instruct cells to adopt a ventral neuroectodermal fate. Using a gain-of-function mutation we showed that D-raf acts to transmit this and other late-acting embryonic Egfr signals. A novel role for D-raf was also identified in lateral cell development using partial loss-of-function D-raf mutations. Thus, we provide evidence that zygotic D-raf acts to specify cell fates in two distinct pathways that generate dorsoventral pattern within the ectoderm. These functional requirements for D-raf activity occur subsequent to its maternal role in organizing the anterioposterior axis. The consequences of eliminating key D-raf regulatory domains and specific serine residues in the transmission of Egfr and lateral epidermal signals were also addressed here.
An Analysis of Polygenes Affecting Wing Shape on Chromosome 2 in Drosophila melanogaster
Authors: Weber Kenneth , Eisman Robert , Higgins Shawn , Morey Lisa , Patty April , Tausek Michele , Zeng Zhao-Bang 
Published: April 2021

Abstract
Genetic effects on an index of wing shape on chromosome 2 of Drosophila melanogaster were mapped using isogenic recombinants with transposable element markers. At least 10 genes with small additive effects are dispersed evenly along the chromosome. Many interactions exist, with only small net effects in homozygous recombinants and little effect on phenotypic variance. Heterozygous chromosome segments show almost no dominance. Pleiotropic effects on leg shape are only minor. At first view, wing shape genes form a rather homogeneous class, but certain complexities remain unresolved.
Expanding the Diversity of the IS630-Tc1-mariner Superfamily: Discovery of a Unique DD37E Transposon and Reclassification of the DD37D and DD39D Transposons
Authors: Shao Hongguang , Tu Zhijian 
Published: April 2021

Abstract
A novel transposon named ITmD37E was discovered in a wide range of mosquito species. Sequence analysis of multiple copies in three Aedes species showed similar terminal inverted repeats and common putative TA target site duplications. The ITmD37E transposases contain a conserved DD37E catalytic motif, which is unique among reported transposons of the IS630-Tc1-mariner superfamily. Sequence comparisons and phylogenetic analyses suggest that ITmD37E forms a novel family distinct from the widely distributed Tc1 (DD34E), mariner (DD34D), and pogo (DDxD) families in the IS630-Tc1-mariner superfamily. The inclusion in the phylogenetic analysis of recently reported transposons and transposons uncovered in our database survey provided revisions to previous classifications and identified two additional families, ITmD37D and ITmD39D, which contain DD37D and DD39D motifs, respectively. The above expansion and reorganization may open the doors to the discovery of related transposons in a broad range of organisms and help illustrate the evolution and structure-function relationships among these distinct transposases in the IS630-Tc1-mariner superfamily. The presence of intact open reading frames and highly similar copies in some of the newly characterized transposons suggests recent transposition. Studies of these novel families may add to the limited repertoire of transgenesis and mutagenesis tools for a wide range of organisms, including the medically important mosquitoes.
Female Meiosis Drives Karyotypic Evolution in Mammals
Authors: de Villena Fernando Pardo-Manuel , Sapienza Carmen 
Published: April 2021

Abstract
Speciation is often accompanied by changes in chromosomal number or form even though such changes significantly reduce the fertility of hybrid intermediates. We have addressed this evolutionary paradox by expanding the principle that nonrandom segregation of chromosomes takes place whenever human or mouse females are heterozygous carriers of Robertsonian translocations, a common form of chromosome rearrangement in mammals. Our analysis of 1170 mammalian karyotypes provides strong evidence that karyotypic evolution is driven by nonrandom segregation during female meiosis. The pertinent variable in this form of meiotic drive is the presence of differing numbers of centromeres on paired homologous chromosomes. This situation is encountered in all heterozygous carriers of Robertsonian translocations. Whenever paired chromosomes have different numbers of centromeres, the inherent asymmetry of female meiosis and the polarity of the meiotic spindle dictate that the partner with the greater number of centromeres will attach preferentially to the pole that is most efficient at capturing centromeres. This mechanism explains how chromosomal variants become fixed in populations, as well as why closely related species often appear to have evolved by directional adjustment of the karyotype toward or away from a particular chromosome form. If differences in the ability of particular DNA sequences or chromosomal regions to function as centromeres are also considered, nonrandom segregation is likely to affect karyotype evolution across a very broad phylogenetic range.
An Integrated Map of Arabidopsis thaliana for Functional Analysis of Its Genome Sequence
Authors: Chang Yueh-Long , Tao Quanzhou , Scheuring Chantel , Ding Kejiao , Meksem Khalid , Zhang Hong-Bin 
Published: April 2021

Abstract
The genome of the model plant species Arabidopsis thaliana has recently been sequenced. To accelerate its current genome research, we developed a whole-genome, BAC/BIBAC-based, integrated physical, genetic, and sequence map of the A. thaliana ecotype Columbia. This new map was constructed from the clones of a new plant-transformation-competent BIBAC library and is integrated with the existing sequence map. The clones were restriction fingerprinted by DNA sequencing gel-based electrophoresis, assembled into contigs, and anchored to an existing genetic map. The map consists of 194 BAC/BIBAC contigs, spanning 126 Mb of the 130-Mb Arabidopsis genome. A total of 120 contigs, spanning 114 Mb, were anchored to the chromosomes of Arabidopsis. Accuracy of the integrated map was verified using the existing physical and sequence maps and numerous DNA markers. Integration of the new map with the sequence map has enabled gap closure of the sequence map and will facilitate functional analysis of the genome sequence. The method used here has been demonstrated to be sufficient for whole-genome physical mapping from large-insert random bacterial clones and thus is applicable to rapid development of whole-genome physical maps for other species.
The Spo12 Protein of Saccharomyces cerevisiae: A Regulator of Mitotic Exit Whose Cell Cycle-Dependent Degradation Is Mediated by the Anaphase-Promoting Complex
Authors: Shah Rajvee , Jensen Sanne , Frenz Lisa M , Johnson Anthony L , Johnston Leland H 
Published: April 2021

Abstract
The Spo12 protein plays a regulatory role in two of the most fundamental processes of biology, mitosis and meiosis, and yet its biochemical function remains elusive. In this study we concentrate on the genetic and biochemical analysis of its mitotic function. Since high-copy SPO12 is able to suppress a wide variety of mitotic exit mutants, all of which arrest with high Clb-Cdc28 activity, we speculated whether SPO12 is able to facilitate exit from mitosis when overexpressed by antagonizing mitotic kinase activity. We show, however, that Spo12 is not a potent regulator of Clb-Cdc28 activity and can function independently of either the cyclin-dependent kinase inhibitor (CDKi), Sic1, or the anaphase-promoting complex (APC) regulator, Hct1. Spo12 protein level is regulated by the APC and the protein is degraded in G1 by an Hct1-dependent mechanism. We also demonstrate that in addition to localizing to the nucleus Spo12 is a nucleolar protein. We propose a model where overexpression of Spo12 may lead to the delocalization of a small amount of Cdc14 from the nucleolus, resulting in a sufficient lowering of mitotic kinase levels to facilitate mitotic exit. Finally, site-directed mutagenesis of highly conserved residues in the Spo12 protein sequence abolishes both its mitotic suppressor activity as well as its meiotic function. This result is the first indication that Spo12 may carry out the same biochemical function in mitosis as it does in meiosis.
Growth-Dependent DNA Breakage and Cell Death in a Gyrase Mutant of Salmonella
Authors: Garí Eloi , Bossi Lionello , Figueroa-Bossi Nara 
Published: April 2021

Abstract
A class of gyrase mutants of Salmonella enterica mimics the properties of bacteria exposed to quinolones. These mutants suffer spontaneous DNA breakage during normal growth and depend on recombinational repair for viability. Unlike quinolone-treated bacteria, however, they do not show accumulation of cleavable gyrase-DNA complexes. In recA or recB mutant backgrounds, the temperature-sensitive (ts) allele gyrA208 causes rapid cell death at 43°. Here, we isolated “suppressor-of-death” mutations, that is, secondary changes that allow a gyrA208 recB double mutant to survive a prolonged exposure to 43° and subsequently to form colonies at 28°. In most isolates, the secondary change was itself a ts mutation. Three ts alleles were mapped in genes coding for amino acyl tRNA synthetases (alaS, glnS, and lysS). Allele alaS216 completely abolished DNA breakage in a gyrA208 recA double mutant. Likewise, treating this mutant with chloramphenicol prevented death and DNA damage at 43°. Additional suppressors of gyrA208 lethality include rpoB mutations and, surprisingly, icd mutations inactivating isocitrate dehydrogenase. We postulate that the primary effect of the gyrase alteration is to hamper replication fork movement. Inhibiting DNA replication under conditions of continuing macromolecular synthesis (“unbalanced growth”) activates a mechanism that causes DNA breakage and cell death, reminiscent of “thymineless” lethality.