bluuebunny/crossref_metadata_2025_split huggingface dataset:
Functions of Fission Yeast Orp2 in DNA Replication and Checkpoint Control
Authors: Kiely Joan , Haase S B , Russell Paul , Leatherwood Janet 
Published: April 2021

Abstract
orp2 is an essential gene of the fission yeast Schizosaccharomyces pombe with 22% identity to budding yeast ORC2. We isolated temperature-sensitive alleles of orp2 using a novel plasmid shuffle based on selection against thymidine kinase. Cells bearing the temperature-sensitive allele orp2-2 fail to complete DNA replication at a restrictive temperature and undergo cell cycle arrest. Cell cycle arrest depends on the checkpoint genes rad1 and rad3. Even when checkpoint functions are wild type, the orp2-2 mutation causes high rates of chromosome and plasmid loss. These phenotypes support the idea that Orp2 is a replication initiation factor. Selective spore germination allowed analysis of orp2 deletion mutants. These experiments showed that in the absence of orp2 function, cells proceed into mitosis despite a lack of DNA replication. This suggests either that the Orp2 protein is a part of the checkpoint machinery or more likely that DNA replication initiation is required to induce the replication checkpoint signal.
Fixation of Advantageous Alleles in Partially Self-Fertilizing Populations: The Effect of Different Selection Modes
Authors: Damgaard Christian 
Published: April 2021

AbstractThe expected fixation probability of an advantageous allele was examined in a partially self-fertilizing hermaphroditic plant species using the diffusion approximation. The selective advantage of the advantageous allele was assumed to be increased viability, increased fecundity, or an increase in male fitness. The mode of selection, as well as the selfing rate, the population size, and the dominance of the advantageous allele, affect the fixation probability of the allele. In general it was found that increases in selfing rate decrease the fixation probability under male sexual selection, increase fixation probability under fecundity selection, and increase when recessive and decrease when dominant under viability selection. In some cases the highest fixation probability of advantageous alleles under fecundity or under male sexual selection occurred at an intermediary selfing rate. The expected mean fixation times of the advantageous allele were also examined using the diffusion approximation.
Comparative Sequence Analysis and Patterns of Covariation in RNA Secondary Structures
Authors: Parsch John , Braverman John M , Stephan Wolfgang 
Published: April 2021

Abstract
A novel method of RNA secondary structure prediction based on a comparison of nucleotide sequences is described. This method correctly predicts nearly all evolutionarily conserved secondary structures of five different RNAs: tRNA, 5S rRNA, bacterial ribonuclease P (RNase P) RNA, eukaryotic small subunit rRNA, and the 3′ untranslated region (UTR) of the Drosophila bicoid (bcd) mRNA. Furthermore, covariations occurring in the helices of these conserved RNA structures are analyzed. Two physical parameters are found to be important determinants of the evolution of compensatory mutations: the length of a helix and the distance between base-pairing nucleotides. For the helices of bcd 3′ UTR mRNA and RNase P RNA, a positive correlation between the rate of compensatory evolution and helix length is found. The analysis of Drosophila bcd 3′ UTR mRNA further revealed that the rate of compensatory evolution decreases with the physical distance between base-pairing residues. This result is in qualitative agreement with Kimura's model of compensatory fitness interactions, which assumes that mutations occurring in RNA helices are individually deleterious but become neutral in appropriate combinations.
Three Subfamilies of Pheromone and Receptor Genes Generate Multiple B Mating Specificities in the Mushroom Coprinus cinereus
Authors: Halsall John R , Milner Michael J , Casselton Lorna A 
Published: April 2021

Abstract
The B mating type locus of the basidiomycete Coprinus cinereus encodes a large family of lipopeptide pheromones and their seven transmembrane domain receptors. Here we show that the B42 locus, like the previously described B6 locus, derives its unique specificity from nine multiallelic genes that are organized into three subgroups each comprising a receptor and two pheromone genes. We show that the three genes within each group are kept together as a functional unit by being embedded in an allele-specific DNA sequence. Using a combination of sequence analysis, Southern blotting, and DNA-mediated transformation with cloned genes, we demonstrate that different B loci may share alleles of one or two groups of genes. This is consistent with the prediction that the three subgroups of genes are functionally redundant and that it is the different combinations of their alleles that generate the multiple B mating specificities found in nature. The B42 locus was found to contain an additional gene, mfs1, that encodes a putative multidrug transporter belonging to the major facilitator family. In strains with other B mating specificities, this gene, whose functional significance was not established, lies in a region of shared homology flanking the B locus.
Balancing Selection at Closely Linked, Overdominant Loci in a Finite Population
Authors: Slatkin Montgomery 
Published: April 2021

AbstractHigh levels of allelic diversity and strong linkage disequilibrium are found in the major histocompatibility (MHC) system in humans and other vertebrates. This article proposes several descriptive statistics that quantify the extent and pattern of strong linkage disequilibrium between pairs of highly polymorphic loci. It also develops an approximate analytic theory incorporating the effects of balancing selection, mutation, recombination, and genetic drift at two closely linked loci and compares the theoretical predictions with published surveys of the MHC class II loci, DQA1 and DQB1, in humans and nonhuman primates. The descriptive statistics proposed include the fraction of complementary haplotypes (haplotypes with D″ = 1), the fraction of excess haplotypes, and the numbers of alleles at each locus in complementary haplotypes with one or more alleles at the other locus. The model assumes the infinite alleles model of mutation and the symmetric overdominance model of selection. Analytic approximations in some cases are obtained in the strong selection, weak mutation (SSWM) limit introduced by J. Gillespie. The predictions of the approximate analysis are confirmed by simulation. Both the analytic theory and simulations show that relatively few haplotypes will be found when selection is strong and recombination is weak relative to genetic drift. The model can reproduce many of the observed patterns at DQA1 and DQB1 provided that the recombination rate is assumed to be very small.
Regulation of the Yeast INO1 Gene: The Products of the INO2, INO4 and OPI1 Regulatory Genes Are Not Required for Repression in Response to Inositol
Authors: Graves J Anthony , Henry Susan A 
Published: April 2021

Abstract
The ino2Δ, ino4Δ, opi1Δ, and sin3Δ mutations all affect expression of INO1, a structural gene for inositol-1-phosphate synthase. These same mutations affect other genes of phospholipid biosynthesis that, like INO1, contain the repeated element UASINO (consensus 5′ CATGTGAAAT 3′). In this study, we evaluated the effects of these four mutations, singly and in all possible combinations, on growth and expression of INO1. All strains carrying an ino2Δ or ino4Δ mutation, or both, failed to grow in medium lacking inositol. However, when grown in liquid culture in medium containing limiting amounts of inositol, the opi1Δ ino4Δ strain exhibited a level of INO1 expression comparable to, or higher than, the wild-type strain growing under the same conditions. Furthermore, INO1 expression in the opi1Δ ino4Δ strain was repressed in cells grown in medium fully supplemented with both inositol and choline. Similar results were obtained using the opi1Δ ino2Δ ino4Δ strain. Regulation of INO1 was also observed in the absence of the SIN3 gene product. Therefore, while Opi1p, Sin3p, and the Ino2p/Ino4p complex all affect the overall level of INO1 expression in an antagonistic manner, they do not appear to be responsible for transmitting the signal that leads to repression of INO1 in response to inositol. Various models for Opi1p function were tested and no evidence for binding of Opi1p to UASINO, or to Ino2p or Ino4p, was obtained.
The Origin of the Domestic Pig: Independent Domestication and Subsequent Introgression
Authors: Giuffra E , Kijas J M H , Amarger V , Carlborg Ö , Jeon J-T , Andersson L 
Published: April 2021

Abstract
The domestic pig originates from the Eurasian wild boar (Sus scrofa). We have sequenced mitochondrial DNA and nuclear genes from wild and domestic pigs from Asia and Europe. Clear evidence was obtained for domestication to have occurred independently from wild boar subspecies in Europe and Asia. The time since divergence of the ancestral forms was estimated at ~500,000 years, well before domestication ~9,000 years ago. Historical records indicate that Asian pigs were introduced into Europe during the 18th and early 19th centuries. We found molecular evidence for this introgression and the data indicated a hybrid origin of some major “European” pig breeds. The study is an advance in pig genetics and has important implications for the maintenance and utilization of genetic diversity in this livestock species.
Predicting Rates of Inbreeding in Populations Undergoing Selection
Authors: Woolliams John A , Bijma Piter 
Published: April 2021

Abstract
Tractable forms of predicting rates of inbreeding (ΔF) in selected populations with general indices, nonrandom mating, and overlapping generations were developed, with the principal results assuming a period of equilibrium in the selection process. An existing theorem concerning the relationship between squared long-term genetic contributions and rates of inbreeding was extended to nonrandom mating and to overlapping generations. ΔF was shown to be ~¼(1 − ω) times the expected sum of squared lifetime contributions, where ω is the deviation from Hardy-Weinberg proportions. This relationship cannot be used for prediction since it is based upon observed quantities. Therefore, the relationship was further developed to express ΔF in terms of expected long-term contributions that are conditional on a set of selective advantages that relate the selection processes in two consecutive generations and are predictable quantities. With random mating, if selected family sizes are assumed to be independent Poisson variables then the expected long-term contribution could be substituted for the observed, providing ¼ (since ω = 0) was increased to ½. Established theory was used to provide a correction term to account for deviations from the Poisson assumptions. The equations were successfully applied, using simple linear models, to the problem of predicting ΔF with sib indices in discrete generations since previously published solutions had proved complex.
Molecular Evolution of Odorant-Binding Protein Genes OS-E and OS-F in Drosophila
Authors: Hekmat-Scafe Daria S , Dorit Robert L , Carlson John R 
Published: April 2021

Abstract
The Drosophila olfactory genes OS-E and OS-F are members of a family of genes that encode insect odorant-binding proteins (OBPs). OBPs are believed to transport hydrophobic odorants through the aqueous fluid within olfactory sensilla to the underlying receptor proteins. The recent discovery of a large family of olfactory receptor genes in Drosophila raises new questions about the function, diversity, regulation, and evolution of the OBP family. We have investigated the OS-E and OS-F genes in a variety of Drosophila species. These studies highlight potential regions of functional significance in the OS-E and OS-F proteins, which may include a region required for interaction with receptor proteins. Our results suggest that the two genes arose by an ancient gene duplication, and that in some lineages, one or the other gene has been lost. In D. virilis, the OS-F gene shows a different spatial pattern of expression than in D. melanogaster. One of the OS-F introns shows a striking degree of conservation between the two species, and we identify a putative regulatory sequence within this intron. Finally, a phylogenetic analysis places both OS-E and OS-F within a large family of insect OBPs and OBP-like proteins.
Genetic Analysis of the Hybrid male rescue Locus of Drosophila
Authors: Orr H Allen , Irving Shannon 
Published: April 2021

Abstract
Several hybrid rescue mutations—alleles that restore the viability of normally lethal hybrids—have been discovered in Drosophila melanogaster and its relatives. Here we analyze one of these genes, Hybrid male rescue (Hmr), asking two questions about its role in hybrid inviability. (1) Does the wild-type allele from D. melanogaster (Hmrmel) cause hybrid embryonic inviability? (2) Does Hmrmel cause hybrid larval inviability? Our results show that the wild-type product of Hmr is neither necessary nor sufficient for hybrid embryonic inviability. Hmrmel does, however, appear to lower the viability of hybrid larvae. The data further suggest (though do not prove) that Hmrmel acts as a gain-of-function poison in hybrids. These findings support previous claims that hybrid embryonic and larval lethalities are genetically distinct and suggest that Hmrmel is at least one of the proximate causes of hybrid larval inviability.
Heritability of the Maternal Meiotic Drive System Linked toOmand High-Resolution Mapping of theResponderLocus in Mouse
Authors: de Villena Fernando Pardo-Manuel , de la Casa-Esperón Elena , Williams Jean W , Malette Jan-Michel , Rosa Michelle , Sapienza Carmen 
Published: April 2021

AbstractABSTRACT Matings between (C57BL/6 × DDK)F1 females and C57BL/6 males result in a significant excess of offspring inheriting maternal DDK alleles in the central region of mouse chromosome 11 due to meiotic drive at the second meiotic division. We have shown previously that the locus subject to selection is in the vicinity of D11Mit66, a marker closely linked to the Om locus that controls the preimplantation embryolethal phenotype known as the “DDK syndrome.” We have also shown that observation of meiotic drive in this system depends upon the genotype of the sire. Here we show that females that are heterozygous at Om retain the meiotic drive phenotype and define a 0.32-cM candidate interval for the Responder locus in this drive system. In addition, analysis of the inheritance of alleles at Om among the offspring of F1 intercrosses indicates that the effect of the sire is determined by the sperm genotype at Om or a locus linked to Om.
Codon-Substitution Models for Heterogeneous Selection Pressure at Amino Acid Sites
Authors: Yang Ziheng , Nielsen Rasmus , Goldman Nick , Pedersen Anne-Mette Krabbe 
Published: April 2021

Abstract
Comparison of relative fixation rates of synonymous (silent) and nonsynonymous (amino acid-altering) mutations provides a means for understanding the mechanisms of molecular sequence evolution. The nonsynonymous/synonymous rate ratio (ω = dN/dS) is an important indicator of selective pressure at the protein level, with ω = 1 meaning neutral mutations, ω &lt; 1 purifying selection, and ω &gt; 1 diversifying positive selection. Amino acid sites in a protein are expected to be under different selective pressures and have different underlying ω ratios. We develop models that account for heterogeneous ω ratios among amino acid sites and apply them to phylogenetic analyses of protein-coding DNA sequences. These models are useful for testing for adaptive molecular evolution and identifying amino acid sites under diversifying selection. Ten data sets of genes from nuclear, mitochondrial, and viral genomes are analyzed to estimate the distributions of ω among sites. In all data sets analyzed, the selective pressure indicated by the ω ratio is found to be highly heterogeneous among sites. Previously unsuspected Darwinian selection is detected in several genes in which the average ω ratio across sites is &lt;1, but in which some sites are clearly under diversifying selection with ω &gt; 1. Genes undergoing positive selection include the β-globin gene from vertebrates, mitochondrial protein-coding genes from hominoids, the hemagglutinin (HA) gene from human influenza virus A, and HIV-1 env, vif, and pol genes. Tests for the presence of positively selected sites and their subsequent identification appear quite robust to the specific distributional form assumed for ω and can be achieved using any of several models we implement. However, we encountered difficulties in estimating the precise distribution of ω among sites from real data sets.
Conidial Germination in Aspergillus nidulans Requires RAS Signaling and Protein Synthesis
Authors: Osherov Nir , May Gregory 
Published: April 2021

Abstract
The dormant spores of Aspergillus nidulans become competent for growth and nuclear division in a process called conidial germination. To analyze the molecular details of conidial germination, we developed a genetic screen in which we identified spore germination-deficient mutants that are blocked in this process at the restrictive temperature. These mutants defined eight genes, of which we identified five. Four of the five were directly involved in translation and protein folding, and the fifth showed a high degree of homology to a malonyl CoA synthetase. These results suggest that out of a wide array of processes occurring during conidial germination, translation is essential if germination is to proceed. We also show that conidia containing a mutant-activated form of rasA, the ras homologue in A. nidulans, germinate in the absence of an inducing carbon source, suggesting an important role for rasA signaling in conidial germination. Together these data suggest a model by which a carbon source activates a ras-dependent sensory mechanism, inducing translation and leading to conidial germination. This study shows that conidial germination in A. nidulans requires protein synthesis and that the initiation of translation is linked, through an as yet to be determined signaling cascade that includes rasA, to a carbon-source-sensing apparatus.
Analysis of maxillopedia Expression Pattern and Larval Cuticular Phenotype in Wild-Type and Mutant Tribolium
Authors: Shippy Teresa D , Guo Jianhua , Brown Susan J , Beeman Richard W , Denell Robin E 
Published: April 2021

Abstract
The Tribolium castaneum homeotic gene maxillopedia (mxp) is the ortholog of Drosophila proboscipedia (pb). Here we describe and classify available mxp alleles. Larvae lacking all mxp function die soon after hatching, exhibiting strong transformations of maxillary and labial palps to legs. Hypomorphic mxp alleles produce less severe transformations to leg. RNA interference with maxillopedia double-stranded RNA results in phenocopies of mxp mutant phenotypes ranging from partial to complete transformations. A number of gain-of-function (GOF) mxp alleles have been isolated based on transformations of adult antennae and/or legs toward palps. Finally, we have characterized the mxp expression pattern in wild-type and mutant embryos. In normal embryos, mxp is expressed in the maxillary and labial segments, whereas ectopic expression is observed in some GOF variants. Although mxp and Pb display very similar expression patterns, pb null embryos develop normally. The mxp mutant larval phenotype in Tribolium is consistent with the hypothesis that an ancestral pb-like gene had an embryonic function that was lost in the lineage leading to Drosophila.
Physical Mapping of Male Fertility and Meiotic Drive Quantitative Trait Loci in the Mouse t Complex Using Chromosome Deficiencies
Authors: Planchart Antonio , You Yun , Schimenti John C 
Published: April 2021

Abstract
The t complex spans 20 cM of the proximal region of mouse chromosome 17. A variant form, the t haplotype (t), exists at significant frequencies in wild mouse populations and is characterized by the presence of inversions that suppress recombination with wild-type (+) chromosomes. Transmission ratio distortion and sterility are associated with t and affect males only. It is hypothesized that these phenomena are caused by trans-acting distorter/sterility factors that interact with a responder locus (Tcrt) and that the distorter and sterility factors are the same because homozygosity of the distorters causes male sterility. One factor, Tcd1, was previously shown to be amorphic using a chromosome deletion. To overcome limitations imposed by recombination suppression, we used a series of deletions within the t complex in trans to t chromosomes to characterize the Tcd1 region. We find that the distorter activity of Tcd1 is distinct from a linked sterility factor, originally called tcs1. YACs mapped with respect to deletion breakpoints localize tcs1 to a 1.1-Mb interval flanked by D17Aus9 and Tctex1. We present evidence for the existence of multiple proximal t complex regions that exhibit distorter activity. These studies demonstrate the utility of chromosome deletions for complex trait analysis.
The Effects of Pollen and Seed Migration on Nuclear-Dicytoplasmic Systems. I. Nonrandom Associations and Equilibrium Structure With Both Maternal and Paternal Cytoplasmic Inheritance
Authors: Asmussen Marjorie A , Orive Maria E 
Published: April 2021

Abstract
We determine the nuclear-dicytoplasmic effects of unidirectional gene flow via pollen and seeds upon a mixed-mating plant population, focusing on nuclear-mitochondrial-chloroplast systems where mitochondria are inherited maternally and chloroplasts paternally, as in many conifers. After first delineating the general effects of admixture (via seeds or individuals) on the nonrandom associations in such systems, we derive the full dicytonuclear equilibrium structure, including when disequilibria may be indicators of gene flow. Substantial levels of permanent two- and three-locus disequilibria can be generated in adults by (i) nonzero disequilibria in the migrant pools or (ii) intermigrant admixture effects via different chloroplast frequencies in migrant pollen and seeds. Additionally, three-locus disequilibria can be generated by higher-order intermigrant effects such as different chloroplast frequencies in migrant pollen and seeds coupled with nuclear-mitochondrial disequilibria in migrant seeds, or different nuclear frequencies in migrant pollen and seeds coupled with mitochondrial-chloroplast disequilibria in migrant seeds. Further insight is provided by considering special cases with seed or pollen migration alone, complete random mating or selfing, or migrant pollen and seeds lacking disequilibria or intermigrant admixture effects. The results complete the theoretical foundation for a new method for estimating pollen and seed migration using joint cytonuclear or dicytonuclear data.