bluuebunny/crossref_metadata_2025_split huggingface dataset:
Spectrum of Nonrandom Associations Between Microsatellite Loci on Human Chromosome 11p15
Authors: Zapata Carlos , Rodríguez Santiago , Visedo Guillermo , Sacristán Felipe 
Published: April 2021

AbstractMost evidence about nonrandom association of alleles at different loci, or gametic disequilibrium, across extensive anonymous regions of the human genome is based on the analysis of overall disequilibrium between pairs of microsatellites. However, analysis of interallelic associations is also necessary for a more complete description of disequilibrium. Here, we report a study characterizing the frequency and strength of both overall and interallelic disequilibrium between pairs of 12 microsatellite loci (CA repeats) spanning 19 cM (14 Mb) on human chromosome 11p15, in a large sample (810 haplotypes deduced from 405 individuals) drawn from a single population. Characterization of disequilibrium was carried out, taking into account the sign of the observed disequilibria. This strategy facilitates detection of associations and gives more accurate estimates of their intensities. Our results demonstrate that the incidence of disequilibrium over an extensive human chromosomal region is much greater than is commonly considered for populations that have expanded in size. In total, 44% of the pairs of microsatellite loci and 18% of the pairs of alleles showed significant nonrandom association. All the loci were involved in disequilibrium, although both the frequency and strength of interallelic disequilibrium were distributed nonuniformly along 11p15. These findings are especially relevant since significant associations were detected between loci separated by as much as 17–19 cM (7 cM on average). It was also found that the overall disequilibrium masks complicated patterns of association between pairs of alleles, dependent on their frequency and size. We suggest that the complex mutational dynamics at microsatellite loci could explain the allele-dependent disequilibrium patterns. These observations are also relevant to evaluation of the usefulness of microsatellite markers for fine-scale localization of disease genes.
Multiple Losses and Transfers to the Nucleus of Two Mitochondrial Succinate Dehydrogenase Genes During Angiosperm Evolution
Authors: Adams Keith L , Rosenblueth Monica , Qiu Yin-Long , Palmer Jeffrey D 
Published: April 2021

Abstract
Unlike in animals, the functional transfer of mitochondrial genes to the nucleus is an ongoing process in plants. All but one of the previously reported transfers in angiosperms involve ribosomal protein genes. Here we report frequent transfer of two respiratory genes, sdh3 and sdh4 (encoding subunits 3 and 4 of succinate dehydrogenase), and we also show that these genes are present and expressed in the mitochondria of diverse angiosperms. Southern hybridization surveys reveal that sdh3 and sdh4 have been lost from the mitochondrion about 40 and 19 times, respectively, among the 280 angiosperm genera examined. Transferred, functional copies of sdh3 and sdh4 were characterized from the nucleus in four and three angiosperm families, respectively. The mitochondrial targeting presequences of two sdh3 genes are derived from preexisting genes for anciently transferred mitochondrial proteins. On the basis of the unique presequences of the nuclear genes and the recent mitochondrial gene losses, we infer that each of the seven nuclear sdh3 and sdh4 genes was derived from a separate transfer to the nucleus. These results strengthen the hypothesis that angiosperms are experiencing a recent evolutionary surge of mitochondrial gene transfer to the nucleus and reveal that this surge includes certain respiratory genes in addition to ribosomal protein genes.
Functional Divergence in the Caspase Gene Family and Altered Functional Constraints: Statistical Analysis and Prediction
Authors: Wang Yufeng , Gu Xun 
Published: April 2021

AbstractIn this article, we explore the pattern of type I functional divergence (i.e., altered functional constraints or site-specific rate difference) in the caspase gene family that is important for apoptosis (programmed cell death) and cytokine maturation. By taking advantage of substantial experimental data from caspases, the functional/structural basis of our posterior predictions from sequence analysis was extensively studied. Our results are as follows: (1) Phylogenetic analysis shows that the evolution of major caspase-mediated pathways has been facilitated by gene duplications, (2) type I functional divergence (altered functional constraints) is statistically significant between two major subfamilies, CED-3 and ICE, (3) 4 of 21 predicted amino acid residues (for site-specific rate difference between CED-3 and ICE) have been verified by experimental evidence, and (4) we found that some CED-3 caspases may inherit more ancestral functions, whereas other members may employ some recently derived functions. Our approach can be cost effective in functional genomics to make statistically sound predictions from amino acid sequences.
Disparity Index: A Simple Statistic to Measure and Test the Homogeneity of Substitution Patterns Between Molecular Sequences
Authors: Kumar Sudhir , Gadagkar Sudhindra R 
Published: April 2021

AbstractA common assumption in comparative sequence analysis is that the sequences have evolved with the same pattern of nucleotide substitution (homogeneity of the evolutionary process). Violation of this assumption is known to adversely impact the accuracy of phylogenetic inference and tests of evolutionary hypotheses. Here we propose a disparity index, ID, which measures the observed difference in evolutionary patterns for a pair of sequences. On the basis of this index, we have developed a Monte Carlo procedure to test the homogeneity of the observed patterns. This test does not require a priori knowledge of the pattern of substitutions, extent of rate heterogeneity among sites, or the evolutionary relationship among sequences. Computer simulations show that the ID-test is more powerful than the commonly used χ2-test under a variety of biologically realistic models of sequence evolution. An application of this test in an analysis of 3789 pairs of orthologous human and mouse protein-coding genes reveals that the observed evolutionary patterns in neutral sites are not homogeneous in 41% of the genes, apparently due to shifts in G + C content. Thus, the proposed test can be used as a diagnostic tool to identify genes and lineages that have evolved with substantially different evolutionary processes as reflected in the observed patterns of change. Identification of such genes and lineages is an important early step in comparative genomics and molecular phylogenetic studies to discover evolutionary processes that have shaped organismal genomes.
Excess of Rare Amino Acid Polymorphisms in the Toll-like Receptor 4 in Humans
Authors: Smirnova Irina , Hamblin Martha T , McBride Colleen , Beutler Bruce , Di Rienzo Anna 
Published: April 2021

AbstractThe Toll-like receptor 4 protein acts as the transducing subunit of the lipopolysaccharide receptor complex and assists in the detection of Gram-negative pathogens within the mammalian host. Several lines of evidence support the view that variation at the TLR4 locus may alter host susceptibility to Gram-negative infection or the outcome of infection. Here, we surveyed TLR4 sequence variation in the complete coding region (2.4 kb) in 348 individuals from several population samples; in addition, a subset of the individuals was surveyed at 1.1 kb of intronic sequence. More than 90% of the chromosomes examined encoded the same structural isoform of TLR4, while the rest harbored 12 rare amino acid variants. Conversely, the variants at silent sites (intronic and synonymous positions) occur at both low and high frequencies and are consistent with a neutral model of mutation and random drift. The spectrum of allele frequencies for amino acid variants shows a significant skew toward lower frequencies relative to both the neutral model and the pattern observed at linked silent sites. This is consistent with the hypothesis that weak purifying selection acted on TLR4 and that most mutations affecting TLR4 protein structure have at least mildly deleterious phenotypic effects. These results may imply that genetic variants contributing to disease susceptibility occur at low frequencies in the population and suggest strategies for optimizing the design of disease-mapping studies.
Overdominant Epistatic Loci Are the Primary Genetic Basis of Inbreeding Depression and Heterosis in Rice. I. Biomass and Grain Yield
Authors: Li Zhi-Kang , Luo L J , Mei H W , Wang D L , Shu Q Y , Tabien R , Zhong D B , Ying C S , Stansel J W , Khush G S , Paterson A H 
Published: April 2021

AbstractTo understand the genetic basis of inbreeding depression and heterosis in rice, main-effect and epistatic QTL associated with inbreeding depression and heterosis for grain yield and biomass in five related rice mapping populations were investigated using a complete RFLP linkage map of 182 markers, replicated phenotyping experiments, and the mixed model approach. The mapping populations included 254 F10 recombinant inbred lines derived from a cross between Lemont (japonica) and Teqing (indica) and two BC and two testcross hybrid populations derived from crosses between the RILs and their parents plus two testers (Zhong 413 and IR64). For both BY and GY, there was significant inbreeding depression detected in the RI population and a high level of heterosis in each of the BC and testcross hybrid populations. The mean performance of the BC or testcross hybrids was largely determined by their heterosis measurements. The hybrid breakdown (part of inbreeding depression) values of individual RILs were negatively associated with the heterosis measurements of their BC or testcross hybrids, indicating the partial genetic overlap of genes causing hybrid breakdown and heterosis in rice. A large number of epistatic QTL pairs and a few main-effect QTL were identified, which were responsible for &gt;65% of the phenotypic variation of BY and GY in each of the populations with the former explaining a much greater portion of the variation. Two conclusions concerning the loci associated with inbreeding depression and heterosis in rice were reached from our results. First, most QTL associated with inbreeding depression and heterosis in rice appeared to be involved in epistasis. Second, most (~90%) QTL contributing to heterosis appeared to be overdominant. These observations tend to implicate epistasis and overdominance, rather than dominance, as the major genetic basis of heterosis in rice. The implications of our results in rice evolution and improvement are discussed.
Genetic Control of Horizontal Virus Transmission in the Chestnut Blight Fungus,Cryphonectria parasitica
Authors: Cortesi Paolo , McCulloch Charles E , Song Haiyue , Lin Haiqun , Milgroom Michael G 
Published: April 2021

AbstractVegetative incompatibility in fungi has long been known to reduce the transmission of viruses between individuals, but the barrier to transmission is incomplete. In replicated laboratory assays, we showed conclusively that the transmission of viruses between individuals of the chestnut blight fungus Cryphonectria parasitica is controlled primarily by vegetative incompatibility (vic) genes. By replicating vic genotypes in independent fungal isolates, we quantified the effect of heteroallelism at each of six vic loci on virus transmission. Transmission occurs with 100% frequency when donor and recipient isolates have the same vic genotypes, but heteroallelism at one or more vic loci generally reduces virus transmission. Transmission was variable among single heteroallelic loci. At the extremes, heteroallelism at vic4 had no effect on virus transmission, but transmission occurred in only 21% of pairings that were heteroallelic at vic2. Intermediate frequencies of transmission were observed when vic3 and vic6 were heteroallelic (76 and 32%, respectively). When vic1, vic2, and vic7 were heteroallelic, the frequency of transmission depended on which alleles were present in the donor and the recipient. The effect of heteroallelism at two vic loci was mostly additive, although small but statistically significant interactions (epistasis) were observed in four pairs of vic loci. A logistic regression model was developed to predict the probability of virus transmission between vic genotypes. Heteroallelism at vic loci, asymmetry, and epistasis were the dominant factors controlling transmission, but host genetic background also was statistically significant, indicating that vic genes alone cannot explain all the variation in virus transmission. Predictions from the logistic regression model were highly correlated to independent transmission tests with field isolates. Our model can be used to estimate horizontal transmission rates as a function of host genetics in natural populations of C. parasitica.
Small, Repetitive DNAs Contribute Significantly to the Expanded Mitochondrial Genome of Cucumber
Authors: Lilly Jason W , Havey Michael J 
Published: April 2021

Abstract
Closely related cucurbit species possess eightfold differences in the sizes of their mitochondrial genomes. We cloned mitochondrial DNA (mtDNA) fragments showing strong hybridization signals to cucumber mtDNA and little or no signal to watermelon mtDNA. The cucumber mtDNA clones carried short (30–53 bp), repetitive DNA motifs that were often degenerate, overlapping, and showed no homology to any sequences currently in the databases. On the basis of dot-blot hybridizations, seven repetitive DNA motifs accounted for &gt;13% (194 kb) of the cucumber mitochondrial genome, equaling &gt;50% of the size of the Arabidopsis mitochondrial genome. Sequence analysis of 136 kb of cucumber mtDNA revealed only 11.2% with significant homology to previously characterized mitochondrial sequences, 2.4% to chloroplast DNA, and 15% to the seven repetitive DNA motifs. The remaining 71.4% of the sequence was unique to the cucumber mitochondrial genome. There was &lt;4% sequence colinearity surrounding the watermelon and cucumber atp9 coding regions, and the much smaller watermelon mitochondrial genome possessed no significant amounts of cucumber repetitive DNAs. Our results demonstrate that the expanded cucumber mitochondrial genome is in part due to extensive duplication of short repetitive sequences, possibly by recombination and/or replication slippage.
Spontaneous Frameshift Mutations in Saccharomyces cerevisiae: Accumulation During DNA Replication and Removal by Proofreading and Mismatch Repair Activities
Authors: Greene Christopher N , Jinks-Robertson Sue 
Published: April 2021

Abstract
The accumulation of frameshift mutations during DNA synthesis is determined by the rate at which frameshift intermediates are generated during DNA polymerization and the efficiency with which frameshift intermediates are removed by DNA polymerase-associated exonucleolytic proofreading activity and/or the postreplicative mismatch repair machinery. To examine the relative contributions of these factors to replication fidelity in Saccharomyces cerevisiae, we determined the reversion rates and spectra of the lys2ΔBgl +1 frameshift allele. Wild-type and homozygous mutant diploid strains with all possible combinations of defects in the exonuclease activities of DNA polymerases δ and ε (conferred by the pol3-01 and pol2-4 alleles, respectively) and in mismatch repair (deletion of MSH2) were analyzed. Although there was no direct correlation between homopolymer run length and frameshift accumulation in the wild-type strain, such a correlation was evident in the triple mutant strain lacking all repair capacity. Furthermore, examination of strains defective in one or two repair activities revealed distinct biases in the removal of the corresponding frameshift intermediates by exonucleolytic proofreading and/or mismatch repair. Finally, these analyses suggest that the mismatch repair machinery may be important for generating some classes of frameshift mutations in yeast.
Analysis of Corkscrew Signaling in the Drosophila Epidermal Growth Factor Receptor Pathway During Myogenesis
Authors: Hamlet Michelle R Johnson , Perkins Lizabeth A 
Published: April 2021

Abstract
The Drosophila nonreceptor protein tyrosine phosphatase, Corkscrew (Csw), functions positively in multiple receptor tyrosine kinase (RTK) pathways, including signaling by the epidermal growth factor receptor (EGFR). Detailed phenotypic analyses of csw mutations have revealed that Csw activity is required in many of the same developmental processes that require EGFR function. However, it is still unclear where in the signaling hierarchy Csw functions relative to other proteins whose activities are also required downstream of the receptor. To address this issue, genetic interaction experiments were performed to place csw gene activity relative to the EGFR, spitz (spi), rhomboid (rho), daughter of sevenless (DOS), kinase-suppressor of ras (ksr), ras1, D-raf, pointed (pnt), and moleskin. We followed the EGFR-dependent formation of VA2 muscle precursor cells as a sensitive assay for these genetic interaction studies. First, we established that Csw has a positive function during mesoderm development. Second, we found that tissue-specific expression of a gain-of-function csw construct rescues loss-of-function mutations in other positive signaling genes upstream of rolled (rl)/MAPK in the EGFR pathway. Third, we were able to infer levels of EGFR signaling in various mutant backgrounds during myogenesis. This work extends previous studies of Csw during Torso and Sevenless RTK signaling to include an in-depth analysis of the role of Csw in the EGFR signaling pathway.
Inbreeding Depression in Small Populations of Self-Incompatible Plants
Authors: Glémin Sylvain , Bataillon Thomas , Ronfort Joëlle , Mignot Agnès , Olivieri Isabelle 
Published: April 2021

Abstract
Self-incompatibility (SI) is a widespread mechanism that prevents inbreeding in flowering plants. In many species, SI is controlled by a single locus (the S locus) where numerous alleles are maintained by negative frequency-dependent selection. Inbreeding depression, the decline in fitness of selfed individuals compared to outcrossed ones, is an essential factor in the evolution of SI systems. Conversely, breeding systems influence levels of inbreeding depression. Little is known about the joint effect of SI and drift on inbreeding depression. Here we studied, using a two-locus model, the effect of SI (frequency-dependent selection) on a locus subject to recurrent deleterious mutations causing inbreeding depression. Simulations were performed to assess the effect of population size and linkage between the two loci on the level of inbreeding depression and genetic load. We show that the sheltering of deleterious alleles linked to the S locus strengthens inbreeding depression in small populations. We discuss the implications of our results for the evolution of SI systems.
A Chromosomal Region Promoting Outcrossing in a Conifer
Authors: Williams Claire G , Zhou Yi , Hall Sarah E 
Published: April 2021

AbstractPrefertilization mechanisms influencing selfing rates are thought to be absent in conifers. Outcrossing in conifers is promoted via an embryo-lethal system, but the genetic mechanism is poorly understood. This study is the first experimental profile of the genetic mechanism promoting outcrossing in conifers. Molecular dissection of a Pinus taeda L. selfed pedigree detected a chromosomal region identified as PtTX3020-RPtest9. Within this region, a semilethal factor was tightly linked (r = 0.0076) to a polymorphic expressed sequence tag (EST). The linkage group flanking the lethal factor showed strong heterozygote advantage. Using genotypic frequencies for the linkage group, three hypotheses about the semilethal factor could be tested: (1) the presence of a balanced lethal system, i.e., a lethal factor present in each of the two marker intervals; (2) gametic selection operative prior to fertilization; and (3) a stage-specific lethal factor. Selection acted via the embryo-lethal system. No support for a genetic mechanism operating prior to fertilization was found. The semilethal factor exerted no effect after embryo maturity. The genetic mechanism promoting outcrossing in P. taeda L. appears to have a balancing selection system due to either pseudo-overdominance or true overdominance.
Population Admixture May Appear to Mask, Change or Reverse Genetic Effects of Genes Underlying Complex Traits
Authors: Deng Hong-Wen 
Published: April 2021

Abstract
Association studies using random population samples are increasingly being applied in the identification and inference of genetic effects of genes underlying complex traits. It is well recognized that population admixture may yield false-positive identification of genetic effects for complex traits. However, it is less well appreciated that population admixture can appear to mask, change, or reverse true genetic effects for genes underlying complex traits. By employing a simple population genetics model, we explore the effects and the conditions of population admixture in masking, changing, or even reversing true genetic effects of genes underlying complex traits.
Insertional Mutagenesis of Genes Required for Seed Development in Arabidopsis thaliana
Authors: McElver John , Tzafrir Iris , Aux George , Rogers Rebecca , Ashby Carl , Smith Kelsey , Thomas Carla , Schetter Amy , Zhou Qing , Cushman Mary Ann , Tossberg John , Nickle Todd , Levin Joshua Z , Law Marcus , Meinke David , Patton David 
Published: April 2021

Abstract
The purpose of this project was to identify large numbers of Arabidopsis genes with essential functions during seed development. More than 120,000 T-DNA insertion lines were generated following Agrobacterium-mediated transformation. Transgenic plants were screened for defective seeds and putative mutants were subjected to detailed analysis in subsequent generations. Plasmid rescue and TAIL-PCR were used to recover plant sequences flanking insertion sites in tagged mutants. More than 4200 mutants with a wide range of seed phenotypes were identified. Over 1700 of these mutants were analyzed in detail. The 350 tagged embryo-defective (emb) mutants identified to date represent a significant advance toward saturation mutagenesis of EMB genes in Arabidopsis. Plant sequences adjacent to T-DNA borders in mutants with confirmed insertion sites were used to map genome locations and establish tentative identities for 167 EMB genes with diverse biological functions. The frequency of duplicate mutant alleles recovered is consistent with a relatively small number of essential (EMB) genes with nonredundant functions during seed development. Other functions critical to seed development in Arabidopsis may be protected from deleterious mutations by extensive genome duplications.