Genetics最新文献

{"title":"A fission yeast CENP-B homologue Abp1 prevents RNAi-mediated heterochromatin formation at ribosomal DNA repeats.","authors":"Satoru Tsunemine, Miyuki Mori, Yota Murakami","doi":"10.1093/genetics/iyaf050","DOIUrl":"https://doi.org/10.1093/genetics/iyaf050","url":null,"abstract":"<p><p>In response to nutritional starvation, living cells sensitively regulate the production rates of molecules required for survival. Under glucose starvation, a facultative heterochromatinization of ribosomal DNA (rDNA) is considered to regulate ribosomal RNA (rRNA) production. However, the molecular mechanism is still unclear. Here, we report a novel function of CENP-B homologue Abp1 in forming facultative heterochromatin at rDNA repeats. We find that loss of Abp1 induces an ectopic nucleosome assembly at rDNA repeats. Interestingly, loss of Abp1 induces two mutually exclusive changes at rDNA repeats: an excess accumulation of methylation of histone H3 at lysine 9 (H3K9me), a hallmark of heterochromatin, and an active RNA polymerase II (RNAPII) transcription. This excess heterochromatin represses rRNA expression and requires RNAi machinery for its formation. Furthermore, we show that the excess heterochromatin does not affect cellular viability under glucose starvation but prevents the return to the proliferation cycle in recovering glucose-rich conditions. Since glucose starvation rapidly induces partial Abp1 disassociation from rDNA repeats, we propose that Abp1 regulates an activity of RNAPII transcription that is paradoxically required for RNAi-mediated heterochromatin formation and controls an appropriate level of heterochromatinization at rDNA repeats under glucose starvation.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711822","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Vitamin B12 partially rescues embryonic cell migration defects in C. elegans ephrin mutants by improving propionic acid breakdown and one-carbon cycle metabolism.","authors":"Tushar H Ganjawala, Erin Hsiao, Prativa Amom, Radmehr Molaei, Samantha Goodwin, Amanda L Zacharias","doi":"10.1093/genetics/iyaf054","DOIUrl":"https://doi.org/10.1093/genetics/iyaf054","url":null,"abstract":"<p><p>Successful cell migration followed by cell adhesion and tissue remodeling is required for organogenesis in a number of tissues, many of which are susceptible to gene-environment interactions resulting in congenital anomalies. In C. elegans embryogenesis, one such event is the closure of the ventral cleft, an essential first step in morphogenesis; this process depends on ephrin signaling, but no single gene mutation is fully penetrant embryonic lethal, likely due to redundancy with semaphorin and Robo signaling. We exposed hermaphrodites mutant for vab-1, the C. elegans ephrin receptor, to various environmental conditions and found vitamin B12 supplementation could partially rescue the embryonic lethality of multiple alleles improving survival by 58%. Vitamin B12 improved the frequency of ventral cleft closure by promoting cell positions more similar to wildtype and increasing cell migration. We found vitamin B12 partially rescued the embryonic lethality of other ephrin pathway mutants as well as semaphorin and robo mutants, but not mutants with ventral cleft defects due to cell adhesion or cell fate defects. We found rescue by vitamin B12 depends on its functions in both mitochondrial propionic acid breakdown and the one-carbon cycle, and antioxidant treatment can also partially rescue ephrin pathway mutants. These results are distinct from the larval response to vitamin B12, which depends only on the one-carbon cycle, emphasizing the unique metabolism of embryos and particularly the metabolic needs of migrating cells. Overall, our findings highlight the C. elegans embryo as a model system to investigate gene-environment interactions and developmental metabolism.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143711823","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Diverse modes of gene action contribute to heterosis for quantitative disease resistance in maize.","authors":"Asher I Hudson, Maggie R Wagner, Shannon Sermons, Peter J Balint-Kurti","doi":"10.1093/genetics/iyaf049","DOIUrl":"https://doi.org/10.1093/genetics/iyaf049","url":null,"abstract":"<p><p>Disease resistance in plants can be conferred by single genes of large effect or by multiple genes each conferring incomplete resistance. The latter case, termed quantitative resistance, may be difficult for pathogens to overcome through evolution due to the low selection pressures exerted by the actions of any single gene and, for some diseases, is the only identified source of genetic resistance. We evaluated quantitative resistance to two diseases of maize in a bi-parental mapping population as well as backcrosses to both the parents. Quantitative trait locus analysis shows that the genetic architecture of resistance to these diseases is characterized by several modes of gene action including additivity as well as dominance, overdominance, and epistasis. Heterosis or hybrid vigor, the improved performance of a hybrid compared to its parents, can be caused by non-additive gene action and is fundamental to the breeding of several crops including maize. In the backcross populations and a diverse set of maize hybrids, we find heterosis for resistance in many cases and that the degree of heterosis appears to be dependent on both hybrid genotype and disease.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143701845","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A model of Hill-Robertson interference caused by purifying selection in a non-recombining genome.","authors":"Hannes Becher, Brian Charlesworth","doi":"10.1093/genetics/iyaf048","DOIUrl":"https://doi.org/10.1093/genetics/iyaf048","url":null,"abstract":"<p><p>A new approach to modeling the effects of Hill-Robertson interference on levels of adaptation and patterns of variability in a non-recombining genome or genomic region is described. The model assumes a set of L diallelic sites subject to reversible mutations between beneficial and deleterious alleles, with the same selection coefficient at each site. The assumption of reversibility allows the system to reach a stable statistical equilibrium with respect to the frequencies of deleterious mutations, in contrast to many previous models that assume irreversible mutations to deleterious alleles. The model is therefore appropriate for understanding the long-term properties of non-recombining genomes such as Y chromosomes, and is applicable to haploid genomes or to diploid genomes when there is intermediate dominance with respect to the effects of mutations on fitness. Approximations are derived for the equilibrium frequencies of deleterious mutations, the effective population size that controls the fixation probabilities of mutations at sites under selection, the nucleotide site diversity at neutral sites located within the non-recombining region, and the site frequency spectrum for segregating neutral variants. The approximations take into account the effects of linkage disequilibrium on the genetic variance at sites under selection. Comparisons with published and new computer simulation results show that the approximations are sufficiently accurate to be useful, and can provide insights into a wider range of parameter sets than is accessible by simulation. The relevance of the findings to data on non-recombining genome regions is discussed.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694244","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two eIF4E paralogs occupy separate germ granule mRNPs that mediate mRNA repression and translational activation.","authors":"Gita Gajjar, Hayden P Huggins, Eun Suk Kim, Weihua Huang, Frederic X Bonnet, Dustin L Updike, Brett D Keiper","doi":"10.1093/genetics/iyaf053","DOIUrl":"https://doi.org/10.1093/genetics/iyaf053","url":null,"abstract":"<p><p>We studied translation factor eIF4E paralogs that regulate germline mRNAs. Translational control of mRNAs is essential for germ cell differentiation and embryogenesis. Messenger ribonucleoprotein (mRNP) complexes assemble on mRNAs in the nucleus, as they exit via perinuclear germ granules, and in the cytoplasm. Bound mRNP proteins including eIF4Es exert both positive and negative post-transcriptional regulation. In C. elegans, germ granules are surprisingly dynamic mRNP condensates that remodel during development. Two eIF4E paralogs (IFE-1 and IFE-3), their cognate eIF4E-Interacting Proteins (4EIPs), and polyadenylated mRNAs are present in germ granules. Affinity purification of IFE-1 and IFE-3 mRNPs allowed mass spectrometry and mRNA-Seq to identify other proteins and the mRNAs that populate stable eIF4E complexes. We find translationally repressed mRNAs (e.g. pos-1, mex-3, spn-4, etc.) enriched with IFE-3, but excluded from IFE-1. Identified mRNAs overlap substantially with mRNAs previously described to be IFE-1-dependent for translation. The findings suggest that oocytes and embryos utilize the two eIF4Es for opposite purposes on critically regulated germline mRNAs. Sublocalization within adult perinuclear germ granules suggests an architecture in which Vasa/GLH-1, PGL-1 and the IFEs are stratified, which may facilitate sequential remodeling of mRNPs leaving the nucleus. Biochemical composition of isolated mRNPs indicates opposing yet cooperative roles for the two eIF4Es. We propose that the IFEs accompany controlled mRNAs in the repressed or activated state during transit to the cytoplasm. Copurification of IFE-1 with IFE-3 suggests they may interact to move repressed mRNAs to ribosomes.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677390","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mediator-29 Limits Caenorhabditis elegans Fecundity.","authors":"Qi Fan, Christopher Tran, Wei Cao, Roger Pocock","doi":"10.1093/genetics/iyaf051","DOIUrl":"https://doi.org/10.1093/genetics/iyaf051","url":null,"abstract":"<p><p>Mediator is an evolutionarily conserved multiprotein complex that acts as a critical coregulator of RNA polymerase II-mediated transcription. While core Mediator components are broadly required for transcription, others govern specific regulatory modules and signalling pathways. Here, we investigated the function of MDT-29/MED29 in the Caenorhabditis elegans germ line. We found that endogenously-tagged MDT-29 is ubiquitously expressed and concentrated in discrete foci within germ cell nuclei. Functionally, depleting MDT-29 in the germ line during larval development boosted fecundity. We determined that the increase in progeny production was likely caused by a combination of an expanded germline stem cell pool and decreased germ cell apoptosis. Thus, MDT-29 may act to optimize specific gene expression programs to control distinct germ cell behaviors, providing flexibility to progeny production in certain environments.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143694245","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fork-barrier-independent roles of topoisomerase I in the ribosomal DNA.","authors":"Temistocles Molinar, Daniel Sultanov, Hannah Klein, Andreas Hochwagen","doi":"10.1093/genetics/iyaf052","DOIUrl":"https://doi.org/10.1093/genetics/iyaf052","url":null,"abstract":"<p><p>Topoisomerase I, a nickase that allows swiveling of the DNA substrate, is highly enriched in the ribosomal DNA (rDNA) from yeast to humans, but its function at this locus remains poorly understood. S. cerevisiae mutants lacking topoisomerase I (top1) exhibit pronounced rDNA instability and accumulate bubbles of single-stranded DNA (ssDNA) on 35S ribosomal RNA genes, suggesting a role in relieving transcription-associated topological stress. However, Top1-cleavage complexes are most highly enriched in the rDNA-encoded replication-fork barrier, a genetically encoded source of rDNA instability, and only weakly in the 35S promoter, leading to the proposal that top1-associated rDNA instability may be linked to the fork barrier. Here, we show that the rDNA instability phenotypes of top1 mutants, including increased formation of extrachromosomal rDNA circles, elevated genetic marker loss, and instability of critically short rDNA arrays, are independent of the replication fork barrier. In addition, we link Top1 binding at the 35S promoter to the formation of a DNA species with a long ssDNA tail, which originates in the 35S promoter region and is undetectable in top1 mutants. This DNA species is abundant in wild-type cells, occurs independently of S phase, and may be the resolution product of the ssDNA bubbles seen in top1 mutants. Whether formation of this DNA species is important for rDNA stability remains unclear, but our findings link Top1 to highly active DNA metabolism in the 35S promoter.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143677389","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New perspectives on Drosophila melanogaster de novo gene origination revealed by investigation of ancient African genetic variation.","authors":"Julie M Cridland, Elizabeth S Polston, David J Begun","doi":"10.1093/genetics/iyaf044","DOIUrl":"https://doi.org/10.1093/genetics/iyaf044","url":null,"abstract":"<p><p>De novo genes can be defined as sequences producing evolutionarily derived transcripts that are not homologous to transcripts produced in an ancestor. While they appear to be taxonomically widespread, there is little agreement regarding their abundance, their persistence times in genomes, the population genetic processes responsible for their spread or loss, or their possible functions. In Drosophila melanogaster, two approaches have been used to discover these genes and investigate their properties. One uses traditional comparative approaches and existing genomic resources and annotations. A second approach uses raw transcriptome data to discover unannotated genes for which there is no evidence of presence in related species. Investigations using the second approach have focused on D. melanogaster genotypes from recently established cosmopolitan populations. However, most of the genetic variation in the species is found in African populations, suggesting the possibility that fuller understanding of genetic novelties in the species may follow from studies of these populations. Here we investigate de novo gene candidates expressed in testis and accessory glands in a sample of flies from Zambia and compare them to candidate de novo genes expressed in North American populations. We report a large number of previously undiscovered de novo gene candidates, most of which are expressed polymorphically. Many are predicted to code for secreted proteins. In spite of much different levels of genomic variation in Zambian and North American populations, they express similar numbers of candidate de novo genes. We find evidence from genetic analysis of Raleigh inbred lines that a fraction of rarely expressed gene candidates in this population represent deleterious transcription promoted by inbreeding depression. Many de novo gene candidates are expressed in multiple tissues and both sexes, raising questions about how they may interact with natural selection. The relative importance of positive and negative selection, however, remains unclear.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143665027","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dynamic regulation of murine RNA Polymerase III transcription during heat shock stress.","authors":"Thomas F Nguyen, James Z J Kwan, Jennifer E Mitchell, Jieying H Cui, Sheila S Teves","doi":"10.1093/genetics/iyaf042","DOIUrl":"https://doi.org/10.1093/genetics/iyaf042","url":null,"abstract":"<p><p>Cells respond to many different types of stresses by overhauling gene expression patterns, both at the transcriptional and translational level. Under heat stress, global transcription and translation are inhibited, while the expression of chaperone proteins are preferentially favored. As the direct link between mRNA transcription and protein translation, tRNA expression is intricately regulated during the stress response. Despite extensive research into the heat shock response (HSR), the regulation of tRNA expression by RNA Polymerase III (Pol III) transcription has yet to be fully elucidated in mammalian cells. Here, we examine the regulation of Pol III transcription during different stages of heat shock stress in mouse embryonic stem cells (mESCs). We observe that Pol III transcription is downregulated after 30 minutes of heat shock, followed by an overall increase in transcription after 60 minutes of heat shock. This effect is more evident in tRNAs, though other Pol III gene targets are also similarly affected. Notably, we show that the downregulation at 30 minutes of heat shock is independent of HSF1, the master transcription factor of the HSR, but that the subsequent increase in expression at 60 minutes requires HSF1. Taken together, these results demonstrate an adaptive RNA Pol III response to heat stress, and an intricate relationship between the canonical HSR and tRNA expression.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659381","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Theory of Heterosis.","authors":"Zhao-Bang Zeng, Gabriel De Siqueira Gesteira, Lujia Mo, Yingjie Xiao, Jianbing Yan","doi":"10.1093/genetics/iyaf045","DOIUrl":"https://doi.org/10.1093/genetics/iyaf045","url":null,"abstract":"<p><p>Heterosis refers to the superior performance of a hybrid over its parents. It is the basis for hybrid breeding particularly for maize and rice. Genetically it is due to interactions between alleles of quantitative trait loci (QTL) (dominance and epistasis). Despite enormous interest and efforts to study the genetic basis of heterosis, the relative contribution of dominance vs. epistasis to heterosis is still not clear. This is because most published studies estimate QTL effects in pieces, not able to put them together to assess the overall pattern adequately. We propose a theoretical framework that focuses on the inference of the relationship between genome and traits that includes the identification of multiple QTL and estimation of the whole set of QTL (additive, dominant, and epistatic) effects. Used for heterosis, it gives a clear genetic definition and interpretation of heterosis. We applied the theory and methods to a large maize dataset with a factorial design of many male and female inbred lines and their hybrid crosses. Heterosis of ear weight in maize is primarily due to QTL dominant effects, many are over-dominant. The contribution to heterosis due to epistasis is small and diffused. For comparison, we also analyzed a rice dataset that is an F2-type population derived from a cross between two inbred lines. The result indicates that dominance is still the main contributor to heterosis, and epistasis contribution is small.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-03-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143659377","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}