Genetics最新文献

{"title":"Molecular evolution of a reproductive barrier in maize and related species.","authors":"Elli Cryan, Garnet Phinney, Arun S Seetharam, Matthew M S Evans, Elizabeth A Kellogg, Junpeng Zhan, Blake C Meyers, Daniel J Kliebenstein, Jeffrey Ross-Ibarra","doi":"10.1093/genetics/iyaf085","DOIUrl":"https://doi.org/10.1093/genetics/iyaf085","url":null,"abstract":"<p><p>Three cross-incompatibility loci each control a distinct reproductive barrier in both domesticated maize (Zea mays ssp. mays) and its wild teosinte relatives. These three loci, Teosinte crossing barrier1 (Tcb1), Gametophytic factor1 (Ga1), and Ga2, each play a key role in preventing hybridization between incompatible populations and are proposed to maintain the barrier between domesticated and wild subspecies. Each locus encodes both a silk-active and a matching pollen-active pectin methylesterase (PMEs). To investigate the diversity and molecular evolution of these gametophytic factor loci, we identified existing and improved models of the responsible genes in a new genome assembly of maize line P8860 that contains active versions of all three loci. We then examined fifty-two assembled genomes from seventeen species to classify haplotype diversity and identify sites under diversifying selection during the evolution of these genes. We show that Ga2, the oldest of these three loci, was duplicated to form Ga1 at least 12 million years ago. Tcb1, the youngest locus, arose as a duplicate of Ga1 before or around the time of diversification of the Zea genus. We find evidence of positive selection during evolution of the functional genes at an active site in the pollen-expressed PME and predicted surface sites in both the silk- and pollen-expressed PMEs. The most common allele at the Ga1 locus is a conserved ga1 allele (ga1-Off), which is specific haplotype containing three full-length PME gene copies, all of which are non-coding due to conserved stop codons and are between 610 thousand and 1.5 million years old. We show that the ga1-Off allele is associated with and likely generates 24-nt siRNAs in developing pollen-producing tissue, and these siRNAs map to functional Ga1 alleles. In previously-published crosses, the ga1-Off allele was associated with reduced function of the typically dominant functional alleles for the Ga1 and Tcb1 barriers. Taken together, this seems to be an example of an allele at a reproductive barrier locus being associated with an as yet undetermined mechanism capable of silencing the reproductive barrier.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144065159","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":"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 levels. Under heat stress, global transcription and translation are inhibited, while the expression of chaperone proteins is preferentially favored. As the direct link between mRNA transcription and protein translation, transfer RNA (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. We observe that Pol III transcription is downregulated after 30 min of heat shock, followed by an overall increase in transcription after 60 min of heat shock. This effect is more evident in tRNAs, although other Pol III gene targets are also similarly affected. Notably, we show that the downregulation at 30 min of heat shock is independent of HSF1, the master transcription factor of the HSR, but that the subsequent increase in expression at 60 min 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":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059648/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Yeast molecular genetic tricks to study gene regulation.","authors":"Kevin Struhl","doi":"10.1093/genetics/iyaf041","DOIUrl":"10.1093/genetics/iyaf041","url":null,"abstract":"<p><p>The Genetics Society of America's (GSA) Edward Novitski Prize is awarded to researchers for extraordinary creativity and intellectual ingenuity in genetics research. Struhl is being recognized for his pioneering work cloning a functional eukaryotic gene in E. coli, defining its promoter and regulatory region, and using random DNA and amino acid sequences to define determinants of specificity. The award also recognizes other key scientific contributions including Struhl's discovery of the sequences and protein interactions required for transcriptional activation and repression and demonstrating the importance of nucleosome-free regions for transcription initiation, among others.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143732682","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":"GWAS significance thresholds in large cohorts of European ancestry.","authors":"Evans K Cheruiyot, Tingyan Yang, Allan F McRae","doi":"10.1093/genetics/iyaf056","DOIUrl":"10.1093/genetics/iyaf056","url":null,"abstract":"<p><p>While the P-value threshold of 5.0×10-8 remains the standard for genome-wide association studies (GWAS) in humans and other species, it still needs to be updated to reflect the current era of large-scale GWAS, where tens of thousands of sample sizes are used to discover genetic associations at loci with smaller minor allele frequencies. In this study, we used a dataset of 348,501 individuals of European ancestry from the UK Biobank to determine the GWAS thresholds required for multiple testing corrections when considering rare and common variants in additive and dominant GWAS models. Additionally, we employed conditional and joint analysis to quantify the proportion of false significant hits in the GWAS results for 72 traits in the UK Biobank when applying the traditional GWAS cutoff vs our newly proposed P-value thresholds. Overall, the results indicate that the conventional GWAS significance threshold of 5.0×10-8 yields a false-positive rate of between 20% and 30% in GWAS studies that utilize large sample sizes and less common variants. Instead, a more stringent GWAS P-value threshold of 5.0×10-9 is needed when rare variants (with minor allele frequency > 0.1%) are included in the association test for both additive and dominance models within the European ancestry population. However, further validation across diverse datasets and study designs, is needed to evaluate the broader applicability of this proposed threshold.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143721916","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A fission yeast CENP-B homolog Abp1 prevents RNAi-mediated heterochromatin formation at ribosomal DNA repeats.","authors":"Satoru Tsunemine, Miyuki Mori, Yota Murakami","doi":"10.1093/genetics/iyaf050","DOIUrl":"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 is considered to regulate ribosomal RNA production. However, the molecular mechanism is still unclear. Here, we report a novel function of CENP-B homolog Abp1 in forming facultative heterochromatin at ribosomal DNA repeats. We find that the loss of Abp1 induces an ectopic nucleosome assembly at rDNA repeats. Interestingly, the loss of Abp1 induces two mutually exclusive changes at ribosomal DNA repeats: an excess accumulation of methylation of histone H3 at lysine 9, a hallmark of heterochromatin, and an active RNA polymerase II transcription. This excess heterochromatin represses ribosomal RNA expression and requires RNA interference 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 ribosomal DNA repeats, we propose that Abp1 regulates activity of RNA polymerase II transcription that is paradoxically required for RNA interference-mediated heterochromatin formation and controls an appropriate level of heterochromatinization at ribosomal DNA repeats under glucose starvation.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","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":"Mediator-29 limits Caenorhabditis elegans fecundity.","authors":"Qi Fan, Christopher Tran, Wei Cao, Roger Pocock","doi":"10.1093/genetics/iyaf051","DOIUrl":"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 signaling 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":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059642/pdf/","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":"OA","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":"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 (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 quantitative trait loci 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 quantitative trait loci and estimation of the whole set of quantitative trait loci (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 quantitative trait loci dominant effects, many are overdominant. 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 2 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":"2025-05-08","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}

{"title":"Two eIF4E paralogs occupy separate germ granule messenger ribonucleoproteins 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":"10.1093/genetics/iyaf053","url":null,"abstract":"<p><p>We studied translation factor eukaryotic initiation factor 4E (eIF4E) paralogs that regulate germline mRNAs. Translational control of mRNAs is essential for germ cell differentiation and embryogenesis. Messenger ribonucleoprotein complexes assemble on mRNAs in the nucleus, as they exit via perinuclear germ granules, and in the cytoplasm. Bound messenger ribonucleoproteins including eIF4E exert both positive and negative posttranscriptional regulation. In Caenorhabditiselegans, germ granules are surprisingly dynamic messenger ribonucleoprotein condensates that remodel during development. Two eIF4E paralogs (IFE-1 and IFE-3), their cognate eIF4E-interacting proteins, and polyadenylated mRNAs are present in germ granules. Affinity purification of IFE-1 and IFE-3 messenger ribonucleoproteins allowed mass spectrometry and mRNA-Seq to identify other proteins and the mRNAs that populate stable eukaryotic initiation factor 4E 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 2 eukaryotic initiation factor 4E paralogs 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 messenger ribonucleoproteins leaving the nucleus. Biochemical composition of isolated messenger ribonucleoproteins indicates opposing yet cooperative roles for the 2 eukaryotic initiation factor 4E paralogs. 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":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059638/pdf/","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":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatin and epigenetics in aging biology.","authors":"Eric Lieberman Greer, Siu Sylvia Lee, Veena Prahlad","doi":"10.1093/genetics/iyaf055","DOIUrl":"https://doi.org/10.1093/genetics/iyaf055","url":null,"abstract":"<p><p>This book chapter will focus on modifications to chromatin itself, how chromatin modifications are regulated, and how these modifications are deciphered by the cell to impact aging. In this chapter, we will review how chromatin modifications change with age, examine how chromatin-modifying enzymes have been shown to regulate aging and healthspan, discuss how some of these epigenetic changes are triggered and how they can regulate the lifespan of the individual and its naïve descendants, and speculate on future directions for the field.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":"230 1","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144055103","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":"Patterns of crossover distribution in Drosophila mauritiana necessitate a re-thinking of the centromere effect on crossing over.","authors":"R Scott Hawley, Andrew Price, Hua Li, Madhav Jagannathan, Cynthia Staber, Stacie E Hughes, Stefanie Williams, Anoja Perera, Rhonda R Egidy, Amanda Lawlor, Danny E Miller, Justin P Blumenstiel","doi":"10.1093/genetics/iyaf039","DOIUrl":"10.1093/genetics/iyaf039","url":null,"abstract":"<p><p>We present an SNP-based crossover map for Drosophila mauritiana. Using females derived by crossing 2 different strains of D. mauritiana, we analyzed crossing over on all 5 major chromosome arms. Analysis of 105 male progeny allowed us to identify 327 crossover chromatids bearing single, double, or triple crossover events, representing 398 crossover events. We mapped the crossovers along these 5 chromosome arms using a genome sequence map that includes the euchromatin-heterochromatin boundary. Confirming previous studies, we show that the overall crossover frequency in D. mauritiana is higher than is seen in Drosophila melanogaster. Much of the increase in exchange frequency in D. mauritiana is due to a greatly diminished centromere effect. Using larval neuroblast metaphases from D. mauritiana-D. melanogaster hybrids we show that the lengths of the pericentromeric heterochromatin do not differ substantially between the species, and thus cannot explain the observed differences in crossover distribution. Using a new and robust maximum likelihood estimation tool for obtaining Weinstein tetrad distributions, we observed an increase in bivalents with 2 or more crossovers when compared with D. melanogaster. This increase in crossing over along the arms of D. mauritiana likely reflects an expansion of the crossover-available euchromatin caused by a difference in the strength of the centromere effect. The crossover pattern in D. mauritiana conflicts with the commonly accepted view of centromeres as strong polar suppressors of exchange (whose intensity is buffered by sequence nonspecific heterochromatin) and demonstrates the importance of expanding such studies into other species of Drosophila.</p>","PeriodicalId":48925,"journal":{"name":"Genetics","volume":" ","pages":""},"PeriodicalIF":3.3,"publicationDate":"2025-05-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12059641/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574440","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}