G3: Genes|Genomes|Genetics最新文献

{"title":"The influence of Polycomb and Trithorax group function on the sexually dimorphic abdomen pigmentation of Drosophila melanogaster.","authors":"Devon M Seibert, Ashley V Williams, Madeline A Ranly, Melissa E Williams, Claire C Konys, Michael L Weinstein, Jenna R Rock, Rachel M Stanojev, Corinne R Stone, Emily B Daniel, Eliana G Williams, Mark Rebeiz, Thomas M Williams","doi":"10.1093/g3journal/jkag218","DOIUrl":"10.1093/g3journal/jkag218","url":null,"abstract":"<p><p>Animal traits develop through intricate patterns of gene expression that are regulated at multiple levels. This regulation includes interactions between transcription factors and cis-regulatory element DNA sequences and the dynamic accessibility of cis-regulatory elements due to chromatin modifications and remodeling. Polycomb group and Trithorax group genes are evolutionarily conserved regulators of chromatin state. Although the Polycomb group and Trithorax group genes have well understood roles in developmental gene regulation, the extent to which these complexes contribute to trait evolution remains unclear. Here, we performed a genetic screen to understand how Polycomb group and Trithorax group genes shape the rapidly evolving gene regulatory network responsible for the dimorphic abdomen tergite pigmentation of Drosophila melanogaster fruit flies. A near-comprehensive screen of Trithorax group and Polycomb group genes was conducted using RNAi, and numerous genes were identified whose reduced expression caused alterations to tergite pigmentation. For the 8 most impactful genes, their roles in regulating this gene regulatory network were explored. We assessed their effects on several key transcription factors and downstream cis-regulatory elements that are responsible for the expression of the gene regulatory network's pigmentation enzyme genes. We show that multiple members of the Polycomb group and Trithorax group complexes are required for distinct tiers in the pigmentation gene regulatory network, suggesting potential points where responsive elements for different factors may have evolved. The results set the stage for future studies to identify the direct gene regulatory network targets of Polycomb group and Trithorax group complexes and how they have participated in the evolution of this gene regulatory network.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643780/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148689014","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":"Sequence effects on mutation rates investigated in whole-genome sequenced UK Biobank participants.","authors":"David Curtis","doi":"10.1093/g3journal/jkag207","DOIUrl":"10.1093/g3journal/jkag207","url":null,"abstract":"<p><p>UK Biobank has released whole-genome sequence data for 500,000 participants, including allele counts for hundreds of millions of variants and these were considered in the context of the pentanucleotide background on which they occurred. Variants with an allele count of 25 were found to closely mirror previously reported de novo mutations (DNMs) in terms of the frequencies of variant types. Therefore these variants, referred to as AC25 variants, were used to investigate factors relevant to mutation frequency. The counts of AC25 variant types in a trinucleotide context could be well approximated by combining 7 mutational signatures previously obtained from studies of cancer cells. Frequencies of variants were strongly influenced by context. C > T variants occurred more often in the CpG context but other features of the trinucleotide context also had marked effects. Although the trinucleotide context was a very strong predictor of the variant frequencies for the full pentanucleotide context, there were examples where the more distant nucleotides did have marked effects. Here, the configuration of bases 2 upstream or downstream could have a more than 2-fold effect on variant frequencies, presumed to reflect mutation rates. For some variants frequencies varied between nontranscribed and transcribed regions and variants with higher frequencies in transcripts of protein coding genes also demonstrated strand asymmetry, being more frequent on the coding than template strand. Genes with high frequencies of these variants showed enrichment for basic cellular processes, meaning that they could have arisen as a result of transcriptional events during embryogenesis prior to entering the germline. Investigating the molecular mechanisms whereby contexts moderate mutation rates could lead to a better understanding of variant pathogenicity and how DNA fidelity is conserved in normal tissue. This research has been conducted using the UK Biobank Resource.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643795/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148601303","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":"Correction to: Pseudomonas aeruginosa adaptation and persistence in the aspergilloma microbiome revealed by integrated multi-omics.","authors":"","doi":"10.1093/g3journal/jkag236","DOIUrl":"10.1093/g3journal/jkag236","url":null,"abstract":"","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643762/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148891184","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":"Resampling-based evaluation of a 79-SNP panel for hybrid classification across generations: a case study in European lobster (Homarus gammarus).","authors":"Erik Sandertun Røed, Charlie D Ellis, Jamie R Stevens, Louise Chavarie, Marie Saitou","doi":"10.1093/g3journal/jkag206","DOIUrl":"10.1093/g3journal/jkag206","url":null,"abstract":"<p><p>Accurate detection of hybridization and introgression is critical not only for basic research, but also for fisheries management. In many species, however, hybrid ancestry is difficult to detect beyond the F1 generation, especially when based on limited genetic markers. In European waters, hybridization between the native Homarus gammarus and the introduced H. americanus poses a direct risk to the integrity of native stocks and effective fishery management, yet detection methods are often limited to morphological traits or first-generation hybrids. A set of 79 SNPs originally developed for population genetic analyzes in H. gammarus and subsequently applied to distinguish H. gammarus, H. americanus, and F1 individuals has shown promise, but its capacity to resolve later-generation backcrosses remains untested. Here, we evaluated this panel's performance under the allele-frequency distributions and marker properties observed in the empirical dataset it was based on, using individual-based resampling to generate genotypes with known ancestry proportions. We show that the panel retains discriminatory power for broad ancestry classes and early-generation hybrids, but with reduced accuracy for later-generation backcrosses and especially high uncertainty in distinguishing backcrosses toward H. gammarus from variation within the H. gammarus parental reference. These findings provide an assessment of hybrid classification performance for this specific panel and demonstrate the value of empirical resampling simulations for identifying both the utility and the limitations of existing marker panels in fisheries-relevant species.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13643775/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148601215","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":"Large transgene arrays cause aberrant transcription and synthetic molting defects.","authors":"Iskra Katic, Panagiotis Papasaikas, Dimos Gaidatzis, Helge Großhans","doi":"10.1093/g3journal/jkag285","DOIUrl":"10.1093/g3journal/jkag285","url":null,"abstract":"<p><p>Multicopy transgene arrays remain widely used in Caenorhabditis elegans research. It is usually assumed that they behave neutrally, not impacting the phenotype under investigation. Here, we reveal that a previously reported heterochronic extra-molt phenotype associated with myrf-1(mg412) depends on the presence of the integrated molting reporter mgIs49. Nanopore long-read sequencing shows that mgIs49 is a massive 8.8-Mb insertion - around 50% of the size of its host chromosome - which disrupts the prmt-9 gene. Both mgIs49 and another array, maIs105, cause dysregulation of the transcriptome and accumulation of reads mapping in sense-direction to transgene promoter sequences. We identify additional arrays exceeding 4 Mb and show that variable molting defects occur across different transgenic lines when combined with myrf-1(mg412), implicating array size or composition in the synthetic phenotype. Our results underscore the necessity of replacing multicopy reporters in developmental studies with single-copy insertions or endogenous tagging whenever possible.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106886","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":"Age-specific genomic and transcriptomic variation reveals limited evidence for cis-regulatory interactions modulating aging in Saccharomyces cerevisiae.","authors":"Kaitlin M McHugh, Felipe S Barreto, Molly K Burke","doi":"10.1093/g3journal/jkag276","DOIUrl":"https://doi.org/10.1093/g3journal/jkag276","url":null,"abstract":"<p><p>The budding yeast Saccharomyces cerevisiae is a well-established model for studying the genetic basis of complex traits, and it is a powerful system for investigating mechanisms of aging. Here, we examine the genomic and transcriptomic factors contributing to increased replicative age in recombinant yeast populations harboring standing genetic variation. Using Fluorescence-Activated Cell Sorting (FACS), we isolated young and aged cohort pairs across twelve biological replicates and sequenced their progeny to assess patterns of differentiation at the nucleotide and transcription levels. Most differentiated alleles were located in coding regions, including significant variants within 132 unique genes. Transcriptomic analysis revealed 60 differentially expressed genes in aged populations, including 18 genes with increased expression in aged cohorts, and 42 genes with decreased expression. Although only two genes (RFA3 and WSC4) were implicated in both genomic and transcriptomic analyses, functional overlap associated with protein homeostasis, DNA repair, and cell cycle regulation was evident across datasets. Notably, we found no strong evidence that differentially expressed genes were more likely to occur in close proximity to significant gene variants. This suggests that late-life survival is not predominantly governed by background-independent local cis-regulatory interactions. These findings are consistent with a polygenic architecture in which distinct genotypes may promote longevity through diverse regulatory mechanisms.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106869","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":"Identification of a novel solid stem QTL in hexaploid wheat contributing resistance to wheat stem sawfly.","authors":"Ishita Isha, Jason Fiedler, Raja Sekhar Nandety, Jennifer Lachowiec, Jessica Kansman, Nancy Blake, Hwa Young Heo, Lucas A Wright, Jason P Cook","doi":"10.1093/g3journal/jkag282","DOIUrl":"https://doi.org/10.1093/g3journal/jkag282","url":null,"abstract":"<p><p>Stem solidness is a heritable quantitative trait that provides resistance against wheat stem sawfly (WSS) infestation in durum and hexaploid wheat. Stem solidness arises from the action of multiple genetic regions contributing to temporal stem pith production, identified in ancient landraces and cultivars of wheat. However, uniform expression of stem pith across all internodes and throughout wheat's lifecycle remain unobserved. In the present study, we dissected the genetic architecture of the solid stem trait by leveraging a cultivar from the International Maize and Wheat Improvement Center, 'CIMMYT-9263'. A recombinant inbred mapping population comprising 146 lines was created by crossing 'CIMMYT-9263' with a Montana adapted, photoperiod-insensitive, WSS susceptible variety, 'Hi-Line'. Multi-year phenotypic assessment of the solid stem trait at stem elongation (Zadoks 32) and maturity (Zadoks 77), along with WSS field stem cutting (%), revealed QTL regions contributing to host plant resistance. We report a major QTL region on the long arm of chromosome 3A spanning the physical distance 730,477,755 - 739,555,941 bp, named, Qss.msub.3AL-2. The allele Qss.msub.3AL-2.b contributed from the 'CIMMYT-9263' controls for increased stem pith production and reduced stem cutting. Markers associated with the Qss.msub.3AL-2.b solid stem allele were used to create Kompetetive Allele Specific Primers (KASP) for marker assisted selection (MAS). A small effect QTL on chromosome 3D was also identified controlling for temporal stem solidness. The two solid stem QTL identified in the present study will contribute to creating cultivars carrying multiple solid stem alleles for improving WSS resistance.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106847","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":"S. cerevisiae Cwc15p Tunes the Spliceosome Active Site for Remodeling and Catalysis.","authors":"Natalie J Zeps, Giovanni Balice, Elizabeth C Baudhuin, Zach Freedman, Sierra Jones, Dennis Halterman, Aaron A Hoskins","doi":"10.1093/g3journal/jkag280","DOIUrl":"https://doi.org/10.1093/g3journal/jkag280","url":null,"abstract":"<p><p>Pre-mRNA splicing is an essential step in eukaryotic gene expression during which spliceosomes remove introns from nascent RNAs while ligating the adjacent exons. Spliceosomes are cellular nanomachines composed of five small nuclear (snRNA) components and dozens of proteins, most of which are highly conserved. Despite the high conservation of many splicing factors between S. cerevisiae and H. sapiens, several protein components of the S. cerevisiae spliceosome are not essential for growth under normal laboratory conditions. This is particularly surprising for nonessential factors whose conserved domains contact the spliceosome's catalytic core. Uncovering a function for these splicing factors can be challenging since they are not required for viability, may engage in functionally redundant interactions, and may display only weak phenotypes in the absence of secondary mutations in other spliceosome components. One such nonessential factor is the Cwc15 protein. Cwc15's highly conserved N-terminus directly contacts the U2/U6 di-snRNA within the spliceosome catalytic core; yet its precise role in splicing has not been defined in any organism. In this work, we use molecular genetics in S. cerevisiae combined with splicing reporter assays to study Cwc15p function. We propose that Cwc15p not only promotes the stability of the active site but also its structural transitions. These functions may be critical for splicing in S. cerevisiae under nonoptimal conditions, facilitating use of weak or alternate splice sites, and could have implications for proofreading of spliceosome active site formation.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106965","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 genetic screen for suppressors of neuron degeneration in a C. elegans sod-1G85R model of Amyotrophic Lateral Sclerosis.","authors":"Katherine S Yanagi, Alexander T Lin-Moore, Nijpawi C Gordon, Jeremy J Lins, Emma Michaela Coyne, Kathleen L Meininger, Stephanie L Moy, Loraina A Stinson, Melissa B Walsh, Mika Gallati, Animesh Mahapatra, Ruka Aderogba, Alexander Jaworski, Anne C Hart","doi":"10.1093/g3journal/jkag281","DOIUrl":"https://doi.org/10.1093/g3journal/jkag281","url":null,"abstract":"<p><p>Genetic variants in superoxide dismutase 1 (SOD1) cause the progressive neurodegenerative disease Amyotrophic Lateral Sclerosis (ALS). Treatments for this disease are limited, and the unique vulnerability of cholinergic and glutamatergic motor neurons to degeneration seen in ALS patients is not clearly understood. Identifying genetic modifiers of neurodegeneration can provide insight into the selective vulnerability of motor neurons in ALS and may accelerate identification of novel therapeutic targets. Here, we describe a forward genetic screen for suppressors of the stress-induced glutamatergic neuron degeneration in a single-copy C. elegans model of sod-1G85R. Used two different screening strategies, we identified 53 suppressor lines that decreased glutamatergic neuron degeneration to varying degrees. To rapidly identify suppressor genes, we sequenced suppressor lines and identified candidate suppressor genes based on frequency of de novo exonic mutations and previously published work. Two candidates were tested and excluded as suppressor genes: erh-1 and imph-1. For a subset of unidentified suppressor lines, we determined if cholinergic neurodegeneration was also suppressed; roughly one-third of suppressor lines showed no corresponding cholinergic neuron rescue, suggesting that mechanisms involved in cholinergic and glutamatergic degeneration are at least partially divergent. This study outlines the first unbiased genetic screen in a knock-in model of SOD1 neurodegeneration, describes a cohort of candidate suppressor lines with decreased SOD1-dependent neurodegeneration, excludes two candidates and discusses approaches for suppressor mutation isolation and gene identification.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149106876","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":"Conditional AGO Knockout Reveals Tissue-Specific Requirements of miRNA Activity in C. elegans.","authors":"Yimeng Gao, Yuchuan Bai, Xiaokun Zhang, Yiru Jiang, Yongbin Li","doi":"10.1093/g3journal/jkag279","DOIUrl":"https://doi.org/10.1093/g3journal/jkag279","url":null,"abstract":"<p><p>MicroRNAs (miRNAs) are essential for worm development, yet their roles remain unclear in most tissues. Here, we established a tissue-specific Argonaute (AGO) knockout system in Caenorhabditis elegans using conditional deletion of alg-1 in an alg-2 mutant background. Tissue-restricted loss of AGO revealed distinct developmental and tissue-specific phenotypes. AGO depletion in the intestine, pharynx, and hypodermis caused developmental arrest and tissue-specific defects, whereas neuronal and muscle-specific AGO depletion impaired locomotion and affected neuronal or muscle-associated phenotypes. Moreover, combined loss of selected tissue-expressed miRNAs only partially recapitulated the corresponding AGO-depletion phenotypes. Muscle-specific re-expression of selected miRNAs rescued the locomotion defect of the compound miRNA mutant. This study establishes a platform for dissecting tissue-specific miRNA functions during animal development.</p>","PeriodicalId":12468,"journal":{"name":"G3: Genes|Genomes|Genetics","volume":" ","pages":""},"PeriodicalIF":2.4,"publicationDate":"2026-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"149080223","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}