G3: Genes|Genomes|Genetics最新文献

{"title":"Signatures of selection in pleiotropic genes involved in insect neuronal and immune systems.","authors":"Sowmya Senthilkumar, Reese A Martin, Ann T Tate","doi":"10.1093/g3journal/jkag223","DOIUrl":"10.1093/g3journal/jkag223","url":null,"abstract":"<p><p>Pleiotropy, where a single gene contributes to multiple biological functions, plays a central role in shaping evolutionary constraints. The nervous and immune systems are tightly integrated both functionally and genetically, but it is not clear whether pleiotropy constrains adaptation in each system or contributes to disease. Building on evidence that genes that are pleiotropic between development and immunity in Drosophila melanogaster evolve slower than immune-specific genes, we tested whether pleiotropic neuro-immune genes likewise evolve under stronger purifying selection compared to genes functioning solely in neuronal or immune processes, and whether such evolutionary constraint is associated with human neurological disease. We identified immune, neuronal, and neuro-immune genes in D. melanogaster using gene ontology (GO) annotations, estimated patterns of evolutionary constraint across 12 Drosophila species using dN/dS ratios, and investigated the breadth of their expression across developmental stages as a complementary proxy for pleiotropy. We further curated associations between the human orthologs for these genes and neurological disease and tested whether their evolutionary statistics and pleiotropic status predicted disease involvement. We found that pleiotropic genes exhibited significantly lower dN/dS values and were less stage-specific than nonpleiotropic immune genes. Slower-evolving genes were more likely to be associated with human neurological diseases but this pattern was strongest for nonpleiotropic neuronal genes, suggesting that pleiotropy alone is not the strongest predictor of disease. Our results therefore indicate that dN/dS could be a stronger predictor of disease association than pleiotropy, raising new questions about the maintenance of pleiotropy in evolutionarily dynamic physiological systems.</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/PMC13643757/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148758095","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":"Experimental evolution reveals bifunctional genetic solutions to loss of trpF in Salmonella enterica.","authors":"Joakim Näsvall, Hind Abdalaal","doi":"10.1093/g3journal/jkag167","DOIUrl":"10.1093/g3journal/jkag167","url":null,"abstract":"<p><p>How new gene functions arise while maintaining ancestral biological roles remains a central question in evolutionary genetics. To investigate genetic solutions to the disruption of a biosynthetic pathway without prior genetic bias, we used experimental evolution to study restoration of tryptophan biosynthesis in Salmonella enterica strains lacking the trpF gene. Populations were founded from bacteria carrying wild-type alleles of all relevant genes in their native genomic and regulatory contexts and evolved under conditions selecting for growth without exogenous tryptophan. Across independent populations, mutations in either hisA or trpA enabled growth of ΔtrpF strains in the absence of added tryptophan while retaining sufficient ancestral function to support growth under the same conditions. Whole-genome sequencing and genetic reconstruction showed that these mutant alleles were sufficient to confer the growth-rescue phenotype. Duplication of the target gene was detected in only a single population and showed no evidence of functional divergence. Mutational paths differed between genes: hisA-based solutions arose primarily in mutator backgrounds and were associated with stronger trade-offs with ancestral function, whereas trpA-based solutions were more frequent and often retained native function. Together, these results demonstrate that bifunctional genetic solutions can arise through point mutations in multiple genes during experimental adaptation, illustrating how physiologically relevant multifunctionality can evolve at the gene level without gene duplication.</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/PMC13643763/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148389853","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 chromosome-level genome assembly of Thecaphora frezzii, cause of peanut smut, reveals the largest genome of the true smut fungi.","authors":"Nicholas Greatens, M Brian Couger, Mariano Maestro, Guillermo Cabrera Walsh, Sergio Morichetti, Luke J Tallon, Rebecca S Bennett, Josh P Clevenger, Kelly D Chamberlin, Rachel A Koch Bach","doi":"10.1093/g3journal/jkag217","DOIUrl":"10.1093/g3journal/jkag217","url":null,"abstract":"<p><p>Peanut smut, caused by the fungus Thecaphora frezzii, is a significant disease of peanuts in Argentina. Infected plants have seeds replaced by a mass of dark teliospores, reducing yield and seed quality. Following successful in vitro culture of the fungus in its haploid stage, we produced a chromosome-level genome assembly of the species. We compare this genome to those of 49 other species of true smut fungi, or Ustilaginomycetes, including species of medical, agricultural, and industrial importance, some of which are known as pathogens and others only as saprotrophic yeasts. At almost 39 Mb, T. frezzii has the largest genome of the smut fungi sequenced to date with the most repetitive content. While sharing some core effectors with well-studied Ustilago species and their close allies, T. frezzii possesses a large proportion of predicted effectors unique to the species or genus, suggesting a unique infection strategy. Comparisons among the 50 smut genomes also show that the 14 smut species observed only as yeasts have generally smaller genomes with low repeat content, supporting the hypothesis that some smut fungi are adapted to saprotrophic growth as yeasts. This high quality, annotated genome for T. frezzii will be a valuable resource for investigating the population dynamics and evolution of an economically important pathogen and for illuminating an understudied clade of smut fungi.</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/PMC13643800/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148706101","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":"The SOS response acts as a regulatory switch that balances helicase anti-recombination with transcription-replication conflict resolution activities in Escherichia coli.","authors":"Sebastien Fleurier, Ivan Matic","doi":"10.1093/g3journal/jkag205","DOIUrl":"10.1093/g3journal/jkag205","url":null,"abstract":"<p><p>Transcription-replication conflicts are a major source of genome instability, particularly at highly transcribed ribosomal RNA genes, where RNA polymerase stalling can trigger replication fork collapse and double-strand breaks. We investigated how the SOS DNA damage response regulates the activities of the UvrD, DinG, RecQ, and Rep helicases in Escherichia coli, focusing on their roles in resolving transcription-replication conflicts and repairing double-strand breaks at ribosomal RNA loci. We systematically assessed the contribution of each helicase to cell growth, DNA break formation, SOS induction, and survival. Our results show that SOS induction functions as a regulatory switch, modulating UvrD and DinG activities between protective transcription-replication conflict resolution and detrimental anti-recombination. RecA abundance emerges as the key determinant of this switch. While RecQ consistently promotes genome stability by facilitating timely SOS activation and recombinational repair, Rep primarily supports replisome progression, functioning independently of SOS response status. Under nalidixic acid treatment, where survival relies mainly on double-strand break repair, we observed a similar SOS-dependent modulation of helicase activity, reinforcing this regulatory model. Together, these findings uncover a dynamic regulatory mechanism that fine-tunes helicase activities to resolve transcription-replication conflicts while limiting deleterious anti-recombination, thereby preserving chromosome integrity under transcriptional or antibiotic-induced stress.</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/PMC13643760/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148601238","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":"Loss of ptr-6 restores eggshell integrity and embryonic viability in Caenorhabditis elegans fatty acid synthase mutants.","authors":"Yooseong Wang, Milagros Rincon Paz, Xiao Fan, Harold E Smith, Ricardo Roure, Anushka Patil, Crystal Shao, Christy Shao, Caitlyn Garcia, Ellie N Brill, Ziqi Kyra Zheng, Sophia Monsalve, Samantha H Bruner, Jena Itraish, Sophia R Morton, Xiaofei Bai","doi":"10.1093/g3journal/jkag182","DOIUrl":"10.1093/g3journal/jkag182","url":null,"abstract":"<p><p>Fatty acid synthase is a key rate-limited, dimeric multi-enzyme complex in the de novo lipogenesis pathway. Each fatty acid synthase monomer contains seven catalytic domains, which coordinate the stepwise conversion of acetyl-CoA into fatty acids. While fatty acid synthase has been extensively studied in cultured cells, particularly for its oncogenic role, its functions in the germline and early embryonic development remain elusive. A major challenge is that the fatty acid synthase dysfunction typically causes embryonic lethality in animal models, which complicates detailed functional analysis and the identification of compensatory genetic interactors during development. To overcome this limitation and identify novel genetic suppressors of the FASN gene, we utilized a temperature-sensitive allele, fasn-1(g43ts) (A1424T), in the genetically tractable model Caenorhabditis elegans, to conduct unbiased forward genetic screens. We isolated 22 suppressor lines that significantly restored embryonic viability in the fasn-1(g43ts) mutant at the nonpermissive temperature. Using a combination of molecular inversion probe-mapping genomic mapping and a customized bioinformatic pipeline, we identified six mutations in the ptr-6 gene, which encodes a protein containing a patched domain associated with the Hedgehog-like signaling pathway. To validate this genetic suppression, we recreated one of the loss-of-function mutations, ptr-6[W701*], in the fasn-1(g43ts) background using CRISPR/Cas9 gene editing. Notably, ptr-6[W701*] robustly rescued the embryonic lethality and permeability defects caused by fasn-1 loss-of-function. Taken together, our findings expand the genetic regulatory network of fatty acid synthase during early embryogenesis and highlight ptr-6 and Hedgehog-like signaling pathway as potential genetic modifiers of fatty acid synthase-associated developmental and metabolic disorders.</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":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148382036","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":"Mistranslation protects against lifespan reduction due to mating in Drosophila melanogaster females.","authors":"Luana Branco, William Yeung, Joshua R Isaacson, Amanda J Moehring","doi":"10.1093/g3journal/jkag216","DOIUrl":"10.1093/g3journal/jkag216","url":null,"abstract":"<p><p>Accurate translation of genes into proteins is critical to organism fitness, and errors in this process are usually detrimental and cause proteotoxic stress. Mistranslation occurs when the amino acid that is incorporated into the nascent polypeptide chain does not match what is dictated by the genetic code. Valine-to-serine (V→S) and threonine-to-serine (T→S) mistranslating models of the fruit fly Drosophila melanogaster have demonstrated a surprising, sex-specific increase in virgin female longevity. We predict that the added stressor of reproduction would eliminate this mistranslation-induced lifespan increase since females prioritize reproductive tissues over somatic tissues, and proteotoxic stress would therefore lead to higher protein damage and cell death in the soma of mated females. We measured the impact of reproduction on V→S and T→S mistranslating D. melanogaster by measuring longevity, egg laying, and fecundity. Counter to our prediction, both V→S and T→S mistranslation led to a sex-specific increase in mated female longevity compared with nonmistranslating controls. Additionally, the risk of death decreased for mated females with mistranslation, beyond the pure additive benefits of mistranslation alone. These effects could not be explained by reduced egg laying or fertilization rates in mistranslating females. Thus, we find that the added proteotoxic stress caused by mistranslation does not exacerbate the detrimental effects of reproduction and instead can ameliorate lifespan decreases due to female reproduction.</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/PMC13643807/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148711866","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":"Rescue of a decapentaplegic hypomorphic wing growth phenotype by expression of the signaling ligands Hedgehog, Semaphorin a1, and Wnt homolog 2 in Drosophila melanogaster.","authors":"Anthony Percival-Smith, Cooper Brabrook","doi":"10.1093/g3journal/jkag202","DOIUrl":"10.1093/g3journal/jkag202","url":null,"abstract":"<p><p>An expectation of a hypothesis that proposes cell-to-cell signaling pathways are redundant due to the redundancy of pathway terminal transcription factors (TFs) was tested by screening 35 signaling ligands for rescue of a decapentaplegic (dpp) hypomorphic wing growth phenotype. Three examples of partial rescue were identified: Hedgehog (HH), Semaphorin 1a (SEMA1A), and Wnt ortholog 2 (WNT2). HH overexpression with dppGAL4 may increase the expression of DPP from the hypomorphic dpp alleles. However, SEMA1A and WNT2 did not phenocopy the ectopic expression of HH or DPP, and neither SEMA1A nor WNT2 were required for wing growth, suggesting substitution of DPP for restoration of wing growth. The WNT2 rescue was dependent on the Frizzled 4 WNT receptor excluding the possibility that WNT2 weakly binds the DPP receptor. Although examples of phenotypic nonspecificity of signaling ligand function were identified, this is an expectation, and not direct proof, of the hypothesis of TF redundancy.</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/PMC13643765/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148591188","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":"Dual roles for a chromatin insulator-H2Av axis in the DNA damage response and hematopoietic development in Drosophila.","authors":"James Ryan Simmons, Justin Kemp, Mariano Labrador","doi":"10.1093/g3journal/jkag185","DOIUrl":"10.1093/g3journal/jkag185","url":null,"abstract":"<p><p>Chromatin insulator proteins regulate genome architecture and maintain genome integrity, yet how insulator function intersects with the DNA damage response and developmental gene regulation remains poorly understood. Here we show that the Drosophila insulator protein Suppressor of Hairy wing [Su(Hw)] and the histone variant H2Av form a functional axis that operates in both contexts. In response to UV and X-ray irradiation, Su(Hw) enrichment at insulator sites increases and Su(Hw) is required for phosphorylation of H2Av, the Drosophila equivalent of vertebrate H2AX, establishing Su(Hw) as a component of the DNA damage response. Simultaneous mutation of the damage-sensing kinases ATR and ATM disrupts normal Su(Hw) chromatin binding dynamics, further linking insulator activity to the DNA damage signaling network. Beyond genome integrity, Su(Hw) and H2Av interact genetically to control larval hematopoiesis: mutation of His2Av produces melanotic masses and reduced lymph glands, phenotypes that are suppressed in a Su(Hw) dose-dependent manner, while double mutants display supernumerary and overgrown lymph gland lobes. Together, these findings establish dual roles for a chromatin insulator-histone variant axis in which Su(Hw) and H2Av interact to regulate both the cellular response to DNA damage and the transcriptional control of lymph gland development in Drosophila.</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/PMC13643779/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790016","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":"First chromosome-scale genome of Cornus kousa K2‡.","authors":"Trinity P H Mehler, Sarah L Boggess, Marcin Nowicki, Denita Hadziabdic, DeWayne Shoemaker, Robert N Trigiano, William E Klingeman, Thomas J Molnar, Sheron A Simpson, Ramey C Youngblood, Amanda M Hulse-Kemp, Brian E Scheffler, Margaret E Staton","doi":"10.1093/g3journal/jkag229","DOIUrl":"10.1093/g3journal/jkag229","url":null,"abstract":"<p><p>Kousa dogwood (Cornus kousa Hance) is a popular flowering ornamental tree in the United States, largely due to its pest and disease tolerance. Here, we present the first chromosome-scale, diploid genome assembly of C. kousa K2, a foundational breeding parent. The final chromosome-scale genome assemblies are 1602.739 Mb for Hap 1 and 1598.929 Mb for Hap 2. The complete Benchmarking Universal Single-Copy Orthologs (BUSCO) for Hap 1 and 2 were 98.8 and 98.4%, respectively. Between the 2 haplotypes, 98.97% of the genome is placed into chromosomes. 30,799 and 31,044 genes were annotated in Hap 1 and Hap 2, respectively. This annotated genome assembly for C. kousa provides insight into the genomic composition of the species and will enhance our understanding of the genetic control of traits of interest in breeding programs and the evolutionary history of the Cornus genus.</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/PMC13643784/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148790482","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":"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}