PLoS Genetics最新文献

{"title":"Genomic constraint and hypervariability correlate with fitness effects in elite tetraploid potato breeding material.","authors":"Trine Aalborg, Zihui Ding, Yaoyao Wu, Elsa Sverrisdóttir, Kåre Lehmann Nielsen, Guillaume P Ramstein","doi":"10.1371/journal.pgen.1012271","DOIUrl":"10.1371/journal.pgen.1012271","url":null,"abstract":"<p><p>Tetraploid potato is the most important vegetable food crop in the world. However, genetic gains from modern breeding efforts have been limited due to tetrasomic inheritance, the accumulation of deleterious mutations during domestication, and subsequent clonal propagation during modern breeding. In this study, we analyzed previously identified evolutionarily constrained genomic regions in the potato genome relative to a breeding panel of tetraploid potato clones derived from elite cultivars (the MASPOT panel). We demonstrate a significant association between derived allele frequency (DAF) and both positive (constrained) and negative (excess of substitutions relative to neutrality, i.e., hypervariable) nucleotide conservation scores (GERP scores) in the breeding panel, indicating that negative GERP scores can annotate sites affected by positive selection or other non-neutral processes affecting population allele frequency. The deep phylogeny approach can be leveraged to alleviate inbreeding in potatoes through the qualification of causative alleles in tetraploids, offering a valuable resource for potato genetic improvement by molecular breeding. Estimates of genetic load within the tetraploid clones reveal that heterozygous loads vastly exceed homozygous loads for deleterious alleles, consistent with masking of recessive mutations. Deleterious load was significantly correlated with several trait phenotypes but did not improve prediction accuracy of any traits in the tetraploid panel. This could be due to the increased complexity of tetrasomic inheritance, including more effective load complementation, and/or a higher proportion of heterozygosity in tetraploid compared to diploid potato. Intriguingly, the hypervariable load correlated significantly with several phenotypes and improved genomic prediction accuracy of yield by 5% relative to a negative control (permuted loads). This indicates that the inferred hypervariable sites from Solanaceae evolutionary information may contain genetic information relevant for breeding, and that, in contrast to current practice, it is relevant to include and further explore sites with negative GERP scores in general.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 8","pages":"e1012271"},"PeriodicalIF":3.9,"publicationDate":"2026-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13492815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148714314","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Integrating short-read and long-read single-cell transcriptomics of pig pituitary reveals mechanisms of high-altitude hypoxia adaptation.","authors":"Hai Li, Xudong Wu, Hailong Huo, Xia Zhang, Yiming Guo, Wan Lin, Feidi Wen, Zhijun Zhao, Guiying Zhao, Jinlong Huo","doi":"10.1371/journal.pgen.1012267","DOIUrl":"10.1371/journal.pgen.1012267","url":null,"abstract":"<p><p>Acting as the central endocrine hub, the pituitary gland is closely related to the mechanism of adaptation to high-altitude hypoxia. Here, by integratively combining long-read (Oxford Nanopore) and short-read (Illumina) single-cell sequencing approaches, we profiled pituitaries from Diqing Tibetan pigs, inhabiting high-altitude environments (3,200 m) and Diannan small-ear pigs from low-altitude regions (500 m), thereby generating a full-length single-cell atlas, which in turn enabled the identification of molecular mechanisms potentially underlying adaptation to high-altitude hypoxia stress. Systematically delineating pituitary structure and transcriptional dynamics, we profiled 27,339 single cells encompassing 28,932 expressed genes. Leveraging unsupervised clustering coupled with marker-based annotation, we identified ten major cell types. Expression profiling of 20 canonical marker genes revealed pronounced cell-type-specific expression patterns, ten of which were independently validated by immunofluorescence, thus substantiating the accuracy of cell-type annotation. Gene-ontology enrichment analysis further suggested that upregulated genes were predominantly involved in oxidative metabolism and energy production, whereas downregulated genes were significantly associated with protein biosynthesis and translation processes, indicating a functional reprogramming of metabolic pathways. Moreover, comparative analyses between breeds and cell-cell communication analyses highlighted pathway shifts, including broad upregulation of the collagen family and four ligand-receptor pairs that may mediate pituitary intercellular coordination. In parallel, transcription-factor activity analysis nominated several regulators, including EBF3, DBX2, and TCF21, which may collectively contribute to altitude-associated adaptation. Finally, integrating long-read sequencing data revealed widespread transcript isoform diversity, with ~28% novel annotations, indicating considerable isoform complexity in pigs. Our findings delineate cellular heterogeneity, inferred intercellular communication networks, and transcript-isoform diversity in the porcine pituitary, thereby providing a cell-resolved resource for understanding pituitary features associated with high-altitude environments.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 8","pages":"e1012267"},"PeriodicalIF":3.9,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13472502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708237","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Lysine deficiency within a conserved lysine desert is critical for EEL-1/HUWE1 to support ubiquitin proteasome system function.","authors":"Katherine S Yanagi, Brenda J Chen, Sheikh Omar Kunjo, Irini Topalidou, Nicolas Lehrbach","doi":"10.1371/journal.pgen.1012273","DOIUrl":"10.1371/journal.pgen.1012273","url":null,"abstract":"<p><p>The ubiquitin proteasome system (UPS) is the primary mechanism for targeted protein degradation in eukaryotic cells. Dysfunction of this system is a driver of human disease and a hallmark of aging and late-onset neurodegenerative disorders. Understanding the mechanisms that ensure robust protein turnover may provide new avenues for treatment in these contexts. E3 ubiquitin ligases play critical roles in supplying ubiquitinated substrates to the proteasome, with HUWE1 being an enormous, versatile, and highly conserved member of this family. Here, we show that the C. elegans HUWE1 ortholog EEL-1 contributes to robust protein turnover, particularly during conditions that challenge the proteolytic capacity of the proteasome. We demonstrate that the ability of EEL-1/HUWE1 to safeguard protein turnover requires the HECT-type ubiquitin ligase activity, supporting a model in which EEL-1 ensures degradation via substrate ubiquitination. EEL-1 contains extensive lysine-deficient regions, found at conserved locations in its substrate-binding arena. Through unbiased mutagenesis screening and precise engineering of the EEL-1 protein, we uncover that introducing lysine residues into these regions is detrimental to UPS function and to animal physiology. Together, our findings indicate a central and evolutionarily ancient role for EEL-1/HUWE1 in maintaining optimal UPS function and support targeting this E3 for therapeutic manipulation.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 8","pages":"e1012273"},"PeriodicalIF":3.9,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13472506/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708213","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Social isolation upregulates takeout expression in female Drosophila melanogaster to promote sucrose preference.","authors":"Elisabeth A Tawa, Lisa Schneper, Katherine I Cho, Mindy Sim, Eve Schoeffler, Daniel A Notterman","doi":"10.1371/journal.pgen.1011985","DOIUrl":"10.1371/journal.pgen.1011985","url":null,"abstract":"<p><p>Previous research suggests that social isolation induces changes in gene expression that encode a starvation-like brain state and reduce sleep. However, the extent to which social isolation alters behaviors via sex-specific brain changes is unclear. Here, we use Drosophila melanogaster to explore sex differences in isolation-induced behavioral and transcriptomic changes. Male and female adult flies were isolated for seven days, and multiple behavioral sex-based differences were identified through tests of activity, motivation, aggression, and sugar preference. RNA-seq analysis also identified several candidate genes that were associated with sex differences in isolation-induced behavioral changes. Takeout (to) expression and sucrose selection were upregulated exclusively in females following social isolation. Following to knockdown in to-expressing cells, sucrose preference decreased in socially isolated females but increased in males. Overall, our results suggest that manipulating to expression influences sucrose choice in opposite directions between females and males following social isolation. It is possible that isolation-induced to overexpression in non-neuronal cells in the female head could contribute to sex differences in this behavior.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 8","pages":"e1011985"},"PeriodicalIF":3.9,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13475983/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148708207","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: Bendless is essential for PINK1-Park mediated Mitofusin degradation under mitochondrial stress caused by loss of LRPPRC.","authors":"Rajit Narayanan Cheramangalam, Tarana Anand, Priyanka Pandey, Deepa Balasubramanian, Reshmi Varghese, Neha Singhal, Sonal Nagarkar Jaiswal, Manish Jaiswal","doi":"10.1371/journal.pgen.1012268","DOIUrl":"10.1371/journal.pgen.1012268","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.pgen.1010493.].</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 8","pages":"e1012268"},"PeriodicalIF":3.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13440833/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680628","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glial cell toxicity in a Drosophila C9orf72 neurodegeneration model.","authors":"Isabel Hubbard, Josh Dubnau","doi":"10.1371/journal.pgen.1011909","DOIUrl":"10.1371/journal.pgen.1011909","url":null,"abstract":"<p><p>The most common genetic cause of both familial amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) is an expanded G4C2 repeat in the first intron of the gene C9orf72. The C9orf72 repeat expansion is bidirectionally transcribed into sense and anti-sense RNA foci, and also produces dipeptide repeats (DPRs) via a non-canonical translation mechanism known as repeat-associated (RAN) translation. Each of these components of the G4C2 repeat expansion cause neurodegenerative effects in animal models when expressed in neurons, but impacts from glial expression are more poorly understood. Here, we use glial cell type-specific expression of individual DPRs, of RNA repeat-only, or of the G4C2 repeat, that produces both DPRs and RNA repeats, to systematically investigate glial toxicity of each component. We find that as with neurons, the GR and G4C2 transgenes produce the highest degree of toxicity when expressed in glia. Each of these transgenes are capable to produce the GR DPR, which also is the most toxic factor in neurons. We demonstrate that both the GR and G4C2 transgenes cause activation of mdg4, an endogenous retrovirus (ERV). Such ERV expression is a hallmark of TDP-43 dysfunction that is commonly observed in C9orf72 patients. We find that glial expression of either the GR or the G4C2 transgene is toxic to glial cells, but such expression does not cause loss nearby neurons. However, blocking apoptotic signaling within glia that express either GR or G4C2 via expression of the p35 caspase inhibitor further exacerbates effects on lifespan and ablating such glia via expression of the proapoptotic reaper gene partially ameliorates these effects. Together, these results indicate that expression of toxic C9orf72 components in glia produces deleterious effects on lifespan, though potentially through different mechanisms than seen in TDP-43 models of ALS/FTD.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 8","pages":"e1011909"},"PeriodicalIF":3.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13480480/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680642","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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 rights and wrongs of rescaling in population genetics simulations.","authors":"Parul Johri, Fanny Pouyet, Brian Charlesworth","doi":"10.1371/journal.pgen.1012261","DOIUrl":"10.1371/journal.pgen.1012261","url":null,"abstract":"<p><p>Computer simulations of complex population genetic models are an essential tool for making sense of the large-scale datasets of multiple genome sequences from a single species that are becoming increasingly available. A widely used approach for reducing computing time is to simulate populations that are much smaller than the natural populations that they are intended to represent, by using parameters such as selection coefficients and mutation rates whose products with the population size correspond to those of the natural populations. This approach has come to be known as rescaling, and is justified by the theory of the genetics of finite populations. Recently, however, there have been criticisms of this practice, which have brought to light situations in which it can lead to erroneous conclusions. This paper reviews the theoretical basis for rescaling, and relates it to current practice in population genetics simulations. It shows that some population genetic statistics are scaleable while others are not. Additionally, it shows that there are likely to be problems with rescaling when simulating large chromosomal regions, due to the non-linear relation between the physical distance between a pair of separate nucleotide sites and the frequency of recombination between them. Other difficulties with rescaling can arise in connection with simulations of selection on complex traits, and with populations that reproduce partly by self-fertilization or asexual reproduction. A number of recommendations are made for good practice in relation to rescaling.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 8","pages":"e1012261"},"PeriodicalIF":3.9,"publicationDate":"2026-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13489532/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148680800","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Gene network analysis predicts the primary regulators of ABA-dependent transcriptional activation and repression in Populus roots.","authors":"David Cohen, Maira De Freitas Pereira, Iva Pavlović, Ondrej Novák, Marie-Béatrice Bogeat-Triboulot, Sarah Jane Cookson, Irène Hummel","doi":"10.1371/journal.pgen.1012256","DOIUrl":"10.1371/journal.pgen.1012256","url":null,"abstract":"<p><p>Abscisic acid (ABA) acts as a key signalling molecule that mediates plant responses to environmental cues as well as plant growth and development. Stress-induced and developmental changes in ABA content trigger a myriad of post-transcriptional and transcriptional events. Yet, ABA-dependent transcriptional responses are context dependent, and their temporal dynamics in roots under non-stress conditions remain poorly resolved. In this study, we characterised the hallmarks of ABA signalling and responses in the poplar root transcriptome (Populus nigra L.). We disturbed ABA homeostasis by exogenous ABA treatments, and we combined time-resolved transcriptomics with unsupervised gene network analysis to identify ABA-activated and ABA-inactivated gene co-expression modules. Considering the temporal dynamics of transcriptional events, we predicted the primary targets of the ABA signal, characterised early responding ABA-dependent processes, identified hub genes and revealed their putative functional links. We demonstrated that the properties of a master ABA-activated module induced by exogenous treatments were preserved in the transcriptome response to osmotic stress, revealing a core gene set of ABA-dependent stress responses. Our work sheds light on ABA repression of gene expression, the reprogramming of metabolism and the leaf-senescence pathway. Based on current functional knowledge and phylogenetic information, including poplar-specific features, we proposed a working model of ABA action on root transcriptome in poplar that integrates master genes, key responsive processes, and their putative regulatory architecture.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 8","pages":"e1012256"},"PeriodicalIF":3.9,"publicationDate":"2026-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13466054/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148702412","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"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: Meta-evolutionary exome analysis identifies novel type 2 diabetes mellitus genes in the UK Biobank and All of Us.","authors":"","doi":"10.1371/journal.pgen.1012265","DOIUrl":"10.1371/journal.pgen.1012265","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.pgen.1011889.].</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 8","pages":"e1012265"},"PeriodicalIF":3.9,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13432113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670975","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disruption of small RNAs and mechanistic variation in Segregation Distorter: A sperm-killing drive system in Drosophila melanogaster.","authors":"Logan T Edvalson, Xiaolu Wei, Ching-Ho Chang, Amanda M Larracuente","doi":"10.1371/journal.pgen.1012235","DOIUrl":"10.1371/journal.pgen.1012235","url":null,"abstract":"<p><p>Meiotic drivers achieve biased transmission to the next generation, often at the expense of their host. Drive is widespread and can shape the evolution of proteins, chromosome structure, and karyotypes. The sperm killer Segregation Distorter (SD) in Drosophila melanogaster is a well-studied driver but like most complex drivers, its mechanism remains elusive. SD is a multigene complex frequently associated with chromosomal inversions where the main driver locus, a truncated duplication of the gene RanGAP, kills wild-type sperm containing a satellite DNA called Responder (Rsp). Small RNAs are frequently implicated in the mechanisms of sperm killers, and we recently showed that Rsp is a source of small RNAs. Here we study the transcriptomes of two SD haplotypes and our results link Rsp expression and/or RNAs to drive. We found that Rsp-derived small RNAs are underrepresented in driving testes of only one of the SD haplotypes. We show that over-expressing Rsp is sufficient to reduce drive strength in the haplotype with downregulated Rsp but not the other. We therefore shed light on the mechanism of SD by making a connection between the target and the drive phenotype. Additionally, our data imply that different haplotypes of complex drivers, like SD, can vary in their mechanism.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"22 8","pages":"e1012235"},"PeriodicalIF":3.9,"publicationDate":"2026-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13460739/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148670963","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}