PLoS Genetics最新文献

{"title":"Dynamics of X chromosome hyper-expression and inactivation in male tissues during stick insect development.","authors":"Jelisaveta Djordjevic, Patrick Tran Van, William Toubiana, Marjorie Labédan, Zoé Dumas, Jean-Marc Aury, Corinne Cruaud, Benjamin Istace, Karine Labadie, Benjamin Noel, Darren J Parker, Tanja Schwander","doi":"10.1371/journal.pgen.1011615","DOIUrl":"10.1371/journal.pgen.1011615","url":null,"abstract":"<p><p>Differentiated sex chromosomes are frequently associated with major transcriptional changes: the evolution of dosage compensation (DC) to equalize gene expression between the sexes and the establishment of meiotic sex chromosome inactivation (MSCI). Our study investigates the mechanisms and developmental dynamics of dosage compensation and meiotic sex chromosome inactivation in the stick insect species T. poppense. Stick insects are characterized by XX/X0 sex determination, with an X chromosome that likely evolved prior to the diversification of insects over 450 Mya. We generated a chromosome-level genome assembly and analyzed gene expression from various tissues (brain, gut, antennae, leg, and reproductive tract) across developmental stages in both sexes. Our results show that complete dosage compensation is maintained in male somatic tissues throughout development, mediated by upregulation of the single X chromosome. Contrarily, in male reproductive tissues, dosage compensation is present only in the early nymphal stages. As males reach the 4th nymphal stage and adulthood, X-linked gene expression diminishes, coinciding with the onset of meiosis and MSCI, which involves classical silencing histone modifications. These findings reveal the dynamic regulation of X-linked gene expression in T. poppense, and suggest that reduced X-expression in insect testes is generally driven by MSCI rather than an absence of dosage compensation mechanisms. Our work provides critical insights into sex chromosome evolution and the complex interplay of dosage compensation and MSCI across tissues and developmental stages.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 3","pages":"e1011615"},"PeriodicalIF":4.0,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11957559/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143597946","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":"Mutations in the Staphylococcus aureus Global Regulator CodY confer tolerance to an interspecies redox-active antimicrobial.","authors":"Anthony M Martini, Sara A Alexander, Anupama Khare","doi":"10.1371/journal.pgen.1011610","DOIUrl":"10.1371/journal.pgen.1011610","url":null,"abstract":"<p><p>Bacteria often exist in multispecies communities where interactions among different species can modify individual fitness and behavior. Although many competitive interactions have been described, molecular adaptations that can counter this antagonism and preserve or increase fitness remain underexplored. Here, we characterize the adaptation of Staphylococcus aureus to pyocyanin, a redox-active interspecies antimicrobial produced by Pseudomonas aeruginosa, a co-infecting pathogen frequently isolated from wound and chronic lung infections with S. aureus. Using experimental evolution, we identified mutations in a conserved global transcriptional regulator, CodY, that confer tolerance to pyocyanin and thereby enhance survival of S. aureus. A pyocyanin tolerant CodY mutant also had a survival advantage in co-culture with P. aeruginosa, likely through tolerance specifically to pyocyanin. The transcriptional response of the CodY mutant to pyocyanin indicated a two-pronged defensive response compared to the wild type. First, the CodY mutant strongly suppressed metabolism by downregulating core metabolic pathways , especially translation-associated genes, upon exposure to pyocyanin. Metabolic suppression via ATP depletion was sufficient to provide comparable protection against pyocyanin to the wild-type strain. Second, while both the wild-type and CodY mutant strains upregulated oxidative stress response pathways upon pyocyanin exposure, the CodY mutant overexpressed multiple stress response genes compared to the wild type. We determined that catalase overexpression was critical to pyocyanin tolerance as its absence eliminated tolerance in the CodY mutant and overexpression of catalase was sufficient to impart tolerance to the wild-type strain against purified pyocyanin and in co-culture with WT P. aeruginosa. Together, these results suggest that both transcriptional responses of reduced metabolism and an increased oxidative stress response likely contribute to pyocyanin tolerance in the CodY mutant. Our data thus provide new mechanistic insight into adaptation toward interbacterial antagonism via altered regulation that facilitates multifaceted protective cellular responses.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 3","pages":"e1011610"},"PeriodicalIF":4.0,"publicationDate":"2025-03-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11918324/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143575768","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":"A novel role for Friend of GATA1 (FOG-1) in regulating cholesterol transport in murine erythropoiesis.","authors":"Ioannis-Marios Roussis, David J Pearton, Umar Niazi, Grigorios Tsaknakis, Giorgio L Papadopoulos, Riley Cook, Mansoor Saqi, Jiannis Ragoussis, John Strouboulis","doi":"10.1371/journal.pgen.1011617","DOIUrl":"10.1371/journal.pgen.1011617","url":null,"abstract":"<p><p>Friend of GATA1 (FOG-1) is an essential transcriptional co-factor of the master erythroid transcription factor GATA1. The knockout of the Zfpm1 gene, coding for FOG-1, results in early embryonic lethality due to anemia in mice, similar to the embryonic lethal phenotype of the Gata1 gene knockout. However, a detailed molecular analysis of the Zfpm1 knockout phenotype in erythropoiesis is presently incomplete. To this end, we used CRISPR/Cas9 to knockout Zfpm1 in mouse erythroleukemic (MEL) cells. Phenotypic characterization of DMSO-induced terminal erythroid differentiation showed that the Zfpm1 knockout MEL cells did not progress past the proerythroblast stage of differentiation. Expression profiling of the Zfpm1 knockout MEL cells by RNAseq showed a lack of up-regulation of erythroid-related gene expression profiles. Bioinformatic analysis highlighted cholesterol transport as a pathway affected in the Zfpm1 knockout cells. Moreover, we show that the cholesterol transporters Abca1 and Ldlr fail to be repressed during erythroid differentiation in Zfpm1 knockout cells, resulting in higher intracellular lipid levels and higher membrane fluidity. We also show that in FOG-1 knockout cells, the nuclear levels of SREBP2, a key transcriptional regulator of cholesterol biosynthesis and transport, are markedly increased. On the basis of these findings we propose that FOG-1 (and, potentially, GATA1) regulate cholesterol homeostasis during erythroid differentiation directly through the down regulation of cholesterol transport genes and indirectly, through the repression of the SREBP2 transcriptional activator of cholesterol homeostasis. Taken together, our work provides a molecular basis for understanding FOG-1 functions in erythropoiesis and reveals a novel role for FOG-1 in cholesterol transport.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 3","pages":"e1011617"},"PeriodicalIF":4.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11913303/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574605","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":"Species-specific circular RNA circDS-1 enhances adaptive evolution in Talaromyces marneffei through regulation of dimorphic transition.","authors":"Xueyan Hu, Minghao Du, Changyu Tao, Juan Wang, Yun Zhang, Yueqi Jin, Ence Yang","doi":"10.1371/journal.pgen.1011482","DOIUrl":"10.1371/journal.pgen.1011482","url":null,"abstract":"<p><p>Thermal adaptability is a crucial characteristic for mammalian pathogenic fungi that originally inhabit natural ecosystems. Thermally dimorphic fungi have evolved a unique ability to respond to host body temperature by shifting from mycelia to yeast. The high similarity of protein-coding genes between these fungi and their relatives suggests the indispensable but often overlooked roles of non-coding elements in fungal thermal adaptation. Here, we systematically delineated the landscape of full-length circRNAs in both mycelial and yeast conditions of Talaromyces marneffei, a typical thermally dimorphic fungus causing fatal Talaromycosis, by optimizing an integrative pipeline for circRNA detection utilizing next- and third-generation sequencing. We found T. marneffei circRNA demonstrated features such as shorter length, lower abundance, and circularization-biased splicing. We then identified and validated that circDS-1, independent of its parental gene, promotes the hyphae-to-yeast transition, maintains yeast morphology, and is involved in virulence regulation. Further analysis and experiments among Talaromyces confirmed that the generation of circDS-1 is driven by a T. marneffei-specific region in the flanking intron of circDS-1. Together, our findings not only provide fresh insights into the role of circRNA in fungal thermal adaptation but also reveal a novel molecular mechanism for the adaptive evolution of functional circRNAs derived from intronic mutations.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 3","pages":"e1011482"},"PeriodicalIF":4.0,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11928065/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143574608","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":"Human CD33 deficiency is associated with mild alteration of circulating white blood cell counts.","authors":"John Dominy, Jirong Bai, Christopher Koch, Maleeha Zaman Khan, Shareef Khalid, Jonathan H Chung, Madhura Panditrao, Lulu Liu, Qi Zhang, Muhammad Jahanzaib, Muhammad Rehan Mian, Muhammad Bilal Liaqat, Syed Shahzaib Raza, Riffat Sultana, Anjum Jalal, Muhammad Hamid Saeed, Shahid Abbas, Fazal Rehman Memon, Mohammad Ishaq, Kashif Saleheen, Asif Rasheed, Allan Gurtan, Danish Saleheen","doi":"10.1371/journal.pgen.1011600","DOIUrl":"10.1371/journal.pgen.1011600","url":null,"abstract":"<p><p>The single pass transmembrane protein CD33 is enriched in phagocytic and hematopoietic cell types, such as monocytes. CD33 is thought to be associated with immune cell function, susceptibility to Alzheimer's disease, and rare leukemias. Antagonism or genetic ablation of CD33 has been proposed to treat Alzheimer's disease, hematological cancers, and as a selection mechanism for enriching genetically altered blood cells. To understand the impact of chronic CD33 loss or ablation, we describe individuals who we confirmed to be missing CD33 due to germline loss of function variants. Through PheWAS-based approaches using existing whole exome biobanks and bespoke phenotyping using recall-by-genotype (RBG) studies, we show that CD33 loss of function alters circulating white blood cell counts and distributions, albeit mildly and with no overt clinical pathology. These findings indicate that chronic CD33 antagonism/ablation is likely to be safe in humans.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 3","pages":"e1011600"},"PeriodicalIF":4.0,"publicationDate":"2025-03-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11927914/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143568588","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: Canadian COVID-19 host genetics cohort replicates known severity associations.","authors":"Elika Garg, Paola Arguello-Pascualli, Olga Vishnyakova, Anat R Halevy, Samantha Yoo, Jennifer D Brooks, Shelley B Bull, France Gagnon, Celia M T Greenwood, Rayjean J Hung, Jerald F Lawless, Jordan Lerner-Ellis, Jessica K Dennis, Rohan J S Abraham, Jean-Michel Garant, Bhooma Thiruvahindrapuram, Steven J M Jones, Lisa J Strug, Andrew D Paterson, Lei Sun, Lloyd T Elliott","doi":"10.1371/journal.pgen.1011628","DOIUrl":"10.1371/journal.pgen.1011628","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1371/journal.pgen.1011192.].</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 3","pages":"e1011628"},"PeriodicalIF":4.0,"publicationDate":"2025-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11878922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143558522","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":"Functional genomics of chitin degradation by Vibrio parahaemolyticus reveals finely integrated metabolic contributions to support environmental fitness.","authors":"Landon J Getz, Oriana S Robinson, Nikhil A Thomas","doi":"10.1371/journal.pgen.1011370","DOIUrl":"10.1371/journal.pgen.1011370","url":null,"abstract":"<p><p>Vibrio species are marine prokaryotes that inhabit diverse ecological niches, colonizing abiotic and biotic surfaces. These bacteria are vital players in the global carbon cycle, assimilating billions of tonnes of chitin for carbon (and nitrogen) metabolites. Many bacterial proteins involved in the process-including chitinases, sugar transporters, and modifying enzymes-have been well studied. However, the genetic functional interplay and key drivers of Vibrio competitive survival in the presence of chitin as the dominant carbon source is not understood. To address this question, we carried out transposon sequencing (Tn-seq) to determine the genetic fitness of Vibrio parahaemolyticus mutants grown on chitin as a sole carbon source. Along with validating known Vibrio genes associated with chitin metabolism, our data newly identified vital roles for an unclassified OprD-like import chitoporin and a HexR family transcriptional regulator. Furthermore, we functionally implicated HexR in regulating multiple physiological processes involved in V. parahaemolyticus environmental survival including carbon assimilation and cell growth, biofilm formation, and cell motility. Under nutrient limiting conditions, our data revealed a requirement for HexR in filamentous cell morphology, a critical trait for V. parahaemolyticus environmental fitness. Therefore, a vital import porin and genomic regulation mediated by HexR support multiple physiological processes for Vibrio chitinolytic growth and environmental fitness.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 3","pages":"e1011370"},"PeriodicalIF":4.0,"publicationDate":"2025-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11906056/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143606421","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":"Editorial Note: PHYTOCHROME C regulation of photoperiodic flowering via PHOTOPERIOD1 is mediated by EARLY FLOWERING 3 in Brachypodium distachyon.","authors":"","doi":"10.1371/journal.pgen.1011592","DOIUrl":"10.1371/journal.pgen.1011592","url":null,"abstract":"","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 2","pages":"e1011592"},"PeriodicalIF":4.0,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11867306/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143525019","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":"Exploring adaptation routes to cold temperatures in the Saccharomyces genus.","authors":"Javier Pinto, Laura Natalia Balarezo-Cisneros, Daniela Delneri","doi":"10.1371/journal.pgen.1011199","DOIUrl":"10.1371/journal.pgen.1011199","url":null,"abstract":"<p><p>The identification of traits that affect adaptation of microbial species to external abiotic factors, such as temperature, is key for our understanding of how biodiversity originates and can be maintained in a constantly changing environment. The Saccharomyces genus, which includes eight species with different thermotolerant profiles, represent an ideal experimental platform to study the impact of adaptive alleles in different genetic backgrounds. Previous studies identified a group of adaptive genes for maintenance of growth at lower temperatures. Here, we carried out a genus-wide assessment of the role of genes partially responsible for cold-adaptation in all eight Saccharomyces species for six candidate genes. We showed that the cold tolerance trait of S. kudriavzevii and S. eubayanus is likely to have evolved from different routes, involving genes important for the conservation of redox-balance, and for the long-chain fatty acid metabolism, respectively. For several loci, temperature- and species-dependent epistasis was detected, underscoring the plasticity and complexity of the genetic interactions. The natural isolates of S. kudriavzevii, S. jurei and S. mikatae had a significantly higher expression of the genes involved in the redox balance compared to S. cerevisiae, suggesting a role at transcriptional level. To distinguish the effects of gene expression from allelic variation, we independently replaced either the promoters or the coding sequences (CDS) of two genes in four yeast species with those derived from S. kudriavzevii. Our data consistently showed a significant fitness improvement at cold temperatures in the strains carrying the S. kudriavzevii promoter, while growth was lower upon CDS swapping. These results suggest that transcriptional strength plays a bigger role in growth maintenance at cold temperatures over the CDS and supports a model of adaptation centred on stochastic tuning of the expression network.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 2","pages":"e1011199"},"PeriodicalIF":4.0,"publicationDate":"2025-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11875353/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143460130","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":"Functional constraints of wtf killer meiotic drivers.","authors":"Ananya Nidamangala Srinivasa, Samuel Campbell, Shriram Venkatesan, Nicole L Nuckolls, Jeffrey J Lange, Randal Halfmann, Sarah E Zanders","doi":"10.1371/journal.pgen.1011534","DOIUrl":"10.1371/journal.pgen.1011534","url":null,"abstract":"<p><p>Killer meiotic drivers are selfish DNA loci that sabotage the gametes that do not inherit them from a driver+/driver- heterozygote. These drivers often employ toxic proteins that target essential cellular functions to cause the destruction of driver- gametes. Identifying the mechanisms of drivers can expand our understanding of infertility and reveal novel insights about the cellular functions targeted by drivers. In this work, we explore the molecular mechanisms underlying the wtf family of killer meiotic drivers found in fission yeasts. Each wtf killer acts using a toxic Wtfpoison protein that can be neutralized by a corresponding Wtfantidote protein. The wtf genes are rapidly evolving and extremely diverse. Here we found that self-assembly of Wtfpoison proteins is broadly conserved and associated with toxicity across the gene family, despite minimal amino acid conservation. In addition, we found the toxicity of Wtfpoison assemblies can be modulated by protein tags designed to increase or decrease the extent of the Wtfpoison assembly, implicating assembly size in toxicity. We also identified a conserved, critical role for the specific co-assembly of the Wtfpoison and Wtfantidote proteins in promoting effective neutralization of Wtfpoison toxicity. Finally, we engineered wtf alleles that encode toxic Wtfpoison proteins that are not effectively neutralized by their corresponding Wtfantidote proteins. The possibility of such self-destructive alleles reveals functional constraints on wtf evolution and suggests similar alleles could be cryptic contributors to infertility in fission yeast populations. As rapidly evolving killer meiotic drivers are widespread in eukaryotes, analogous self-killing drive alleles could contribute to sporadic infertility in many lineages.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 2","pages":"e1011534"},"PeriodicalIF":4.0,"publicationDate":"2025-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11892871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143450750","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}