PLoS Genetics最新文献

{"title":"Single-cell consequences of X-linked meiotic drive in stalk-eyed flies.","authors":"Peter D Price, Sylvie M Parkus, Victoria J Lloyd, Ben T Alston, Sasha L Bradshaw, Sadé Bates, Margaret A Hughes, Steve Paterson, Terry Burke, Iulia Darolti, Andrew Pomiankowski, Alison E Wright","doi":"10.1371/journal.pgen.1011816","DOIUrl":"10.1371/journal.pgen.1011816","url":null,"abstract":"<p><p>Sex-linked meiotic drivers limit the inheritance of the alternate sex chromosome in the heterogametic sex, subsequently skewing the offspring sex ratio. They consequently have large impacts on genome evolution, adaptation, and the emergence and maintenance of sexually selected traits. Despite this, our understanding of their molecular basis and consequences for gametogenesis and sex chromosome regulation more broadly has focused on a handful of model organisms, primarily Drosophila and mouse, which are not representative of the broad diversity of reproductive modes and drive systems in nature. Here, we employ single-cell RNA sequencing (scRNA-seq) to investigate a sex-linked meiotic driver in the Malaysian stalk-eyed fly, Teleopsis dalmanni. First, we produce a comprehensive single-cell atlas of the male T. dalmanni gonad and identify major testis cell types. We then provide a comprehensive profile of the cellular and transcriptional landscape of the testis, providing evidence for a lack of complete meiotic sex chromosome inactivation and complex trajectory of dosage compensation. Second, by contrasting single-cell expression data between drive and standard testes, we provide insight into the consequences of a meiotic driver for the transcriptomic landscape of the testis and sex chromosome regulation. Importantly, we show that the presence of a meiotic driver does not perturb fundamental patterns of X-linked regulation. Our results provide insight into how the meiotic driver might bias its transmission to the next generation and highlight genes with perturbed expression as a potential consequence of the disruption of spermatogenesis.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 9","pages":"e1011816"},"PeriodicalIF":3.7,"publicationDate":"2025-09-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445520/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145087679","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":"Jointly representing long-range genetic similarity and spatially heterogeneous isolation-by-distance.","authors":"Vivaswat Shastry, Marco Musiani, John Novembre","doi":"10.1371/journal.pgen.1011612","DOIUrl":"10.1371/journal.pgen.1011612","url":null,"abstract":"<p><p>Isolation-by-distance patterns in genetic variation are a widespread feature of the geographic structure of genetic variation in many species, and many methods have been developed to illuminate such patterns in genetic data. However, long-range genetic similarities also exist, often as a result of rare or episodic long-range gene flow. Jointly characterizing patterns of isolation-by-distance and long-range genetic similarity in genetic data is an open data analysis challenge that, if resolved, could help produce more complete representations of the geographic structure of genetic data in any given species. Here, we present a computationally tractable method that identifies long-range genetic similarities in a background of spatially heterogeneous isolation-by-distance variation. The method uses a coalescent-based framework, and models long-range genetic similarity in terms of directional events with source fractions describing the fraction of ancestry at a location tracing back to a remote source. The method produces geographic maps annotated with inferred long-range edges, as well as maps of uncertainty in the geographic location of each source of long-range gene flow. We have implemented the method in a package called FEEMSmix (an extension to FEEMS), and validated its implementation using simulations representative of typical data applications. We also apply this method to two empirical data sets. In a data set of over 4,000 humans (Homo sapiens) across Afro-Eurasia, we recover many known signals of long-distance dispersal from recent centuries. Similarly, in a data set of over 100 gray wolves (Canis lupus) across North America, we identify several previously unknown long-range connections, some of which were attributable to recording errors in sampling locations. Therefore, beyond identifying genuine long-range dispersals, our approach also serves as a useful tool for quality control in spatial genetic studies.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 9","pages":"e1011612"},"PeriodicalIF":3.7,"publicationDate":"2025-09-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453258/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145076441","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":"Dynamic phosphorylation of Hcm1 promotes fitness in chronic stress.","authors":"Michelle M Conti, Jillian P Bail, Aurelia R Reynolds, Linnea G Budge, Mackenzie J Flynn, Rui Li, Lihua Julie Zhu, Jennifer A Benanti","doi":"10.1371/journal.pgen.1011874","DOIUrl":"10.1371/journal.pgen.1011874","url":null,"abstract":"<p><p>Cell survival depends upon the ability to adapt to changing environments. Environmental stressors trigger an acute stress response program that rewires cell physiology, downregulates proliferation genes and pauses the cell cycle until the cell adapts. After the acute response is resolved, cells resume cycling but at a reduced rate. The importance of cell cycle changes for survival in chronic stress is not clear. Here, we show that dynamic phosphorylation of the yeast cell cycle-regulatory transcription factor Hcm1 is required to maintain fitness in chronic stress. Hcm1 is activated by cyclin dependent kinase (CDK) during S-phase and is inactivated by the phosphatase calcineurin (CN) in response to stressors that signal through increases in cytosolic Ca2+. Cells expressing a constitutively active, phosphomimetic Hcm1 mutant exhibit a reduction in fitness in stress, suggesting Hcm1 inactivation promotes survival. However, a comprehensive analysis of Hcm1 phosphomutants revealed that Hcm1 activity is also important to survive stress, and that all mutants with fixed phosphorylation states are less fit in stress. Moreover, our data suggests that pulses of Hcm1 activity are necessary to maximize target gene expression in stress. These findings demonstrate that expression levels of Hcm1 target genes influence fitness in stress and suggest that the dynamic phosphorylation of cell cycle regulators plays a crucial role in promoting survival in stressful environments.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 9","pages":"e1011874"},"PeriodicalIF":3.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12453243/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070698","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":"Integrative transcriptomic analysis of Korean high-grade serous ovarian cancer.","authors":"Hyondeog Kim, Youngwook Kim, Juyeong Park, Dong-Min Shin, Ji Hyun Kim, Madhawa Gunathilake, So Young Kwon, Junyoung Shin, Chong Woo Yoo, Sang-Yoon Park, Myong Cheol Lim, Jeongseon Kim","doi":"10.1371/journal.pgen.1011660","DOIUrl":"10.1371/journal.pgen.1011660","url":null,"abstract":"<p><p>High-grade serous ovarian cancer (HGSOC) is the predominant subtype of ovarian cancer and is characterized by a high rate of relapse after platinum-based chemotherapy. Herein, we present a comprehensive analysis of 111 Korean HGSOC samples using next-generation sequencing technology to elucidate their transcriptomic landscapes. Our investigation revealed the existence of four distinct transcriptional subtypes of ovarian cancer: immunoreactive, mesenchymal, proliferative, and differentiated, which is comparable to those of TCGA HGSOC transcriptional subgroups. Each subtype exhibited unique correlation networks and their immune cell composition was computationally determined. Notably, the immunoreactive cluster displayed the highest immune score, even in the context of pan solid-cancer types, accompanied by heightened expression of CD4+ and CD8+ T cells (P < 0.05), along with notable associations with neutrophil degranulation and antigen presentation pathways (FDR < 0.01). Conversely, the differentiated cluster demonstrated immunodepleted characteristics, featuring an elevated proportion of overexpressed cancer-germline antigens. We also identified several cancer-germline HGSOC antigens that could be further investigated as potential targets for immunological intervention in cancer.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 9","pages":"e1011660"},"PeriodicalIF":3.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12494275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070723","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":"Parallel regulatory circuits orchestrate biofilm formation in response to c-di-GMP levels and growth phase.","authors":"Michael A Trebino, Giordan Kitts, James R J Haycocks, Rachel Wheat, Issac Chaudry, Jin Hwan Park, Ivan Erill, David C Grainger, Fitnat H Yildiz","doi":"10.1371/journal.pgen.1011870","DOIUrl":"10.1371/journal.pgen.1011870","url":null,"abstract":"<p><p>Biofilm formation is a highly regulated process that contributes to the environmental fitness of microorganisms, including pathogenic bacteria. The second messenger c-di-GMP is a critical regulator of biofilm formation whose cellular levels are tightly regulated by the abundance and activity of diguanylate cyclases (DGCs) and phosphodiesterases (PDEs). These enzymes synthesize and degrade c-di-GMP, respectively. The Vibrio cholerae VpvABC system encodes a DGC and is critical for biofilm formation; however, much remains unknown about its regulation. Here we demonstrate that the vpvABC system is transcriptionally regulated by c-di-GMP and the master biofilm regulators VpsT and VpsR. However, we also identify the alternative sigma factor RpoS as a positive regulator of vpvABC. RpoS is involved in the regulation of many c-di-GMP metabolism genes and plays a role in biofilm architecture, likely mediated in part through vpvC. In mature biofilms, vpvA transcription was highest near the biofilm substratum and VpsT, VpsR, and RpoS were critical for vpvABC transcription. Overall, our genetic dissection reveals the vpvABC system is regulated by two parallel circuits: a c-di-GMP sensing-circuit acting through VpsT and VpsR and a stationary growth phase circuit via RpoS. These findings underscore the multilayered regulatory mechanisms that precisely govern biofilm formation by a pathogen.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 9","pages":"e1011870"},"PeriodicalIF":3.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12456836/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070728","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":"MIG-21 interacts with Wnt and Netrin signaling in gonad migration in C. elegans.","authors":"Xin Li, Kacy Lynn Gordon","doi":"10.1371/journal.pgen.1011866","DOIUrl":"10.1371/journal.pgen.1011866","url":null,"abstract":"<p><p>The gonad of Caenorhabditis elegans hermaphrodites is a longstanding model of cell migration, stem cell niche function, and organogenesis, but it has not yet been investigated using single-cell RNA-sequencing (scRNA-seq). Using a recently published scRNA-seq dataset of adult C. elegans hermaphrodites, we identified a previously unknown regulator of the leader cell of gonad migration (the distal tip cell, or DTC). The gene mig-21 is both highly and specifically expressed in the DTC, yet has no known role in that cell. However, mig-21 regulates cell migration in other developmental contexts. Using classical genetics techniques, RNAi knockdown, and live cell imaging, we discovered that mig-21 acts synergistically with the Wnt and Netrin pathways to guide anteroposterior and dorsoventral phases of migration in the DTC at the level of signaling, not DTC cell structure. Known interactors of mig-21 in other cell types-like PTP-3C-also act with MIG-21 in DTC migration. Despite its expression in stationary adult DTCs, mig-21 does not play a role in the cessation of DTC migration but instead seems to impart continued sensitivity of the DTC to Wnt and Netrin in adulthood. This study reveals additional complexity of signaling integration between major regulators of germline stem cell niche migration, and as a proof of concept it demonstrates the utility of scRNA-seq datasets in revealing testable hypotheses about genetic networks that were masked by redundancy in traditional screening methods.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 9","pages":"e1011866"},"PeriodicalIF":3.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445740/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070763","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":"Epigenetic relay: Polycomb-directed DNA methylation in mammalian development.","authors":"Teresa Urli, Maxim V C Greenberg","doi":"10.1371/journal.pgen.1011854","DOIUrl":"10.1371/journal.pgen.1011854","url":null,"abstract":"<p><p>In mammals, repression of germline-specific gene expression is essential for preserving somatic cell identity and preventing disease. Germline gene silencing is often dependent on the presence of promoter 5-cytosine DNA methylation (5meC). Early mammalian development, however, is marked by a dramatic loss of 5meC levels genome-wide. Recent research has highlighted a specialized variant of the Polycomb Repressive Complex 1, PRC1.6, as a key regulator that maintains transient silencing of germline genes in this embryonic window. Eventually, PRC1.6 seems to stimulate the recruitment of de novo DNA methyltransferases (DNMTs), although the precise mechanisms remain to be fully elucidated. Evidence suggests a coordinated epigenetic relay, potentially involving direct protein interactions and shaping the local histone modification landscape. This review explores PRC1.6 as a central epigenetic hub that connects Polycomb repression, histone 3 lysine 9 (H3K9) methylation, and DNA methylation pathways. Unraveling this interplay will provide key insights into the mechanisms that maintain the critical barrier between the germline and the soma, essential not only for proper development but also for preserving somatic cell function and health throughout life.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 9","pages":"e1011854"},"PeriodicalIF":3.7,"publicationDate":"2025-09-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12435664/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145070762","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":"Genome-wide association study provides novel insight into the genetic architecture of severe obesity.","authors":"Mohanraj Krishnan, Mohammad Yaser Anwar, Anne E Justice, Geetha Chittoor, Hung-Hsin Chen, Rashedeh Roshani, Alyssa Scartozzi, Rachel R Dickerson, Roelof A J Smit, Michael H Preuss, Nathalie Chami, Benjamin S Hadad, Esteban J Parra, Miguel Cruz, Qin Hui, Peter W F Wilson, Yan V Sun, Xiaoyu Zhang, Gregorio V Linchangco, Sharon L R Kardia, Jessica D Faul, David R Weir, Lawrence F Bielak, Heather M Highland, Kristin L Young, Baiyu Qi, Yujie Wang, Myriam Fornage, Christopher Haiman, Iona Cheng, Ulrike Peters, Charles Kooperberg, Steven Buyske, Joseph B McCormick, Susan P Fisher-Hoch, Frida Lona-Durazo, Jesus Peralta, Jamie Gomez-Zamudio, Stephen S Rich, Kendra R Ferrier, Ethan M Lange, Christopher R Gignoux, Eimear E Kenny, Genevieve L Wojcik, Kelly Cho, Michael J Gaziano, Luc Djousse, Shuwei Liu, Dhananjay Vaidya, Renée de Mutsert, Navya S Josyula, Christopher R Bauer, Wei Zhao, Ryan W Walker, Jennifer A Smith, Leslie A Lange, Mariah C Meyer, Ching-Ti Liu, Lisa R Yanek, Miryoung Lee, Laura M Raffield, Ruth J F Loos, Penny Gordon-Larsen, Jennifer E Below, Kari E North, Mariaelisa Graff","doi":"10.1371/journal.pgen.1011842","DOIUrl":"10.1371/journal.pgen.1011842","url":null,"abstract":"<p><p>Severe obesity (SevO) is a primary driver of cardiovascular diseases (CVD), cardiometabolic diseases (CMD) and several cancers, with a disproportionate impact on marginalized populations. SevO is an understudied global health disease, limiting knowledge about its mechanisms and impacts. In genome-wide association study (GWAS) meta-analyses of the tail end of the BMI distribution (≥95th percentile BMI) and two SevO phenotypes [Obesity Class III BMI ≥ 40 kg/m2 and Obesity Class IV BMI ≥ 50 kg/m2] in 159,359 individuals across eleven ancestrally diverse population-based studies followed by replication in 480,897 individuals across six ancestrally diverse studies, we identified and replicated three novel signals in known loci of BMI [TENM2, PLCL2, ZNF184], associated with SevO traits. We confirmed a large overlap in the genetic architecture of continuous BMI and severe obesity phenotypes, suggesting little genetic heterogeneity in common variants, between obesity subgroups. Systematic analyses combining functional mapping, polygenic risk scores (PRS), phenome wide association studies (PheWAS) and environmental risk factors further reinforce shared downstream comorbidities associated with continuous measures of BMI and the importance of known lifestyle factors in interaction with genetic predisposition to SevO. Our study expands the number of SevO signals, demonstrates a strong overlap in the genetic architecture of SevO and BMI and reveals a remarkable impact of SevO on the clinical phenome, affording new opportunities for clinical prevention and mechanistic insights.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 9","pages":"e1011842"},"PeriodicalIF":3.7,"publicationDate":"2025-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12443252/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145056252","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":"Meiotic Sex Chromosome Inactivation: Conservation across the Drosophila genus.","authors":"Camila C Avelino, Carolina A Mendonca, Gabriel Goldstein, Henry Bonilla Bruno, Antonio Bernardo Carvalho, Maria D Vibranovski","doi":"10.1371/journal.pgen.1011511","DOIUrl":"10.1371/journal.pgen.1011511","url":null,"abstract":"<p><p>The inherent differences between sex chromosomes in males and females create conflicts in gene expression, driving the evolution of regulatory mechanisms such as Meiotic Sex Chromosome Inactivation (MSCI), a process that transcriptionally silences the sex chromosomes during male meiosis. In this study, we explore the evolutionary dynamics of MSCI within the Drosophila genus by analyzing transcriptomes across different stages of spermatogenesis in D. melanogaster and its progressively more distant relatives, D. simulans, D. willistoni, and D. mojavensis. Stage-enriched bulk RNA sequencing, showing a strong correlation in spermatogenic gene expression patterns among these species, revealed that MSCI dates back to the early evolution of the Drosophila genus, impacting the regulation of both coding and long non-coding RNAs. Notably, for newly evolved genes, X-linked genes show higher expression levels than autosomal genes during mitosis and meiosis, indicating that MSCI predominantly regulates older genes. In contrast, newly evolved autosomal genes exhibit a gradual increase in expression throughout spermatogenesis, reaching their peak in the post-meiotic phase. During this phase, the expression of X-linked new genes decreases, eventually aligning with that of autosomal genes. This expression pattern suggests that haploid selection plays a crucial role in the regulation of new genes, with monoallelic expression of the X chromosome providing an advantage across all stages of germline development, while autosomal gene expression gains a selective edge primarily in the post-meiotic phase. Together, these findings provide new insights into the evolution of sex chromosomes and highlight the critical role of MSCI in shaping gene expression profiles in Drosophila.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 9","pages":"e1011511"},"PeriodicalIF":3.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12425233/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041832","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":"Conservation of heat stress acclimation by the IPK2-type kinases that control the synthesis of the inositol pyrophosphate 4/6-InsP7 in land plants.","authors":"Ranjana Yadav, Guizhen Liu, Priyanshi Rana, Naga Jyothi Pullagurla, Danye Qiu, Henning J Jessen, Debabrata Laha","doi":"10.1371/journal.pgen.1011838","DOIUrl":"10.1371/journal.pgen.1011838","url":null,"abstract":"<p><p>Inositol pyrophosphates (PP-InsPs) are soluble cellular messengers that integrate environmental cues to induce adaptive responses in eukaryotes. In plants, the biological functions of various PP-InsP species are poorly understood, largely due to the absence of canonical enzymes found in other eukaryotes. The recent identification of a new PP-InsP isomer with yet unknown enantiomeric identity, 4/6-InsP7 in the eudicot Arabidopsis thaliana, further highlights the intricate PP-InsP signalling network employed by plants. Yet, the abundance of 4/6-InsP7 in land plants, the enzyme(s) responsible for its synthesis, and the physiological functions of this species are all currently unknown. In this study, we show that 4/6-InsP7 is ubiquitous in the studied land plants. Our findings demonstrate that the Arabidopsis inositol polyphosphate multikinase (IPMK) homologs, AtIPK2α and AtIPK2β phosphorylates InsP6 to generate 4/6-InsP7 as the predominant PP-InsP species in vitro. Consistent with this, AtIPK2α and AtIPK2β act redundantly to control 4/6-InsP7 production in planta. Notably, activity of these IPK2 proteins is critical for heat stress acclimation in Arabidopsis. Our parallel investigations using the liverwort Marchantia polymorpha suggest that the PP-InsP synthase activity of IPK2 and role of IPK2 in regulating the heat stress response are conserved in land plants. Furthermore, we show that the transcription activity of heat shock factor (HSF) is regulated by IPK2 proteins, providing a mechanistic framework of IPK2-controlled heat stress tolerance in land plants. Collectively, our study indicates that IPK2-type kinases have played a critical role in transducing environmental cues for biological processes during land plant evolution.</p>","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 9","pages":"e1011838"},"PeriodicalIF":3.7,"publicationDate":"2025-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12445474/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145041739","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}