PLoS Genetics最新文献

Nuclear p62/SQSTM1 facilitates ubiquitin-independent proteasomal degradation of BMAL1. 核p62/SQSTM1促进BMAL1的泛素非依赖性蛋白酶体降解。

IF 4 2区生物学

PLoS Genetics Pub Date : 2025-07-10 DOI: 10.1371/journal.pgen.1011794

Chenliang Zhang, Quanyou Wu, Huan Zhang, RuiChen Liu, Liping Li

引用次数: 0

Experimental evolution partially restores functionality of bacterial chemotaxis network with reduced number of components. 实验进化部分恢复了细菌趋化网络的功能，减少了组成部分的数量。

IF 4 2区生物学

PLoS Genetics Pub Date : 2025-07-10 DOI: 10.1371/journal.pgen.1011784

Manika Kargeti, Irina Kalita, Sarah Hoch, Maryia Ratnikava, Wenhao Xu, Bin Ni, Ron L Dy, Remy Colin, Victor Sourjik

{"title":"Experimental evolution partially restores functionality of bacterial chemotaxis network with reduced number of components.","authors":"Manika Kargeti, Irina Kalita, Sarah Hoch, Maryia Ratnikava, Wenhao Xu, Bin Ni, Ron L Dy, Remy Colin, Victor Sourjik","doi":"10.1371/journal.pgen.1011784","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011784","url":null,"abstract":"The chemotaxis signaling pathway, which enables bacteria to follow chemical gradients in their environment, is highly conserved among motile bacteria. It is assumed that Escherichia coli contains the minimal and non-redundant set of protein activities that are necessary for bacterial chemotaxis and nearly universally conserved among bacterial chemotaxis pathways. These include stimulus sensing, signal transduction towards the flagellar motor, and adaptation-based temporal comparisons of the environment. In this study, we show that functionality of the chemotaxis signaling pathway lacking some of its proteins can be partially regained by subjecting E. coli strains to experimental evolution under selection for chemotactic spreading in porous medium. While the core signaling components are indeed essential for the pathway function, the absence of auxiliary pathway proteins required for adaptation and desensitization could be compensated by specific sets of mutations affecting the other pathway components. Further characterization of the evolved strain lacking the adaptation enzyme CheR suggested that this strain utilizes an alternative mechanism of biased drift in chemical gradients, which does not rely on short-term adaptation that is normally considered a prerequisite for bacterial chemotaxis. Although the efficiency of this alternative mechanism remains below the one that can be achieved by the original memory-based chemotaxis strategy of E. coli, it can mediate chemotaxis not only in porous medium but also in liquid. Thus, even short-term experimental evolution of microorganisms can result in the appearance of behavioral strategies that are qualitatively different from those used by parental organisms.","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 7","pages":"e1011784"},"PeriodicalIF":4.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610115","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

L-2-hydroxyglutarate regulates centromere and heterochromatin conformation in the male germline. l -2-羟戊二酸调节雄性生殖系着丝粒和异染色质构象。

IF 4 2区生物学

PLoS Genetics Pub Date : 2025-07-10 DOI: 10.1371/journal.pgen.1011785

Nina Mayorek, Miriam Schlossberg, Yousef Mansour, Nir Pillar, Ilan Stein, Fatima Mushasha, Guy Baziza Paz, Eleonora Medvedev, Zakhariya Manevitch, Julia Menzel, Elina Aizenshtein, Boris Sarvin, Nikita Sarvin, Erwin Goldberg, Bryan A Niedenberger, Christopher B Geyer, Tomer Shlomi, Michael Klutstein, Eli Pikarsky

{"title":"L-2-hydroxyglutarate regulates centromere and heterochromatin conformation in the male germline.","authors":"Nina Mayorek, Miriam Schlossberg, Yousef Mansour, Nir Pillar, Ilan Stein, Fatima Mushasha, Guy Baziza Paz, Eleonora Medvedev, Zakhariya Manevitch, Julia Menzel, Elina Aizenshtein, Boris Sarvin, Nikita Sarvin, Erwin Goldberg, Bryan A Niedenberger, Christopher B Geyer, Tomer Shlomi, Michael Klutstein, Eli Pikarsky","doi":"10.1371/journal.pgen.1011785","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011785","url":null,"abstract":"Germ cell differentiation in the male testis involves extensive phenotypic, transcriptional, and epigenetic modifications, which are essential for producing functional spermatozoa. Among all organs, the testis exhibits the highest baseline physiological levels of L-2-hydroxyglutarate (L-2HG), yet its role in male germ cell development remains unknown. Here, we reveal that L-2HG is synthesized during the pachytene and diplotene stages of meiosis by the testis-specific enzyme lactate dehydrogenase C (LDHC). Surprisingly, LDHC translocates into the nucleus, localizing along the synaptonemal complex and at centromeres. L-2HG, produced by LDHC, regulates centromere condensation and heterochromatin organization via multiple mechanisms, including chromocenter clustering, centromere and chromocenter condensation, and modulation of satellite RNA expression. These effects are rapid, specific to L-2HG, and independent of histone methylation changes. Acute depletion of L-2HG in vivo results in centromere dysfunction and activation of the spindle assembly checkpoint (SAC), suggesting the possible role of this metabolite in ensuring proper chromosome segregation.","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 7","pages":"e1011785"},"PeriodicalIF":4.0,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144610116","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

The foraging gene coordinates brain and heart networks to modulate socially cued interval timing in Drosophila. 觅食基因协调大脑和心脏网络来调节果蝇的社会提示间隔时间。

IF 4 2区生物学

PLoS Genetics Pub Date : 2025-07-08 eCollection Date: 2025-07-01 DOI: 10.1371/journal.pgen.1011752

Hongyu Miao, Wengjing Li, Yongwen Huang, Woo Jae Kim

{"title":"The foraging gene coordinates brain and heart networks to modulate socially cued interval timing in Drosophila.","authors":"Hongyu Miao, Wengjing Li, Yongwen Huang, Woo Jae Kim","doi":"10.1371/journal.pgen.1011752","DOIUrl":"10.1371/journal.pgen.1011752","url":null,"abstract":"The foraging gene (for) regulates behavioral plasticity and decision-making, influencing adaptive behaviors such as foraging, learning, and memory. In Drosophila melanogaster, we explore its role in interval timing behaviors, particularly mating duration. Two allelic variants, rover (forR) and sitter (forS), exhibit distinct effects: forR disrupts shorter mating duration (SMD) but not longer mating duration (LMD), while forS impairs LMD but not SMD. Transheterozygotes (forR/forS) disrupt both behaviors, revealing complex allelic interactions. Using single-cell RNA sequencing and knockdown experiments, we identify foraging expression in Pdfr-positive neurons and fru-positive heart cells as critical for LMD. While the gene is expressed in memory-related brain regions, its impact on LMD is mediated through peptidergic signaling and calcium dynamics in the heart. Social context-dependent calcium fluctuations, observed via CaLexA signals, are disrupted by foraging or Pdfr knockdown, impairing LMD. These findings highlight the foraging gene's role in integrating social cues with physiological states. This study demonstrates the foraging gene's pleiotropic roles in regulating interval timing through neural and non-neural mechanisms, offering insights into the genetic and environmental interplay underlying adaptive behaviors.","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 7","pages":"e1011752"},"PeriodicalIF":4.0,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12237022/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144592779","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}

引用次数: 0

Clonal interference and genomic repair during strain coexistence in the gut. 菌株在肠道内共存过程中的克隆干扰和基因组修复。

IF 4 2区生物学

PLoS Genetics Pub Date : 2025-07-07 DOI: 10.1371/journal.pgen.1011777

Nelson Frazão, Elsa Seixas, Manolo Mischler, Jorge Moura-de-Sousa, Hugo C Barreto, Isabel Gordo

{"title":"Clonal interference and genomic repair during strain coexistence in the gut.","authors":"Nelson Frazão, Elsa Seixas, Manolo Mischler, Jorge Moura-de-Sousa, Hugo C Barreto, Isabel Gordo","doi":"10.1371/journal.pgen.1011777","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011777","url":null,"abstract":"Humans and other mammals are colonized by multiple strains of Escherichia coli, but the tempo and mode of evolution of different coexisting strains, between whom horizontal gene transfer (HGT) can occur, is poorly understood. Here, we follow in real time the evolution of two phylogenetic distinct strains of E. coli that co-colonize the mouse gut with different population sizes. We find qualitative differences in evolutionary dynamics between strains within the same host. In the strain with larger population size intense clonal interference occurs and polymorphism at a neutral marker locus is maintained, while in the strain with lower population size complete selective sweeps and loss of neutral marker polymorphism occurs. Strain coexistence is also accompanied by rich dynamics of HGT from one strain to the other. Strikingly, a rare HGT event could restore a previously lost genomic region in the recipient strain. Furthermore, we detect for the first time a case of phage piracy in the gut, where a putative phage satellite, lacking essential genes for their own replication, was likely mobilized by a helper phage to transfer between bacterial hosts. Our results show that HGT is a key mechanism underlying genetic exchanges and adaptive genomic repair in the mammalian gut.","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 7","pages":"e1011777"},"PeriodicalIF":4.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585450","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Protein sequence editing defines distinct and overlapping functions of SKN-1A/Nrf1 and SKN-1C/Nrf2. 蛋白序列编辑定义了SKN-1A/Nrf1和SKN-1C/Nrf2不同且重叠的功能。

IF 4 2区生物学

PLoS Genetics Pub Date : 2025-07-07 DOI: 10.1371/journal.pgen.1011780

Briar Jochim, Irini Topalidou, Nicolas Lehrbach

{"title":"Protein sequence editing defines distinct and overlapping functions of SKN-1A/Nrf1 and SKN-1C/Nrf2.","authors":"Briar Jochim, Irini Topalidou, Nicolas Lehrbach","doi":"10.1371/journal.pgen.1011780","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011780","url":null,"abstract":"The Nrf/NFE2L family of transcription factors regulates redox balance, xenobiotic detoxification, metabolism, proteostasis, and aging. Nrf1/NFE2L1 is primarily responsible for stress-responsive upregulation of proteasome subunit genes and is essential for adaptation to proteotoxic stress. Nrf2/NFE2L2 is mainly involved in activating oxidative stress responses and promoting xenobiotic detoxification. Nrf1 and Nrf2 contain very similar DNA binding domains and can drive similar transcriptional responses. In C. elegans, a single gene, skn-1, encodes distinct protein isoforms, SKN-1A and SKN-1C, that function analogously to mammalian Nrf1 and Nrf2, respectively, and share an identical DNA binding domain. Thus, the extent to which SKN-1A/Nrf1 and SKN-1C/Nrf2 functions are distinct or overlapping has been unclear. Regulation of the proteasome by SKN-1A/Nrf1 requires post-translational conversion of N-glycosylated asparagine residues to aspartate by the PNG-1/NGLY1 peptide:N-glycanase, a process we term 'sequence editing'. Here, we reveal the consequences of sequence editing for the transcriptomic output of activated SKN-1A. We confirm that activation of proteasome subunit genes is strictly dependent on sequence editing. In addition, we find that sequence edited SKN-1A can also activate genes linked to redox homeostasis and xenobiotic detoxification that are also regulated by SKN-1C, but the extent of these genes' activation is antagonized by sequence editing. Using mutant alleles that selectively inactivate either SKN-1A or SKN-1C, we show that both isoforms promote optimal oxidative stress resistance, acting as effectors for distinct signaling pathways. These findings suggest that sequence editing governs SKN-1/Nrf functions by tuning the SKN-1A/Nrf1 regulated transcriptome.","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 7","pages":"e1011780"},"PeriodicalIF":4.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585454","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Systematically identification of survival-associated eQTLs in a Japanese kidney cancer cohort. 日本肾癌队列中生存相关的eqtl的系统鉴定

IF 4 2区生物学

PLoS Genetics Pub Date : 2025-07-07 eCollection Date: 2025-07-01 DOI: 10.1371/journal.pgen.1011770

Xiya Song, Han Jin, Xiangyu Li, Meng Yuan, Hong Yang, Yusuke Sato, Haruki Kume, Seishi Ogawa, Cheng Zhang, Adil Mardinoglu

{"title":"Systematically identification of survival-associated eQTLs in a Japanese kidney cancer cohort.","authors":"Xiya Song, Han Jin, Xiangyu Li, Meng Yuan, Hong Yang, Yusuke Sato, Haruki Kume, Seishi Ogawa, Cheng Zhang, Adil Mardinoglu","doi":"10.1371/journal.pgen.1011770","DOIUrl":"10.1371/journal.pgen.1011770","url":null,"abstract":"Background: Clear cell renal carcinoma (ccRCC) is the predominant form of kidney cancer, but the prognostic value of expression quantitative trait loci (eQTLs) remains underexplored, particularly in Asian populations.Objective: We analyzed whole-exome sequencing and RNA sequencing data from 100 Japanese ccRCC patients to identify eQTLs. Multiple Cox proportional hazard models assessed survival associations, with validation in the Cancer Genome Atlas ccRCC cohort (n = 287).Results: We identified 805 eGenes and 4,558 cis-eQTLs in the Japanese cohort. Survival analysis revealed a total of 9 eGenes significantly associated with overall survival (FDR < 0.05). Further exploratory analysis were performed using 158 eGenes and 711 eQTLs (p-value <0.05) as potential prognostic signals. Among these, 223 eQTLs regulating 54 eGenes showed consistent prognostic effects at both expression and genetic levels. Cross-population validation identified eight eQTLs regulating 11 eGenes with reproducible survival associations across ethnicities, including a missense mutation in ERV3-1 and regulatory variants near ANKRD20A7P. These variants demonstrated consistent allelic effects on both gene expression and patient survival in both cohorts.","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 7","pages":"e1011770"},"PeriodicalIF":4.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12233309/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585455","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}

引用次数: 0

Genomic organization, domain assortments, and nucleotide-binding domain diversity of NLR proteins in Sordariales fungi. Sordariales真菌NLR蛋白的基因组组织、结构域分类和核苷酸结合结构域多样性。

IF 4 2区生物学

PLoS Genetics Pub Date : 2025-07-07 DOI: 10.1371/journal.pgen.1011739

Lucas Bonometti, Florian Charriat, Noah Hensen, Silvia Miñana-Posada, Hanna Johannesson, Pierre Gladieux

{"title":"Genomic organization, domain assortments, and nucleotide-binding domain diversity of NLR proteins in Sordariales fungi.","authors":"Lucas Bonometti, Florian Charriat, Noah Hensen, Silvia Miñana-Posada, Hanna Johannesson, Pierre Gladieux","doi":"10.1371/journal.pgen.1011739","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011739","url":null,"abstract":"Fungi have NOD-Like receptors (NLRs), homologous to the innate immune receptors found in animals, plants and bacteria. Fungal NLRs are characterized by a great variability of domain organizations, but the identity of the nucleotide-binding domains, the genomic localization, and the factors associated with variation in the composition of repertoires of fungal NLRs are not yet fully understood. To better understand the variability of fungal NLR repertoires and the underlying determinants, we conducted a thorough analysis of genome data from the ascomycete order Sordariales. Using similarity searches based on hidden Markov models profiles for canonical N-terminal, nucleotide-binding, or C-terminal domains, we characterized 4613 NLRs in 82 Sordariales taxa. By examining the Helical Third section of the nucleotide-binding domains, we substantially improved their annotation. We demonstrated that fungi have NACHT domains of both NAIP-like and TLP1-like types, similar to animals. We found that the number of NLR genes was highly variable among Sordariales families, and independent of the stringency of defense mechanisms against genomic repeat elements. NLRs were organized in clusters in the majority of taxa, and the strong correlation between the number of NLRs and the number of NLR clusters suggested that organizing in clusters may contribute to repertoire diversification. Our work highlights the similarity of fungal and animal NLRs in terms of nucleotide-binding domain types, and between fungal and plant NLRs in terms of genomic organization in clusters. Our findings will aid in the comparative analysis of the patterns and processes of diversification of NLR repertoires in various lineages of fungi and between the different kingdoms and domains of life.","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 7","pages":"e1011739"},"PeriodicalIF":4.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585453","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Correction: Reduced crossover interference and increased ZMM-independent recombination in the absence of Tel1/ATM. 修正：在没有Tel1/ATM的情况下，减少了交叉干扰，增加了与zmm无关的重组。

IF 4 2区生物学

PLoS Genetics Pub Date : 2025-07-07 eCollection Date: 2025-07-01 DOI: 10.1371/journal.pgen.1011779

Carol M Anderson, Ashwini Oke, Phoebe Yam, Tangna Zhuge, Jennifer C Fung

引用次数: 0

Clu1/Clu form mitochondria-associated granules upon metabolic transitions and regulate mitochondrial protein translation via ribosome interactions. Clu1/Clu在代谢转变过程中形成线粒体相关颗粒，并通过核糖体相互作用调节线粒体蛋白翻译。

IF 4 2区生物学

PLoS Genetics Pub Date : 2025-07-07 DOI: 10.1371/journal.pgen.1011773

Leonor Miller-Fleming, Wing Hei Au, Laura Raik, Pedro Rebelo-Guiomar, Jasper Schmitz, Ha Yoon Cho, Aron Czako, Alexander J Whitworth

{"title":"Clu1/Clu form mitochondria-associated granules upon metabolic transitions and regulate mitochondrial protein translation via ribosome interactions.","authors":"Leonor Miller-Fleming, Wing Hei Au, Laura Raik, Pedro Rebelo-Guiomar, Jasper Schmitz, Ha Yoon Cho, Aron Czako, Alexander J Whitworth","doi":"10.1371/journal.pgen.1011773","DOIUrl":"https://doi.org/10.1371/journal.pgen.1011773","url":null,"abstract":"Mitochondria perform essential metabolic functions and respond rapidly to changes in metabolic and stress conditions. As the majority of mitochondrial proteins are nuclear-encoded, intricate post-transcriptional regulation is crucial to enable mitochondria to adapt to changing cellular demands. The eukaryotic Clustered mitochondria protein family has emerged as an important regulator of mitochondrial function during metabolic shifts. Here, we show that the Drosophila melanogaster and Saccharomyces cerevisiae Clu/Clu1 proteins form dynamic, membraneless, mRNA-containing granules adjacent to mitochondria in response to metabolic changes. Yeast Clu1 regulates the translation of a subset of nuclear-encoded mitochondrial proteins by interacting with their mRNAs while these are engaged in translation. We further show that Clu1 regulates translation by interacting with polysomes, independently of whether it is in a diffuse or granular state. Our results demonstrate remarkable functional conservation with other members of the Clustered mitochondria protein family and suggest that Clu/Clu1 granules isolate and concentrate ribosomes engaged in translating their mRNA targets, thus, integrating metabolic signals with the regulation of mitochondrial protein synthesis.","PeriodicalId":49007,"journal":{"name":"PLoS Genetics","volume":"21 7","pages":"e1011773"},"PeriodicalIF":4.0,"publicationDate":"2025-07-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144585451","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0