IF 64.8 1区综合性期刊

Nature Pub Date : 2025-06-18 DOI: 10.1038/s41586-025-09171-z

V. Herklotz, M. Zhang, T. Nascimento, R. Kalfusová, J. Lunerová, J. Fuchs, D. Harpke, B. Huettel, U. Pfordt, V. Wissemann, A. Kovařík, A. Marques, C. M. Ritz

{"title":"Bimodal centromeres in pentaploid dogroses shed light on their unique meiosis","authors":"V. Herklotz, M. Zhang, T. Nascimento, R. Kalfusová, J. Lunerová, J. Fuchs, D. Harpke, B. Huettel, U. Pfordt, V. Wissemann, A. Kovařík, A. Marques, C. M. Ritz","doi":"10.1038/s41586-025-09171-z","DOIUrl":"https://doi.org/10.1038/s41586-025-09171-z","url":null,"abstract":"Sexual reproduction relies on meiotic chromosome pairing to form bivalents, a process that is complicated in polyploids owing to the presence of multiple subgenomes1. Uneven ploidy mostly results in sterility due to unbalanced chromosome pairing and segregation during meiosis. However, pentaploid dogroses (Rosa sect. Caninae; 2n = 5x = 35) achieve stable sexual reproduction through a unique mechanism: 14 chromosomes form bivalents and are transmitted biparentally, while the remaining 21 chromosomes are maternally inherited as univalents2,3. Despite being studied for over a century, the role of centromeres in this process has remained unclear. Here we analyse haplotype-resolved chromosome-level genome assemblies for three pentaploid dogroses. Subgenome phasing revealed a bivalent-forming subgenome with two highly homozygous chromosome sets and three divergent subgenomes lacking homologous partners, therefore explaining their meiotic behaviour. Comparative analyses of chromosome synteny, phylogenetic relationships and centromere composition indicate that the subgenomes originated from two divergent clades of the genus Rosa. Pollen genome analysis shows that subgenomes from different evolutionary origins form bivalents, supporting multiple origins of dogroses and highlighting variation in subgenome contributions. We reveal that bivalent-forming centromeres are enriched with ATHILA retrotransposons, contrasting with larger tandem-repeat-based centromeres mainly found in univalents. This centromere structural bimodality possibly contributes to univalent drive during female meiosis. Our findings provide insights into the unique reproductive strategies of dogroses, advancing our understanding of genome evolution, centromere diversity and meiotic mechanisms in organisms with asymmetrical inheritance systems.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"145 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319458","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Allosteric modulation and biased signalling at free fatty acid receptor 2 游离脂肪酸受体2的变构调节和偏置信号

IF 64.8 1区综合性期刊

Nature Pub Date : 2025-06-18 DOI: 10.1038/s41586-025-09186-6

Xuan Zhang, Abdul-Akim Guseinov, Laura Jenkins, Alice Valentini, Sara Marsango, Katrine Schultz-Knudsen, Trond Ulven, Elisabeth Rexen Ulven, Irina G. Tikhonova, Graeme Milligan, Cheng Zhang

{"title":"Allosteric modulation and biased signalling at free fatty acid receptor 2","authors":"Xuan Zhang, Abdul-Akim Guseinov, Laura Jenkins, Alice Valentini, Sara Marsango, Katrine Schultz-Knudsen, Trond Ulven, Elisabeth Rexen Ulven, Irina G. Tikhonova, Graeme Milligan, Cheng Zhang","doi":"10.1038/s41586-025-09186-6","DOIUrl":"https://doi.org/10.1038/s41586-025-09186-6","url":null,"abstract":"Free fatty acid receptor 2 (FFA2) is a G protein-coupled receptor (GPCR) that is a primary sensor for short-chain fatty acids produced by gut microbiota. Consequently, FFA2 is a promising drug target for immunometabolic disorders1,2,3,4. Here we report cryogenic electronic microscopy structures of FFA2 in complex with two G proteins and three distinct classes of positive allosteric modulators (PAMs), and describe noncanonical activation mechanisms that involve conserved structural features of class A GPCRs. Two PAMs disrupt the E/DRY activation microswitch5 and stabilize the conformation of intracellular loop 2 by binding to lipid-facing pockets near the cytoplasmic side of the receptor. By contrast, the third PAM promotes the separation of transmembrane helices 6 and 7 by interacting with transmembrane helix 6 at the receptor–lipid interface. Molecular dynamic simulations and mutagenesis experiments confirm these noncanonical activation mechanisms. Furthermore, we demonstrate the molecular basis for the Gi versus Gq bias, which is due to distinct conformations of intracellular loop 2 stabilized by different PAMs. These findings provide a framework for the design of tailored GPCR modulators, with implications that extend beyond FFA2 to the broader field of GPCR drug discovery.","PeriodicalId":18787,"journal":{"name":"Nature","volume":"2 1","pages":""},"PeriodicalIF":64.8,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144319584","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Bioinspired capillary force-driven super-adhesive filter 仿生毛细管力驱动超粘过滤器

IF 64.8 1区综合性期刊

Nature Pub Date : 2025-06-18 DOI: 10.1038/s41586-025-09156-y

Junyong Park, Chan Sik Moon, Ji Min Lee, Sazzadul A. Rahat, Sang Moon Kim, Jonathan T. Pham, Michael Kappl, Hans-Jürgen Butt, Sanghyuk Wooh

引用次数: 0

First ever skull from ‘Denisovan’ reveals what ancient people looked like 有史以来第一个来自丹尼索瓦人的头骨揭示了古人的长相

IF 64.8 1区综合性期刊

Nature Pub Date : 2025-06-18 DOI: 10.1038/d41586-025-01899-y

引用次数: 0

US–China trade conflict threatens biomedical collaboration 中美贸易冲突威胁生物医学合作

IF 50.5 1区综合性期刊