Nature genetics最新文献

{"title":"Pangenome analysis provides insights into legume evolution and breeding","authors":"Longfei Wang, Xinyu Jiang, Wu Jiao, Junrong Mao, Wenxue Ye, Yangrong Cao, Qingshan Chen, Qingxin Song","doi":"10.1038/s41588-025-02280-5","DOIUrl":"10.1038/s41588-025-02280-5","url":null,"abstract":"Grain legumes hold great promise for advancing sustainable agriculture. Although the evolutionary history of legume species has been investigated, the conserved mechanisms that drive adaptive evolution and govern agronomic improvement remain elusive. Here we present high-quality genome assemblies for nine widely consumed pulses, including common bean, chickpea, pea, lentil, faba bean, pigeon pea, cowpea, mung bean and hyacinth bean. Pangenome analysis reveals the expansion of distinct gene sets in cool-season and warm-season legumes, highlighting the role of gene birth and duplication in the autoregulation of nodulation. Notably, hundreds of genes undergo convergent selection during the evolution of legumes, affecting agronomic traits such as seed weight. In addition, we demonstrate that tandem amplification of transposable elements in gene-depleted regions has a crucial role in driving genome enlargement and the formation of regulatory elements in cool-season legumes. Our results provide insights into the molecular mechanisms underlying the diversification of legumes and represent a valuable resource for facilitating legume breeding. De novo long-read genome assembly for nine legume species and pangenome analysis identify genomic variations associated with environmental adaptation and domestication and highlight the role of transposable elements in genome evolution.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 8","pages":"2052-2061"},"PeriodicalIF":29.0,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144736782","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Why genomic diversity should not be framed by census alone","authors":"Manuel Corpas, Heinner Guio, Catalina Lopez-Correa, Segun Fatumo","doi":"10.1038/s41588-025-02272-5","DOIUrl":"10.1038/s41588-025-02272-5","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 8","pages":"1793-1794"},"PeriodicalIF":29.0,"publicationDate":"2025-07-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144719706","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Massively parallel immunopeptidome by DNA sequencing provides insights into cancer antigen presentation","authors":"Quanming Shi, Elana P. Simon, Cansu Cimen Bozkus, Anna Kaminska, Leandra Velazquez, Mansi Saxena, Zilin Zhang, Julia A. Belk, Shuo Wang, Nuoya Yang, Yaowen Zhang, Ashley Kwong, Yonglu Che, Robert R. Stickels, Charles R. Crain, Laura Schmidt-Hong, Cheryl F. Lichti, Gaurav D. Gaiha, Theodore L. Roth, Nina Bhardwaj, Ansuman T. Satpathy, Bingfei Yu, Howard Y. Chang","doi":"10.1038/s41588-025-02268-1","DOIUrl":"10.1038/s41588-025-02268-1","url":null,"abstract":"Human leukocyte antigens (HLAs) are encoded by the most polymorphic genes in the human genome. HLA class I alleles control antigen presentation for T cell recognition, which is pivotal for autoimmunity, infectious diseases and cancer. Current knowledge of HLA-bound peptides is limited, skewed and falls short of population-wide HLA binding profiles for high-value targets. Here we present ESCAPE-seq (enhanced single-chain antigen presentation sequencing), a massively parallel platform for comprehensive screening of class I HLA–peptide combinations for antigen presentation via deep DNA sequencing. ESCAPE-seq demonstrates programmability, high throughput, sensitivity and nominated viral and cancer epitopes. We simultaneously assessed over 75,000 peptide–HLA combinations, revealing broadly presented epitopes from oncogenic driver mutations and fusions across diverse HLA-A, HLA-B and HLA-C alleles that cover 90% of the human population. We further identified epitopes that are differentially presented, comparing oncogenic hotspot mutations versus wild type. ESCAPE-seq enables one-shot population-wide antigen presentation discovery, offering insights into HLA specificity and immune recognition of genomic mutations. ESCAPE-seq (enhanced single-chain antigen presentation sequencing) is a massively parallel platform for screening of class I HLA–peptide combinations for antigen presentation. The authors assess more than 75,000 peptide–HLA combinations, revealing presented epitopes from oncogenic driver mutations and fusions across diverse HLA-A, HLA-B and HLA-C alleles.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 8","pages":"2062-2073"},"PeriodicalIF":29.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41588-025-02268-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Large-scale genome-wide analyses of stuttering","authors":"Hannah G. Polikowsky, Alyssa C. Scartozzi, Douglas M. Shaw, Dillon G. Pruett, Hung-Hsin Chen, Lauren E. Petty, Alexander S. Petty, Emily J. Lowther, Shu-Hsien Cho, Yao Yu, 23andMe Research Team, Sahar Mozaffari, Christy L. Avery, Kathleen Mullan Harris, Reyna L. Gordon, Janet M. Beilby, Kathryn Z. Viljoen, Robin M. Jones, Chad D. Huff, Heather M. Highland, Shelly Jo Kraft, Jennifer E. Below","doi":"10.1038/s41588-025-02267-2","DOIUrl":"10.1038/s41588-025-02267-2","url":null,"abstract":"Developmental stuttering is a highly heritable, common speech condition characterized by prolongations, blocks and repetitions of speech. Although stuttering is highly heritable and enriched within families, the genetic architecture is largely understudied. We reasoned that there are both shared and distinct genetic variants impacting stuttering risk within sex and ancestry groups. To test this idea, we performed eight primary genome-wide association analyses of self-reported stuttering that were stratified by sex and ancestry, as well as secondary meta-analyses of more than one million individuals (99,776 cases and 1,023,243 controls), identifying 57 unique loci. We validated the genetic risk of self-reported stuttering in two independent datasets. We further show genetic similarity of stuttering with autism, depression and impaired musical rhythm across sexes, with follow-up analyses highlighting potentially causal relationships among these traits. Our findings provide well-powered insights into genetic factors underlying stuttering. Genome-wide analyses in over one million self-reported cases and controls identify genetic variants associated with stuttering and find genetic correlations with autism, depression and impaired musical rhythm, supporting a potential neurological basis for stuttering.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 8","pages":"1835-1847"},"PeriodicalIF":29.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41588-025-02267-2.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"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 LISTEN principles for genetic sequence data governance and database engineering","authors":"Colin J. Carlson, Monica Granados, Alexandra Phelan, Nithin Ramakrishnan, Timothée Poisot","doi":"10.1038/s41588-025-02270-7","DOIUrl":"10.1038/s41588-025-02270-7","url":null,"abstract":"Several international legal agreements include an ‘access and benefit-sharing’ (ABS) mechanism that attaches obligations to the use of genetic sequence data. These agreements are frequently subject to critique on the grounds that ABS is either fundamentally incompatible with the principles of open science, or technically challenging to implement in open scientific databases. Here, we argue that these critiques arise from a misinterpretation of the principles of open science and that both considerations can be addressed by a set of simple principles that link database engineering and governance. We introduce a checklist of six database design considerations, LISTEN: licensed, identified, supervised, transparent, enforced and non-exclusive, which can be readily adopted by both new and existing platforms participating in ABS systems. We also highlight how these principles can act in concert with familiar principles of open science, such as findable, accessible, interoperable and reusable (FAIR) data sharing. This Perspective proposes a checklist of six database design considerations, LISTEN: licensed, identified, supervised, transparent, enforced and non-exclusive, aimed at ensuring access and benefit-sharing principles in open science.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 9","pages":"2099-2105"},"PeriodicalIF":29.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715562","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Deciphering state-dependent immune features from multi-layer omics data at single-cell resolution","authors":"Ryuya Edahiro, Go Sato, Tatsuhiko Naito, Yuya Shirai, Ryunosuke Saiki, Kyuto Sonehara, Yoshihiko Tomofuji, Kenichi Yamamoto, Shinichi Namba, Noah Sasa, Genta Nagao, Qingbo S. Wang, Yugo Takahashi, Takanori Hasegawa, Toshihiro Kishikawa, Ken Suzuki, Yu-Chen Liu, Daisuke Motooka, Ayako Takuwa, Hiromu Tanaka, Shuhei Azekawa, Japan COVID-19 Task Force, Ho Namkoong, Ryuji Koike, Akinori Kimura, Seiya Imoto, Satoru Miyano, Takanori Kanai, Koichi Fukunaga, Mamoru Uemura, Takayoshi Morita, Yasuhiro Kato, Haruhiko Hirata, Yoshito Takeda, Yuichiro Doki, Hidetoshi Eguchi, Daisuke Okuzaki, Shuhei Sakakibara, Seishi Ogawa, Atsushi Kumanogoh, Yukinori Okada","doi":"10.1038/s41588-025-02266-3","DOIUrl":"10.1038/s41588-025-02266-3","url":null,"abstract":"Current molecular quantitative trait locus catalogs are mostly at bulk resolution and centered on Europeans. Here, we constructed an immune cell atlas with single-cell transcriptomics of >1.5 million peripheral blood mononuclear cells, host genetics, plasma proteomics and gut metagenomics from 235 Japanese persons, including patients with coronavirus disease 2019 (COVID-19) and healthy individuals. We mapped germline genetic effects on gene expression within immune cell types and across cell states. We elucidated cell type- and context-specific human leukocyte antigen (HLA) and genome-wide associations with T and B cell receptor repertoires. Colocalization using dynamic genetic regulation provided better understanding of genome-wide association signals. Differential gene and protein expression analyses depicted cell type- and context-specific effects of polygenic risks. Various somatic mutations including mosaic chromosomal alterations, loss of Y chromosome and mitochondrial DNA (mtDNA) heteroplasmy were projected into single-cell resolution. We identified immune features specific to somatically mutated cells. Overall, immune cells are dynamically regulated in a cell state-dependent manner characterized with multiomic profiles. A single-cell multiomic immune cell atlas from 235 Japanese, including patients with COVID-19 and healthy individuals, linked with host genetics including germline and somatic mutation, plasma proteomics and metagenomics data reveals that immune cells are dynamically regulated in a cell state-dependent manner.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 8","pages":"1905-1921"},"PeriodicalIF":29.0,"publicationDate":"2025-07-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41588-025-02266-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144715505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genomics-driven discovery of superior alleles and genes for yellow rust resistance in wheat","authors":"Jianhui Wu, Shengwei Ma, Jianqing Niu, Weihang Sun, Haitao Dong, Shusong Zheng, Jiwen Zhao, Shengjie Liu, Rui Yu, Ying Li, Jinyu Han, Yimin Wang, Tiantian Chen, Chuanliang Zhang, Wenjing Zhang, Bingyou Ding, Lu Chang, Wenbo Xue, Weijun Zheng, Chunlian Li, Dejun Han, Zhensheng Kang, Qingdong Zeng, Hong-Qing Ling","doi":"10.1038/s41588-025-02259-2","DOIUrl":"10.1038/s41588-025-02259-2","url":null,"abstract":"Yellow rust (YR), caused by Puccinia striiformis f. sp. tritici, poses a significant threat to wheat production worldwide. Breeding resistant cultivars is crucial for managing this disease. However, our understanding of the genetic mechanisms underlying YR resistance remains fragmented. To address this, we conducted a comprehensive analysis with variome data from 2,191 wheat accessions worldwide and over 47,000 YR response records across several environments and pathogen races. Through genome-wide association studies, we established a landscape of 431 YR resistance loci, providing a rich resource for resistance gene deployment. Furthermore, we cloned genes corresponding to three resistance loci, namely Yr5x (effective against several P. striiformis f. sp. tritici races), Yr6/Pm5 (conferred resistance to two pathogen species) and YrKB (TaEDR2-B; conferring broad-spectrum rust resistance without yield penalty). These findings offer valuable insights into the genetic basis of YR resistance in wheat and lay the foundation for engineering wheat with durable disease resistance. Genomic analyses of 2,191 global common wheat accessions and over 47,000 yellow rust (YR) response data points across several environments and pathogen races provide a genome-wide landscape of YR resistance genes and effective alleles.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 8","pages":"2017-2027"},"PeriodicalIF":29.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677401","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Genome assembly of two allotetraploid cotton germplasms reveals mechanisms of somatic embryogenesis and enables precise genome editing","authors":"Zhongping Xu, Guanying Wang, Xiangqian Zhu, Ruipeng Wang, Longfu Zhu, Lili Tu, Yuling Liu, Renhai Peng, Keith Lindsey, Maojun Wang, Xianlong Zhang, Shuangxia Jin","doi":"10.1038/s41588-025-02258-3","DOIUrl":"10.1038/s41588-025-02258-3","url":null,"abstract":"Somatic embryogenesis is crucial for plant genetic engineering, yet the underlying mechanisms in cotton remain poorly understood. Here we present a telomere-to-telomere assembly of Jin668 and a high-quality assembly of YZ1, two highly regenerative allotetraploid cotton germplasms. The completion of the Jin668 genome enables characterization of ~30.1 Mb of centromeric regions invaded by centromeric retrotransposon of maize and Tekay retrotransposons, an ~8.1 Mb 5S rDNA array containing 25,190 copies and a ~75.1 Mb major 45S rDNA array with 8,131 copies. Comparative analyses of regenerative and recalcitrant genotypes reveal dynamic transcriptional patterns and chromatin accessibility during the initial regeneration process. A hierarchical gene regulatory network identifies AGL15 as a contributor to regeneration. Additionally, we demonstrate that genetic variation affects sgRNA target sites, while the Jin668 genome assembly reduces the risk of off-target effects in CRISPR-based genome editing. Together, the complete Jin668 genome reveals the complexity of genomic regions and cotton regeneration, and improves the precision of genome editing. Genome assemblies of two allotetraploid cotton germplasms, Jin668 and YZ1, reveal the regulatory mechanisms underlying somatic embryogenesis and plant regeneration, and provide potential for precise genome editing in cotton.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 8","pages":"2028-2039"},"PeriodicalIF":29.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144678137","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"G-quadruplexes are promoter elements controlling nucleosome exclusion and RNA polymerase II pausing","authors":"Cyril Esnault, Amal Zine El Aabidine, Marie-Cécile Robert, Anne Cucchiarini, Talha Magat, Alexia Pigeot, Soumya Bouchouika, Encar Garcia-Oliver, Kevin Gawron, Eugénia Basyuk, Magdalena A. Karpinska, Alja Kozulic-Pirher, Yu Luo, Daniela Verga, Raphael Mourad, Ovidiu Radulescu, Jean-Louis Mergny, Edouard Bertrand, Jean-Christophe Andrau","doi":"10.1038/s41588-025-02263-6","DOIUrl":"10.1038/s41588-025-02263-6","url":null,"abstract":"Despite their central role in transcription, it has been difficult to define universal sequences associated with eukaryotic promoters. Within the chromatin context, recruitment of transcriptional machinery requires promoter opening, but how DNA elements contribute to this process is unclear. Here we show that G-quadruplex (G4) secondary DNA structures are highly enriched at mammalian promoters. G4s are located at the deepest point of nucleosome exclusion at promoters and correlate with maximum promoter activity. We found that experimental G4s exclude nucleosomes in vivo and in vitro while favouring strong positioning. At model promoters, impairing G4s affected both transcriptional activity and chromatin opening. G4 destabilization also resulted in an inactive promoter state and affected the transition to effective RNA production. Finally, G4 stabilization resulted in global reduction of proximal promoter pausing. Altogether, our data introduce G4s as bona fide promoter elements allowing nucleosome exclusion and facilitating pause–release by RNA polymerase II. This study examines the function of G-quadruplex DNA secondary structures in mammalian promoters, revealing that they represent core promoter elements contributing to gene regulation by nucleosome exclusion and by promoting RNA polymerase II pause–release.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 8","pages":"1981-1993"},"PeriodicalIF":29.0,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144677400","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-cell and spatial transcriptomics reveal mechanisms of radioresistance and immune escape in recurrent nasopharyngeal carcinoma","authors":"Rui You, Qunlun Shen, Chao Lin, Kangning Dong, Xiao Liu, Hanshi Xu, Wanming Hu, Yulong Xie, Ruoqi Xie, Xiaoyi Song, Chunliu Huang, Jinhui Wu, Tao Yu, Huifeng Li, Zining Wang, Keming Chen, Xiong Zou, Peiyu Huang, Yijun Hua, Youping Liu, Tianliang Xia, Shihua Zhang, Mingyuan Chen","doi":"10.1038/s41588-025-02253-8","DOIUrl":"10.1038/s41588-025-02253-8","url":null,"abstract":"Radiotherapy resistance and immune evasion are prominent features of recurrent nasopharyngeal carcinoma (rNPC). However, their mechanisms remain incompletely understood. Here, we conducted single-cell and spatial transcriptomics analysis of 39 tumors from 24 patients to reveal the microenvironmental differences between primary and rNPC. Specific MCAM+ cancer-associated fibroblasts are significantly enriched in rNPC, where they promote tumor radioresistance through the collagen IV–ITGA2–FAK–AKT axis. Furthermore, we found that collagen IV suppresses the infiltration of T cells, and we identified mechanisms of immune escape in rNPC. We uncovered the presence and function of CD8 ZNF683 cells in rNPC with lower cytotoxicity. The abundance of B cells and tertiary lymphoid structures significantly diminishes in rNPC. Finally, we confirmed that CD47–SIRPα commonly existed between myeloid and malignant cells in rNPC. This study provides an in-depth understanding of the mechanism of radioresistance and immune evasion in rNPC as well as highlighting critical preliminary targets for curing rNPC. Multi-omic analysis of 39 samples of treatment-naive and recurrent nasopharyngeal carcinomas highlights the importance of the tumor microenvironment in promoting radioresistance and immune escape.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"57 8","pages":"1950-1965"},"PeriodicalIF":29.0,"publicationDate":"2025-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144669923","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}