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The mechanistic and evolutionary diversity of programmed DNA elimination. 程序化DNA消除的机制和进化多样性。
IF 51.4 1区 生物学
Nature Reviews Genetics Pub Date : 2026-09-08 DOI: 10.1038/s41576-026-01004-7
Sandra Duharcourt, Laura Ross, Alexander Suh, Dmitrij Dedukh, Marie Delattre, Andreas Houben, Hanna Kokko, Radka Reifova, Julien Richard Albert, Denis Roze, Jeramiah J Smith, Jianbin Wang
{"title":"The mechanistic and evolutionary diversity of programmed DNA elimination.","authors":"Sandra Duharcourt, Laura Ross, Alexander Suh, Dmitrij Dedukh, Marie Delattre, Andreas Houben, Hanna Kokko, Radka Reifova, Julien Richard Albert, Denis Roze, Jeramiah J Smith, Jianbin Wang","doi":"10.1038/s41576-026-01004-7","DOIUrl":"10.1038/s41576-026-01004-7","url":null,"abstract":"<p><p>Beyond somatic mutations, the genetic makeup of an organism is often assumed to remain constant across all cells or nuclei within individuals. However, some organisms exhibit programmed DNA elimination (PDE), whereby specific cell lineages lose DNA segments or whole chromosomes. Building evidence indicates that PDE occurs in a wide range of eukaryotes and is linked to diverse cellular processes including gene silencing, germline differentiation, genome defence and sex determination. Here we compare PDE across broad phylogenetic groups, highlighting the mechanistic diversity, overlooked plasticity in genome integrity and the considerable gaps in our understanding of why PDE emerged recurrently and is maintained across the Tree of Life.</p>","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":" ","pages":""},"PeriodicalIF":51.4,"publicationDate":"2026-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148912613","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}
引用次数: 0
Programmable enzymes for targeted gene insertion. 用于目标基因插入的可编程酶。
IF 51.4 1区 生物学
Nature Reviews Genetics Pub Date : 2026-09-07 DOI: 10.1038/s41576-026-01002-9
George D Lampe, Rebeca T King, Samuel H Sternberg
{"title":"Programmable enzymes for targeted gene insertion.","authors":"George D Lampe, Rebeca T King, Samuel H Sternberg","doi":"10.1038/s41576-026-01002-9","DOIUrl":"https://doi.org/10.1038/s41576-026-01002-9","url":null,"abstract":"<p><p>Genome editing technologies have advanced from nuclease-based reagents that generate programmed DNA double-strand breaks, which can cause deleterious effects, to next-generation reagents that perform controlled DNA modification through double-strand break-independent mechanisms, such as base editing and prime editing. Although these approaches enable precise small-scale sequence changes, methods for programmable insertion of large DNA cargos have been limited. The ability to write entire genes or large regions into the genome could transform the treatment of genetically heterogeneous disorders, for which numerous pathogenic variants underlie a common disease and mutation-specific editing strategies are impractical. Recent advances in computational genome mining have accelerated the discovery of naturally occurring enzymes with novel biochemical and functional properties, including recombinases and transposases capable of large-scale modifications. Moreover, directed evolution, rational engineering and expanded homologue discovery are enabling the repurposing and optimization of these systems for genome engineering. Here we review recent technology development efforts that harness diverse enzymes for kilobase-scale genome engineering, with a particular focus on CRISPR-associated transposase systems.</p>","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":" ","pages":""},"PeriodicalIF":51.4,"publicationDate":"2026-09-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148906820","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}
引用次数: 0
Species-dense genomics through natural history collections 通过自然史收集的物种密集基因组学。
IF 51.4 1区 生物学
Nature Reviews Genetics Pub Date : 2026-09-02 DOI: 10.1038/s41576-026-01011-8
Paschalia Kapli, Hugh Carter, Hayley B. Free, Adam D. Leaché, Hugo J. de Boer, Tomáš Flouri, Ben Price, Gavin R. Broad, Matthew D. Clark, Mozes P. K. Blom, Karen Meusemann, Bernhard Misof, Rebecca N. Johnson, Sandra Knapp, D. Tim J. Littlewood
{"title":"Species-dense genomics through natural history collections","authors":"Paschalia Kapli,&nbsp;Hugh Carter,&nbsp;Hayley B. Free,&nbsp;Adam D. Leaché,&nbsp;Hugo J. de Boer,&nbsp;Tomáš Flouri,&nbsp;Ben Price,&nbsp;Gavin R. Broad,&nbsp;Matthew D. Clark,&nbsp;Mozes P. K. Blom,&nbsp;Karen Meusemann,&nbsp;Bernhard Misof,&nbsp;Rebecca N. Johnson,&nbsp;Sandra Knapp,&nbsp;D. Tim J. Littlewood","doi":"10.1038/s41576-026-01011-8","DOIUrl":"10.1038/s41576-026-01011-8","url":null,"abstract":"Despite sequencing advances, genomic resources remain uneven and rarely comparable by design. Turning today’s genomes into analysis-ready resources requires species-dense sampling anchored in natural history collections. Large-scale genome initiatives are transforming biodiversity genomics, but genomes remain taxonomically sparse and difficult to compare across species. Kapli and colleagues argue that natural history collections should play a central role in building species-dense genomic resources, creating the foundation needed for comparative and predictive biodiversity genomics.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"27 11","pages":"813-815"},"PeriodicalIF":51.4,"publicationDate":"2026-09-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148880908","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}
引用次数: 0
How telomere attrition protects against cancer 端粒损耗如何预防癌症。
IF 51.4 1区 生物学
Nature Reviews Genetics Pub Date : 2026-09-01 DOI: 10.1038/s41576-026-01001-w
Alexander Stuart, Bokai Zhang  (, ), Dirk Hockemeyer, Titia de Lange
{"title":"How telomere attrition protects against cancer","authors":"Alexander Stuart,&nbsp;Bokai Zhang \u0000 (,&nbsp;),&nbsp;Dirk Hockemeyer,&nbsp;Titia de Lange","doi":"10.1038/s41576-026-01001-w","DOIUrl":"10.1038/s41576-026-01001-w","url":null,"abstract":"Recent studies have shown that telomere attrition functions as a powerful and broadly effective tumour-suppressor mechanism that halts emerging cancers when telomeric DNA becomes depleted. This&nbsp;Review highlights new insights into how telomere attrition guards against cancer, including its role in limiting cell proliferation, the importance of telomere length at birth for lifelong cancer prevention, the mechanisms governing telomere length regulation and how telomerase activation enables malignant cells to bypass this barrier. In&nbsp;contrast to the popular perception that telomere shortening is harmful, the findings demonstrate that normal telomere attrition limits the risk of cancer and suggest that counteracting telomere attrition in healthy individuals (for example, by activating telomerase) could enable tumour outgrowth. Thus, such interventions are best reserved for patients with diseases caused by excessively short telomeres. The&nbsp;new data also further underscore the promise of telomerase inhibition as a broadly effective cancer therapy. In this Review, the authors discuss recent data showing that telomere attrition is a powerful tumour-suppressor mechanism that limits the development of a wide variety of human cancers.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"27 11","pages":"877-890"},"PeriodicalIF":51.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148875508","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}
引用次数: 0
Bridging precision agriculture and human medicine through comparative genetics. 通过比较遗传学连接精准农业和人类医学。
IF 51.4 1区 生物学
Nature Reviews Genetics Pub Date : 2026-08-28 DOI: 10.1038/s41576-026-01000-x
Xinfeng Liu, Bingjie Li, Lingzhao Fang
{"title":"Bridging precision agriculture and human medicine through comparative genetics.","authors":"Xinfeng Liu, Bingjie Li, Lingzhao Fang","doi":"10.1038/s41576-026-01000-x","DOIUrl":"https://doi.org/10.1038/s41576-026-01000-x","url":null,"abstract":"<p><p>Comparative genetics aims to resolve the genetic and molecular architecture of complex traits and the evolutionary constraints governing biology. Recent improvements in genome assembly, coupled with population-scale multi-omics, have generated high-resolution maps of genetic and functional variation across species. These advances have been particularly transformative for farmed animals, which have a rich reservoir of genetic diversity and provide an opportunity for systematic, full-lifespan, pan-tissue functional annotation not always possible for humans. Given the physiological similarities and shared selective environments between humans and farmed animals, a unified comparative framework that integrates human and animal omics data will enable a bidirectional flow of information and bridge the gap between statistical association and causal mechanism. This framework will be essential to accelerate the parallel development of precision agriculture and biomedicine.</p>","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":" ","pages":""},"PeriodicalIF":51.4,"publicationDate":"2026-08-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148851251","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}
引用次数: 0
Endogenous retroviruses in development and cell fate specification. 内源性逆转录病毒的发育和细胞命运规范。
IF 51.4 1区 生物学
Nature Reviews Genetics Pub Date : 2026-08-21 DOI: 10.1038/s41576-026-01009-2
Hongqing Liang
{"title":"Endogenous retroviruses in development and cell fate specification.","authors":"Hongqing Liang","doi":"10.1038/s41576-026-01009-2","DOIUrl":"https://doi.org/10.1038/s41576-026-01009-2","url":null,"abstract":"","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":" ","pages":""},"PeriodicalIF":51.4,"publicationDate":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795951","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}
引用次数: 0
Proteogenomics in human populations. 人类群体中的蛋白质基因组学。
IF 51.4 1区 生物学
Nature Reviews Genetics Pub Date : 2026-08-20 DOI: 10.1038/s41576-026-00998-4
Ranran Zhai, Anders Mälarstig, Xia Shen
{"title":"Proteogenomics in human populations.","authors":"Ranran Zhai, Anders Mälarstig, Xia Shen","doi":"10.1038/s41576-026-00998-4","DOIUrl":"https://doi.org/10.1038/s41576-026-00998-4","url":null,"abstract":"<p><p>In human population studies, proteogenomics integrates genomic and proteomic data to uncover how genetic variation shapes protein expression and function. A central focus of proteogenomics is the identification of protein quantitative trait loci (pQTL), which link genetic variants to protein abundance and offer critical insights into the molecular basis of disease. Recent years have seen pQTL studies scale rapidly, driven by advances in high-throughput proteomic platforms, the expansion of large biobank datasets and increasingly powerful cross-cohort meta-analyses, thereby greatly extending the depth, breadth and translational potential of proteogenomics. This Review highlights recent progress in proteogenomics with a focus on pQTL mapping and its downstream integration with complementary molecular data to provide insights into human disease. We also address current challenges and propose future directions to harness proteogenomics for the development of personalized therapies and improvement of health outcomes.</p>","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":" ","pages":""},"PeriodicalIF":51.4,"publicationDate":"2026-08-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795988","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}
引用次数: 0
Gene expression evolution at the dawn of RNA-seq RNA-seq时代的基因表达进化。
IF 51.4 1区 生物学
Nature Reviews Genetics Pub Date : 2026-08-18 DOI: 10.1038/s41576-026-01006-5
Camille Berthelot
{"title":"Gene expression evolution at the dawn of RNA-seq","authors":"Camille Berthelot","doi":"10.1038/s41576-026-01006-5","DOIUrl":"10.1038/s41576-026-01006-5","url":null,"abstract":"In this Journal Club, Camille Berthelot highlights a 2011 paper by Brawand et al. that used early RNA-sequencing data across several mammalian species to determine how gene expression evolves, identifying tissue-specific rates of change and signatures of adaptation.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"27 11","pages":"820-820"},"PeriodicalIF":51.4,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148796022","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}
引用次数: 0
A transcription factor hustles towards a precise target 转录因子向一个精确的目标移动。
IF 51.4 1区 生物学
Nature Reviews Genetics Pub Date : 2026-08-18 DOI: 10.1038/s41576-026-01005-6
Wulan Deng
{"title":"A transcription factor hustles towards a precise target","authors":"Wulan Deng","doi":"10.1038/s41576-026-01005-6","DOIUrl":"10.1038/s41576-026-01005-6","url":null,"abstract":"In this Journal Club, Wulan Deng highlights a landmark paper by Elf et al. that used single-molecule imaging in living bacteria to reveal how transcription factors locate specific DNA targets through a dynamic, largely stochastic search process.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"27 11","pages":"819-819"},"PeriodicalIF":51.4,"publicationDate":"2026-08-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795994","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}
引用次数: 0
Using genetics to mimic drug interactions 利用遗传学模拟药物相互作用。
IF 51.4 1区 生物学
Nature Reviews Genetics Pub Date : 2026-08-17 DOI: 10.1038/s41576-026-01003-8
Pamela Yeh
{"title":"Using genetics to mimic drug interactions","authors":"Pamela Yeh","doi":"10.1038/s41576-026-01003-8","DOIUrl":"10.1038/s41576-026-01003-8","url":null,"abstract":"In this Journal Club, Pamela Yeh recalls a landmark study by Bollenbach et al. that used genetic perturbations in Escherichia coli to uncover the mechanism underlying a classic suppressive drug interaction.","PeriodicalId":19067,"journal":{"name":"Nature Reviews Genetics","volume":"27 10","pages":"743-743"},"PeriodicalIF":51.4,"publicationDate":"2026-08-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795999","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}
引用次数: 0
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