Pub Date : 2026-03-10DOI: 10.1038/s41588-026-02524-y
Hailin Zhang, Alex Windhorst, Elesandro Bornhofen, Zuzana Tulpova, Petr Novak, Jiri Macas, Hana Simkova, Marcin Nadzieja, Jung Min Kim, Dustin Cram, Yongguo Cao, David J. F. Konkin, Olaf Sass, Gregor Welna, Axel Himmelbach, Martin Mascher, Wolfgang Link, Soon-Jae Kwon, Tae-Jin Yang, Stig Uggerhøj Andersen, Murukarthick Jayakodi
Winter faba beans exhibit significant yield advantages over spring cultivars and hold promise for enhancing local protein production and agricultural sustainability. However, the threat of winter kill limits wider cultivation, and the genetics of faba bean winter hardiness remain unresolved. Here we develop a greatly improved faba bean reference genome and combine this with resequencing and phenotyping of winter and spring accessions to identify genetic determinants of winter hardiness. Genome-wide association analysis of frost tolerance traits identifies a major winter hardiness locus, the most strongly associated variant of which explains the vast majority of phenotypic variation and accurately differentiates between winter and spring types. Furthermore, we identify additional signals within the winter faba bean gene pool that could lead to further improvement of winter hardiness. Our work provides improved genomic resources and resolves the genetics of a key agronomic trait in a global protein crop to facilitate future breeding efforts. An improved faba bean reference genome and resequencing of winter and spring faba bean accessions identify genetic determinants of winter hardiness.
{"title":"Allelic variation at a single locus distinguishes spring and winter faba beans","authors":"Hailin Zhang, Alex Windhorst, Elesandro Bornhofen, Zuzana Tulpova, Petr Novak, Jiri Macas, Hana Simkova, Marcin Nadzieja, Jung Min Kim, Dustin Cram, Yongguo Cao, David J. F. Konkin, Olaf Sass, Gregor Welna, Axel Himmelbach, Martin Mascher, Wolfgang Link, Soon-Jae Kwon, Tae-Jin Yang, Stig Uggerhøj Andersen, Murukarthick Jayakodi","doi":"10.1038/s41588-026-02524-y","DOIUrl":"10.1038/s41588-026-02524-y","url":null,"abstract":"Winter faba beans exhibit significant yield advantages over spring cultivars and hold promise for enhancing local protein production and agricultural sustainability. However, the threat of winter kill limits wider cultivation, and the genetics of faba bean winter hardiness remain unresolved. Here we develop a greatly improved faba bean reference genome and combine this with resequencing and phenotyping of winter and spring accessions to identify genetic determinants of winter hardiness. Genome-wide association analysis of frost tolerance traits identifies a major winter hardiness locus, the most strongly associated variant of which explains the vast majority of phenotypic variation and accurately differentiates between winter and spring types. Furthermore, we identify additional signals within the winter faba bean gene pool that could lead to further improvement of winter hardiness. Our work provides improved genomic resources and resolves the genetics of a key agronomic trait in a global protein crop to facilitate future breeding efforts. An improved faba bean reference genome and resequencing of winter and spring faba bean accessions identify genetic determinants of winter hardiness.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"655-663"},"PeriodicalIF":29.0,"publicationDate":"2026-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41588-026-02524-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147381751","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}
Pub Date : 2026-03-03DOI: 10.1038/s41588-026-02515-z
Oliver R Powell,Francisco J Guzmán-Vega,Daniel S Yu,Yan L Wang,Ping Lu,Stefan T Arold,Zhiyong Liu,Mark J Banfield,Brande B H Wulff,Renjie Chen
Kinase fusion proteins (KFPs) are an emerging class of diverse intracellular plant immune receptors with critical roles in immunity in wheat (Triticum aestivum) and other members of the Triticeae. These proteins contain at least one kinase domain fused to one or more additional domains, possibly including another kinase domain. Many KFP kinase domains are predicted to possess an atypical structural motif, the extended β-finger, indicating that KFPs may operate through shared mechanisms in plant immunity despite their structural diversity. Recent research has demonstrated that KFP SR62TK from Aegilops sharonensis and RWT4 (allelic to PM24) from wheat serve as primary receptors that initiate immune signaling by recruiting a nucleotide-binding leucine-rich repeat (NLR) protein similar to sensor and helper NLR pairs. This study consolidates the current understanding of KFPs, emphasizing their structural and functional diversity, evolutionary significance and potential for engineering durable disease resistance in crops.
{"title":"The emerging role of kinase fusion proteins in cereal immunity.","authors":"Oliver R Powell,Francisco J Guzmán-Vega,Daniel S Yu,Yan L Wang,Ping Lu,Stefan T Arold,Zhiyong Liu,Mark J Banfield,Brande B H Wulff,Renjie Chen","doi":"10.1038/s41588-026-02515-z","DOIUrl":"https://doi.org/10.1038/s41588-026-02515-z","url":null,"abstract":"Kinase fusion proteins (KFPs) are an emerging class of diverse intracellular plant immune receptors with critical roles in immunity in wheat (Triticum aestivum) and other members of the Triticeae. These proteins contain at least one kinase domain fused to one or more additional domains, possibly including another kinase domain. Many KFP kinase domains are predicted to possess an atypical structural motif, the extended β-finger, indicating that KFPs may operate through shared mechanisms in plant immunity despite their structural diversity. Recent research has demonstrated that KFP SR62TK from Aegilops sharonensis and RWT4 (allelic to PM24) from wheat serve as primary receptors that initiate immune signaling by recruiting a nucleotide-binding leucine-rich repeat (NLR) protein similar to sensor and helper NLR pairs. This study consolidates the current understanding of KFPs, emphasizing their structural and functional diversity, evolutionary significance and potential for engineering durable disease resistance in crops.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"60 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2026-03-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147346268","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}
Pub Date : 2026-03-02DOI: 10.1038/s41588-026-02505-1
Muxin Gu,Woody Z Zhang,Rebecca C Fitzgerald,Alexander M Frankell,George S Vassiliou
Therapeutic advances have improved cancer outcomes, but early-stage detection remains the single most important determinant of favorable prognoses across many cancer types. Cancer genomics has yielded detailed maps of somatic mutation and methylation patterns characteristic of different cancers, enabling the development of assays to detect mutation-bearing tumor-derived DNA in tissue biopsies, blood and other body fluids at the earliest stages of disease. In parallel, it has also become clear that small clones bearing cancer-associated mutations arise commonly in histologically normal tissues, a phenomenon that becomes universal in proliferative tissues with age but leads to cancer in only a small minority of individuals. This review article outlines established strategies for early cancer detection and highlights emerging insights into the genetics of precancerous mutant clones that have led to the recent development of prognostic frameworks for identifying high-risk individuals, making it increasingly possible to intercept evolving cancer at a premalignant or early malignant stage, when interventions are most effective.
{"title":"Harnessing genomics for early cancer detection, risk stratification and prevention.","authors":"Muxin Gu,Woody Z Zhang,Rebecca C Fitzgerald,Alexander M Frankell,George S Vassiliou","doi":"10.1038/s41588-026-02505-1","DOIUrl":"https://doi.org/10.1038/s41588-026-02505-1","url":null,"abstract":"Therapeutic advances have improved cancer outcomes, but early-stage detection remains the single most important determinant of favorable prognoses across many cancer types. Cancer genomics has yielded detailed maps of somatic mutation and methylation patterns characteristic of different cancers, enabling the development of assays to detect mutation-bearing tumor-derived DNA in tissue biopsies, blood and other body fluids at the earliest stages of disease. In parallel, it has also become clear that small clones bearing cancer-associated mutations arise commonly in histologically normal tissues, a phenomenon that becomes universal in proliferative tissues with age but leads to cancer in only a small minority of individuals. This review article outlines established strategies for early cancer detection and highlights emerging insights into the genetics of precancerous mutant clones that have led to the recent development of prognostic frameworks for identifying high-risk individuals, making it increasingly possible to intercept evolving cancer at a premalignant or early malignant stage, when interventions are most effective.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"367 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2026-03-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147329216","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}
Pub Date : 2026-02-26DOI: 10.1038/s41588-026-02521-1
Mary Pat Reeve, Masahiro Kanai, Daniel B. Graham, Juha Karjalainen, Shuang Luo, Nikita Kolosov, Cameron Adams, Jarmo Ritari, Konrad J. Karczewski, Tuomo Kiiskinen, Yu Jiang, Zachary Fuller, Juha Mehtonen, Mitja I. Kurki, Zia Khan, FinnGen, Jukka Partanen, Mark I. McCarthy, Mykyta Artomov, Aarno Palotie, Tiinamaija Tuomi, Matti Pirinen, Jukka Kero, Ramnik J. Xavier, Mark J. Daly, Samuli Ripatti
The high prevalence (>5%) of autoimmune hypothyroidism (AIHT) provides a unique opportunity to dissect genetic contributions to systemic and organ-specific autoimmunity. Here we performed a genome-wide association meta-analysis of 81,718 AIHT cases in FinnGen and the UK Biobank, identifying 418 independent signals (P < 5 × 10−8). At 48 of these loci, a protein-coding variant is, or is highly correlated (r2 > 0.95) with, the lead variant, including Finnish-enriched coding variants in LAG3, ZAP70 and TG. We demonstrated that ZAP70:T155M reduces T cell activation and broadly compare large-scale scans of nonthyroid autoimmunity and thyroid-stimulating hormone levels with a Bayesian classifier to assign loci into distinct groupings, estimating that 38% are involved in general autoimmunity whereas 20% are thyroid specific. We further identified substantial antagonistic pleiotropy, with 10% of AIHT loci showing a consistent protective effect against skin cancer. The AIHT results, including numerous genes encoding checkpoint proteins, support the causal role of natural immune variation influencing cancer outcomes. Genome-wide analyses identify 418 independent associations with autoimmune hypothyroidism and classify risk loci into distinct groupings related to systemic autoimmunity and thyroid-specific dysfunction.
{"title":"Genome-wide association analyses of autoimmune hypothyroidism reveal autoimmune and thyroid-specific contributions and an inverse relationship with cancer risk","authors":"Mary Pat Reeve, Masahiro Kanai, Daniel B. Graham, Juha Karjalainen, Shuang Luo, Nikita Kolosov, Cameron Adams, Jarmo Ritari, Konrad J. Karczewski, Tuomo Kiiskinen, Yu Jiang, Zachary Fuller, Juha Mehtonen, Mitja I. Kurki, Zia Khan, FinnGen, Jukka Partanen, Mark I. McCarthy, Mykyta Artomov, Aarno Palotie, Tiinamaija Tuomi, Matti Pirinen, Jukka Kero, Ramnik J. Xavier, Mark J. Daly, Samuli Ripatti","doi":"10.1038/s41588-026-02521-1","DOIUrl":"10.1038/s41588-026-02521-1","url":null,"abstract":"The high prevalence (>5%) of autoimmune hypothyroidism (AIHT) provides a unique opportunity to dissect genetic contributions to systemic and organ-specific autoimmunity. Here we performed a genome-wide association meta-analysis of 81,718 AIHT cases in FinnGen and the UK Biobank, identifying 418 independent signals (P < 5 × 10−8). At 48 of these loci, a protein-coding variant is, or is highly correlated (r2 > 0.95) with, the lead variant, including Finnish-enriched coding variants in LAG3, ZAP70 and TG. We demonstrated that ZAP70:T155M reduces T cell activation and broadly compare large-scale scans of nonthyroid autoimmunity and thyroid-stimulating hormone levels with a Bayesian classifier to assign loci into distinct groupings, estimating that 38% are involved in general autoimmunity whereas 20% are thyroid specific. We further identified substantial antagonistic pleiotropy, with 10% of AIHT loci showing a consistent protective effect against skin cancer. The AIHT results, including numerous genes encoding checkpoint proteins, support the causal role of natural immune variation influencing cancer outcomes. Genome-wide analyses identify 418 independent associations with autoimmune hypothyroidism and classify risk loci into distinct groupings related to systemic autoimmunity and thyroid-specific dysfunction.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"550-559"},"PeriodicalIF":29.0,"publicationDate":"2026-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41588-026-02521-1.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147308465","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":"YamHub as an international platform for yam research and breeding based in Guadeloupe","authors":"Komivi Dossa, Gemma Arnau, Erick Malédon, Elie Nudol, Marie-Claire Gravillon, Christophe Perrot, Lévy Laurent, Saskia Sergeant, Youri Uneau, Marie Umber, Delisia Casi, Jean-Luc Irep, David Hammouya, Sandrine Andypain, Olivier Hubert, Yolande Chilin-Charles, Jacques Louisor, Marcus Hery, Bertrand Fouks, Denis Cornet, Hanâ Chaïr","doi":"10.1038/s41588-026-02520-2","DOIUrl":"https://doi.org/10.1038/s41588-026-02520-2","url":null,"abstract":"","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"2 1","pages":""},"PeriodicalIF":30.8,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147278975","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}
Pub Date : 2026-02-24DOI: 10.1038/s41588-026-02503-3
Noura Maziak, Yuchen Zhang, Fabian Groll, Haley E. Brown, Alla Madich, Yadwinder Kaur, Melissa M. Harrison, Jian Zhou, Juan M. Vaquerizas
How chromatin conformation relates to chromatin state remains a central challenge in genome regulation. Here we present Pico-C, a low-input Micro-C approach that enables high-resolution, temporally resolved three-dimensional genome mapping during early Drosophila embryogenesis. Contrary to a prevailing view of a disorganized genome before zygotic genome activation (ZGA), we uncover a dynamic and ordered emergence of chromatin loops during pre-ZGA nuclear cycles. Spatial autocorrelation analysis points to context-dependent regulatory influences on chromatin. Notably, inhibition of transcriptional elongation has site-specific effects, retaining some early loops while weakening insulation at active promoters, suggesting distinct regulatory dependencies. Machine learning models trained on sequence features identify orthogonal, motif-specific contributions to architecture. Co-depletion of the pioneer factors Zelda and GAF leads to factor-specific perturbations in chromatin architecture, further highlighting a modular regulatory logic in genome establishment. Together, our findings reveal that early genome organization is orchestrated by an interplay of overlapping yet separable regulatory inputs. Pico-C, a low-input Micro-C approach, reveals that dynamic three-dimensional genome folding precedes zygotic genome activation in Drosophila.
{"title":"Three-dimensional genome reorganization foreshadows zygotic genome activation in Drosophila","authors":"Noura Maziak, Yuchen Zhang, Fabian Groll, Haley E. Brown, Alla Madich, Yadwinder Kaur, Melissa M. Harrison, Jian Zhou, Juan M. Vaquerizas","doi":"10.1038/s41588-026-02503-3","DOIUrl":"10.1038/s41588-026-02503-3","url":null,"abstract":"How chromatin conformation relates to chromatin state remains a central challenge in genome regulation. Here we present Pico-C, a low-input Micro-C approach that enables high-resolution, temporally resolved three-dimensional genome mapping during early Drosophila embryogenesis. Contrary to a prevailing view of a disorganized genome before zygotic genome activation (ZGA), we uncover a dynamic and ordered emergence of chromatin loops during pre-ZGA nuclear cycles. Spatial autocorrelation analysis points to context-dependent regulatory influences on chromatin. Notably, inhibition of transcriptional elongation has site-specific effects, retaining some early loops while weakening insulation at active promoters, suggesting distinct regulatory dependencies. Machine learning models trained on sequence features identify orthogonal, motif-specific contributions to architecture. Co-depletion of the pioneer factors Zelda and GAF leads to factor-specific perturbations in chromatin architecture, further highlighting a modular regulatory logic in genome establishment. Together, our findings reveal that early genome organization is orchestrated by an interplay of overlapping yet separable regulatory inputs. Pico-C, a low-input Micro-C approach, reveals that dynamic three-dimensional genome folding precedes zygotic genome activation in Drosophila.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"607-617"},"PeriodicalIF":29.0,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41588-026-02503-3.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147278973","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}
Pub Date : 2026-02-24DOI: 10.1038/s41588-026-02510-4
We constructed a super pangenome for the tomato, incorporating 20 newly assembled telomere-to-telomere (T2T) genomes and 27 previously published genomes. This comprehensive, genus-wide resource enables insight into tomato pan-centromere diversity and evolution, provides a catalog of structural variants and molecular markers linked to salinity tolerance, and led to the discovery of an immune receptor that confers resistance to fungal infection.
{"title":"Harnessing wild relative diversity for engineering tomato resilience","authors":"","doi":"10.1038/s41588-026-02510-4","DOIUrl":"10.1038/s41588-026-02510-4","url":null,"abstract":"We constructed a super pangenome for the tomato, incorporating 20 newly assembled telomere-to-telomere (T2T) genomes and 27 previously published genomes. This comprehensive, genus-wide resource enables insight into tomato pan-centromere diversity and evolution, provides a catalog of structural variants and molecular markers linked to salinity tolerance, and led to the discovery of an immune receptor that confers resistance to fungal infection.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"479-480"},"PeriodicalIF":29.0,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147278974","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}
Pub Date : 2026-02-24DOI: 10.1038/s41588-026-02519-9
Viviana I. Risca
In this issue, Jiang et al. introduce a proteomic method called LoopID and show that JMJD2 demethylases have a non-catalytic role in promoting enhancer–promoter looping in mouse embryonic stem cells. This function is mediated by their intrinsically disordered domains, suggesting a condensate-based mechanism.
{"title":"Chromatin loop proteomics finds a non-catalytic function for a histone demethylase","authors":"Viviana I. Risca","doi":"10.1038/s41588-026-02519-9","DOIUrl":"10.1038/s41588-026-02519-9","url":null,"abstract":"In this issue, Jiang et al. introduce a proteomic method called LoopID and show that JMJD2 demethylases have a non-catalytic role in promoting enhancer–promoter looping in mouse embryonic stem cells. This function is mediated by their intrinsically disordered domains, suggesting a condensate-based mechanism.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"473-474"},"PeriodicalIF":29.0,"publicationDate":"2026-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147278976","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}
Pub Date : 2026-02-20DOI: 10.1038/s41588-025-02498-3
Juliette Davis, Diana Voicu, Urvashi Chitnavis, Jeremi Jaksina, Michael Imbeault
KRAB zinc-finger proteins (KZFPs) are the most abundant family of DNA-binding proteins in humans and primarily induce the epigenetic silencing of transposable elements. While KZFPs use this ability to control the transposition potential of transposable elements, they can also act as epigenetic switches that gate transposable element-derived cis-regulatory modules in a cell context-specific manner. In this way, they participate in the domestication of mobile elements, expanding their ability to establish complex gene regulatory networks. In this Perspective, we discuss emerging evidence that mutations in KZFP genes can explain human disorders and that there is a need to understand the effect of mutations in their transposable element targets. We argue that increased focus on this large yet historically understudied family will greatly contribute to addressing gaps in our understanding of cell lineage specification during development, human phenotypes and related pathologies. This Perspective explores the co-evolution of transposable elements and KRAB zinc-finger proteins in relation to their integration into human gene regulatory networks, highlighting their potential effect on human phenotypes and disease.
{"title":"The role of KRAB zinc-finger proteins in expanding the domestication potential of transposable elements","authors":"Juliette Davis, Diana Voicu, Urvashi Chitnavis, Jeremi Jaksina, Michael Imbeault","doi":"10.1038/s41588-025-02498-3","DOIUrl":"10.1038/s41588-025-02498-3","url":null,"abstract":"KRAB zinc-finger proteins (KZFPs) are the most abundant family of DNA-binding proteins in humans and primarily induce the epigenetic silencing of transposable elements. While KZFPs use this ability to control the transposition potential of transposable elements, they can also act as epigenetic switches that gate transposable element-derived cis-regulatory modules in a cell context-specific manner. In this way, they participate in the domestication of mobile elements, expanding their ability to establish complex gene regulatory networks. In this Perspective, we discuss emerging evidence that mutations in KZFP genes can explain human disorders and that there is a need to understand the effect of mutations in their transposable element targets. We argue that increased focus on this large yet historically understudied family will greatly contribute to addressing gaps in our understanding of cell lineage specification during development, human phenotypes and related pathologies. This Perspective explores the co-evolution of transposable elements and KRAB zinc-finger proteins in relation to their integration into human gene regulatory networks, highlighting their potential effect on human phenotypes and disease.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"492-502"},"PeriodicalIF":29.0,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146259061","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}
Tomato (Solanum lycopersicum), one of the world’s most valuable vegetable crops, has suffered from diminished genetic diversity and stress resistance. Wild tomatoes serve as an invaluable genetic reservoir, yet their potential for stress resilience remains largely unexploited in tomato breeding. Here we report a genus-wide super-pangenome across 16 tomato species by integrating 20 telomere-to-telomere genomes and 27 published chromosome-scale genomes. Genus-wide population analysis demonstrates broad genetic diversity with limited gene flows among principal clades. Pan-centromere analysis reveals a diverse landscape and dynamic evolution of the mysterious tomato centromeres involving rapid diversification, satellite emergence and repositioning. A comprehensive catalog of structural variants uncovers extensive rearrangements, especially from wild tomatoes, and discovers key molecular markers associated with salinity resistance. Structural-variant-based genome-wide association studies identified a leucine-rich repeat receptor gene SlGMAK conferring gray mold resistance. Our telomere-to-telomere super-pangenome will accelerate exploiting the untapped potential of wild relatives to improve modern tomatoes for stress resilience. A genus-wide super-pangenome across 16 tomato species generated by integrating 20 telomere-to-telomere genome assemblies and 27 published genomes identifies structural variants associated with salinity or disease resistance for molecular breeding.
{"title":"A tomato telomere-to-telomere super-pangenome empowers stress resilience breeding","authors":"Chunmei Shi, Shaoying Chen, Jingxuan Wang, Weikai Chen, Congying Sun, Qiang Guo, Shenhao Liao, Huan Wang, Yupei Mu, Xin Shu, Dian Meng, Jiaojiao Zhao, Liepeng Dong, Lihua Zhao, Shuguo Hou, Li Guo, Changxian Yang","doi":"10.1038/s41588-026-02508-y","DOIUrl":"10.1038/s41588-026-02508-y","url":null,"abstract":"Tomato (Solanum lycopersicum), one of the world’s most valuable vegetable crops, has suffered from diminished genetic diversity and stress resistance. Wild tomatoes serve as an invaluable genetic reservoir, yet their potential for stress resilience remains largely unexploited in tomato breeding. Here we report a genus-wide super-pangenome across 16 tomato species by integrating 20 telomere-to-telomere genomes and 27 published chromosome-scale genomes. Genus-wide population analysis demonstrates broad genetic diversity with limited gene flows among principal clades. Pan-centromere analysis reveals a diverse landscape and dynamic evolution of the mysterious tomato centromeres involving rapid diversification, satellite emergence and repositioning. A comprehensive catalog of structural variants uncovers extensive rearrangements, especially from wild tomatoes, and discovers key molecular markers associated with salinity resistance. Structural-variant-based genome-wide association studies identified a leucine-rich repeat receptor gene SlGMAK conferring gray mold resistance. Our telomere-to-telomere super-pangenome will accelerate exploiting the untapped potential of wild relatives to improve modern tomatoes for stress resilience. A genus-wide super-pangenome across 16 tomato species generated by integrating 20 telomere-to-telomere genome assemblies and 27 published genomes identifies structural variants associated with salinity or disease resistance for molecular breeding.","PeriodicalId":18985,"journal":{"name":"Nature genetics","volume":"58 3","pages":"630-642"},"PeriodicalIF":29.0,"publicationDate":"2026-02-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146210319","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}
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