Pub Date : 2025-09-03DOI: 10.1016/j.gde.2025.102397
Andres Bendesky
Recent advances in single-cell genomics are propelling a flurry of discoveries about the cellular composition of the brain and other organs across species. These discoveries, coupled with experimental manipulations, have begun to reveal how variation between species in the proportion of cell types, including the outright disappearance of some cell types and the emergence of new ones, contributes to the evolution of behavior. This review highlights these emerging findings in the context of more traditional approaches to study the evolution of behavior and discusses important outstanding questions in this field.
{"title":"Behavioral evolution by diverging cell type composition","authors":"Andres Bendesky","doi":"10.1016/j.gde.2025.102397","DOIUrl":"10.1016/j.gde.2025.102397","url":null,"abstract":"<div><div>Recent advances in single-cell genomics are propelling a flurry of discoveries about the cellular composition of the brain and other organs across species. These discoveries, coupled with experimental manipulations, have begun to reveal how variation between species in the proportion of cell types, including the outright disappearance of some cell types and the emergence of new ones, contributes to the evolution of behavior. This review highlights these emerging findings in the context of more traditional approaches to study the evolution of behavior and discusses important outstanding questions in this field.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"95 ","pages":"Article 102397"},"PeriodicalIF":3.6,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144932407","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}
Pub Date : 2025-08-30DOI: 10.1016/j.gde.2025.102396
Iain Mathieson
Ancient DNA has revolutionized our understanding of human history and clarified many aspects of human evolution on a molecular level. In this article, I describe recent efforts to translate this into descriptions of phenotypic change over time and to predict phenotypes of ancient groups and individuals. I do not discuss the more challenging problem of distinguishing between adaptive and neutral evolution and instead focus entirely on whether phenotypes and their evolution can be accurately reconstructed. I begin by describing the conceptual and technical limitations of current approaches, and then discuss efforts to reconstruct various phenotypes and the extent to which they are reliable.
{"title":"Polygenic prediction of human complex traits using ancient DNA","authors":"Iain Mathieson","doi":"10.1016/j.gde.2025.102396","DOIUrl":"10.1016/j.gde.2025.102396","url":null,"abstract":"<div><div>Ancient DNA has revolutionized our understanding of human history and clarified many aspects of human evolution on a molecular level. In this article, I describe recent efforts to translate this into descriptions of phenotypic change over time and to predict phenotypes of ancient groups and individuals. I do not discuss the more challenging problem of distinguishing between adaptive and neutral evolution and instead focus entirely on whether phenotypes and their evolution can be accurately reconstructed. I begin by describing the conceptual and technical limitations of current approaches, and then discuss efforts to reconstruct various phenotypes and the extent to which they are reliable.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"95 ","pages":"Article 102396"},"PeriodicalIF":3.6,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144916823","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}
Pub Date : 2025-08-16DOI: 10.1016/j.gde.2025.102395
Xiangyi Liu , Shuangyi Xu , Dieter Egli
Genomic instability is a significant challenge in early mammalian development and a cause for developmental failure and abnormalities, particularly in humans. Here, we review our knowledge and explore its significance of genome instability in early embryos across multiple mammalian species, including humans, rhesus macaques, mice, bovines, equines, and porcine. All these species but mice share one feature: frequent chromosomal aberrations, aneuploidy, and developmental failure. We discuss the impact of genome instability on embryonic development, the applicability of gene editing using Cas9, and potential evolutionary implications. We also explore the role of germ cell and early embryo mutations and the bottleneck effect in mammals in comparison to lower vertebrates. Understanding genome stability in mammalian embryos can contribute to our understanding of genetic variation in development and evolution.
{"title":"Genome instability in mammalian embryos implications for genome editing, development, and evolution","authors":"Xiangyi Liu , Shuangyi Xu , Dieter Egli","doi":"10.1016/j.gde.2025.102395","DOIUrl":"10.1016/j.gde.2025.102395","url":null,"abstract":"<div><div>Genomic instability is a significant challenge in early mammalian development and a cause for developmental failure and abnormalities, particularly in humans. Here, we review our knowledge and explore its significance of genome instability in early embryos across multiple mammalian species, including humans, rhesus macaques, mice, bovines, equines, and porcine. All these species but mice share one feature: frequent chromosomal aberrations, aneuploidy, and developmental failure. We discuss the impact of genome instability on embryonic development, the applicability of gene editing using Cas9, and potential evolutionary implications. We also explore the role of germ cell and early embryo mutations and the bottleneck effect in mammals in comparison to lower vertebrates. Understanding genome stability in mammalian embryos can contribute to our understanding of genetic variation in development and evolution.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"94 ","pages":"Article 102395"},"PeriodicalIF":3.6,"publicationDate":"2025-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144852349","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}
Pub Date : 2025-08-06DOI: 10.1016/j.gde.2025.102394
Saba Montazaribarforoushi , Lachlan A Jolly
Nonsense-mediated mRNA decay (NMD) is a translation-dependent mRNA decay mechanism that serves the purpose of controlling both mRNA quality and quantity. As a quality control mechanism, NMD protects organisms against the deleterious effects of mRNAs that encode premature termination codons, which arise through either transcriptional errors or genetic variation. NMD is also employed as a major regulator of physiological gene expression levels, and complete knockouts of multiple NMD genes are embryonic lethal in model organisms. The identification of genes that contribute to human Mendelian disease has now highlighted that gene variants that impact NMD function contribute to a spectrum of neurodevelopmental disorders (NDDs). Here, we capture the current landscape of NMD genes and gene variants implicated in NDDs with a focus on recent discoveries. The survey highlighted the involvement of more than half of all NMD and NMD-related genes in NDDs, representing a significant enrichment. That compromised NMD is a likely convergent pathogenic mechanism across multiple genetic causes of NDDs warrants ongoing investigation into the role of NMD in brain development.
{"title":"Genetic disruption of nonsense-mediated mRNA decay in neurodevelopmental disorders","authors":"Saba Montazaribarforoushi , Lachlan A Jolly","doi":"10.1016/j.gde.2025.102394","DOIUrl":"10.1016/j.gde.2025.102394","url":null,"abstract":"<div><div>Nonsense-mediated mRNA decay (NMD) is a translation-dependent mRNA decay mechanism that serves the purpose of controlling both mRNA quality and quantity. As a quality control mechanism, NMD protects organisms against the deleterious effects of mRNAs that encode premature termination codons, which arise through either transcriptional errors or genetic variation. NMD is also employed as a major regulator of physiological gene expression levels, and complete knockouts of multiple NMD genes are embryonic lethal in model organisms. The identification of genes that contribute to human Mendelian disease has now highlighted that gene variants that impact NMD function contribute to a spectrum of neurodevelopmental disorders (NDDs). Here, we capture the current landscape of NMD genes and gene variants implicated in NDDs with a focus on recent discoveries. The survey highlighted the involvement of more than half of all NMD and NMD-related genes in NDDs, representing a significant enrichment. That compromised NMD is a likely convergent pathogenic mechanism across multiple genetic causes of NDDs warrants ongoing investigation into the role of NMD in brain development.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"94 ","pages":"Article 102394"},"PeriodicalIF":3.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144780827","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}
Pub Date : 2025-08-06DOI: 10.1016/j.gde.2025.102387
Matteo Zambon , Federica Mantica , Mafalda Dias , Jonathan Frazer , Manuel Irimia
Comparative transcriptomic studies are key to understanding how molecular evolution drives phenotypic divergence across the tree of life. Here, we discuss three major directions in which the field of comparative transcriptomics is evolving. The first one is enabled by advances in sequencing technologies. Bulk RNA sequencing emerged two decades ago as a key tool to characterize transcriptomic states, enabling evolutionary comparisons at the tissue and organ levels. However, single-cell and spatial transcriptomics are now driving a shift toward a paradigm centered around cell types. Second, while comparative transcriptomic studies have historically focused on a few key model organisms and on species closely related to humans, recent trends have shifted toward both broader phylogenetic coverage and deeper sampling within clades. In parallel, the growing amount of transcriptomic data, together with the advent of machine learning approaches, are leading to the development of new modeling frameworks. These frameworks range from reconstruction of cell type phylogenies to prediction of RNA coverage from genomic sequence alone and have propelled significant progress in evolutionary biology and its biomedical applications.
{"title":"Evolution of comparative transcriptomics: biological scales, phylogenetic spans, and modeling frameworks","authors":"Matteo Zambon , Federica Mantica , Mafalda Dias , Jonathan Frazer , Manuel Irimia","doi":"10.1016/j.gde.2025.102387","DOIUrl":"10.1016/j.gde.2025.102387","url":null,"abstract":"<div><div>Comparative transcriptomic studies are key to understanding how molecular evolution drives phenotypic divergence across the tree of life. Here, we discuss three major directions in which the field of comparative transcriptomics is evolving. The first one is enabled by advances in sequencing technologies. Bulk RNA sequencing emerged two decades ago as a key tool to characterize transcriptomic states, enabling evolutionary comparisons at the tissue and organ levels. However, single-cell and spatial transcriptomics are now driving a shift toward a paradigm centered around cell types. Second, while comparative transcriptomic studies have historically focused on a few key model organisms and on species closely related to humans, recent trends have shifted toward both broader phylogenetic coverage and deeper sampling within clades. In parallel, the growing amount of transcriptomic data, together with the advent of machine learning approaches, are leading to the development of new modeling frameworks. These frameworks range from reconstruction of cell type phylogenies to prediction of RNA coverage from genomic sequence alone and have propelled significant progress in evolutionary biology and its biomedical applications.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"94 ","pages":"Article 102387"},"PeriodicalIF":3.6,"publicationDate":"2025-08-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144781425","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}
Pub Date : 2025-08-05DOI: 10.1016/j.gde.2025.102385
Bibhusita Pani , Evgeny Nudler
The primary objective of life is to ensure the faithful transmission of genetic material across generations, despite the constant threat posed by DNA-damaging factors. To counter these challenges, life has evolved intricate mechanisms to detect, signal, and repair DNA damage, thereby preventing mutations that can cause developmental abnormalities or diseases. DNA repair is especially vital during development — a period of rapid cell proliferation and differentiation. Failure to repair DNA damage in somatic cells can result in tissue dysfunction, while during embryonic development, it is often fatal. Transcription machinery plays a key role in the mechanisms of DNA repair. This review highlights current insights into DNA repair pathways that are driven or facilitated by transcription and their essential contribution to preserving genome stability.
{"title":"Transcription-coupled repair: protecting genome across generations","authors":"Bibhusita Pani , Evgeny Nudler","doi":"10.1016/j.gde.2025.102385","DOIUrl":"10.1016/j.gde.2025.102385","url":null,"abstract":"<div><div>The primary objective of life is to ensure the faithful transmission of genetic material across generations, despite the constant threat posed by DNA-damaging factors. To counter these challenges, life has evolved intricate mechanisms to detect, signal, and repair DNA damage, thereby preventing mutations that can cause developmental abnormalities or diseases. DNA repair is especially vital during development — a period of rapid cell proliferation and differentiation. Failure to repair DNA damage in somatic cells can result in tissue dysfunction, while during embryonic development, it is often fatal. Transcription machinery plays a key role in the mechanisms of DNA repair. This review highlights current insights into DNA repair pathways that are driven or facilitated by transcription and their essential contribution to preserving genome stability.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"94 ","pages":"Article 102385"},"PeriodicalIF":3.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144781424","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}
Pub Date : 2025-08-05DOI: 10.1016/j.gde.2025.102386
Peng Du , Jianlong Wang
{"title":"Editorial overview: 3Rs update: a new era in cellular identity and therapeutic plasticity","authors":"Peng Du , Jianlong Wang","doi":"10.1016/j.gde.2025.102386","DOIUrl":"10.1016/j.gde.2025.102386","url":null,"abstract":"","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"94 ","pages":"Article 102386"},"PeriodicalIF":3.6,"publicationDate":"2025-08-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144773219","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}
Pub Date : 2025-07-24DOI: 10.1016/j.gde.2025.102384
Leon Hilgers , Michael Hiller
Comparative genomics is a powerful approach to illuminate the genetic basis of phenotypic diversity across macro-evolutionary timescales. Recent advances in sequencing, genome assembly, annotation, and comparative methods promoted large-scale analyses that unveiled genomic determinants contributing to differences in cognition, metabolism, and body plans as well as phenotypes with biomedical relevance, such as cancer resistance, longevity, and viral tolerance. These studies highlight joint contributions of multiple molecular mechanisms and indicate an underappreciated role for gene and enhancer losses driving phenotypic change. However, challenges remain, including comprehensive phenotype databases and genome annotations, improved approaches for identifying lineage-specific adaptations, and functional tests. Here, we review recent progress, highlight major discoveries, and discuss future directions for linking phenotype to genotype using comparative genomics.
{"title":"Linking phenotype to genotype using comprehensive genomic comparisons","authors":"Leon Hilgers , Michael Hiller","doi":"10.1016/j.gde.2025.102384","DOIUrl":"10.1016/j.gde.2025.102384","url":null,"abstract":"<div><div>Comparative genomics is a powerful approach to illuminate the genetic basis of phenotypic diversity across macro-evolutionary timescales. Recent advances in sequencing, genome assembly, annotation, and comparative methods promoted large-scale analyses that unveiled genomic determinants contributing to differences in cognition, metabolism, and body plans as well as phenotypes with biomedical relevance, such as cancer resistance, longevity, and viral tolerance. These studies highlight joint contributions of multiple molecular mechanisms and indicate an underappreciated role for gene and enhancer losses driving phenotypic change. However, challenges remain, including comprehensive phenotype databases and genome annotations, improved approaches for identifying lineage-specific adaptations, and functional tests. Here, we review recent progress, highlight major discoveries, and discuss future directions for linking phenotype to genotype using comparative genomics.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"94 ","pages":"Article 102384"},"PeriodicalIF":3.7,"publicationDate":"2025-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144696870","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}
Pub Date : 2025-07-22DOI: 10.1016/j.gde.2025.102383
Masahiro Nagano , Mitinori Saitou
Germ cells are unique in their ability to acquire totipotency. Toward this end, they reorganize their three-dimensional (3D) epigenome during their development, including epigenetic reprogramming in primordial germ cells that differentiate mitotic prospermatogonia and ensuing unique epigenetic programming for generating undifferentiated spermatogonia/spermatogonial stem cells (SSCs). Advances in low-input epigenomic and 3D genomic techniques, along with complementary in-depth characterization of scalable in vitro reconstitution systems for germ cell development, that is, in vitro gametogenesis, have elucidated a number of fundamental events during these processes, including insulation augmentation in highly open chromatin following epigenetic reprogramming in mitotic prospermatogonia and insulation erasure and further euchromatization accompanied by chromosomal radial repositioning in undifferentiated spermatogonia/SSCs. These 3D epigenomic organizations likely serve as a foundation for generating fully functional gametes. Elucidating the mechanisms underlying 3D epigenomic reorganization during germ cell development will be instrumental not only for understanding the basis for totipotency but also for further advancing in vitro gametogenesis.
{"title":"Dynamic three-dimensional epigenomic reorganization for the development of undifferentiated spermatogonia in mice","authors":"Masahiro Nagano , Mitinori Saitou","doi":"10.1016/j.gde.2025.102383","DOIUrl":"10.1016/j.gde.2025.102383","url":null,"abstract":"<div><div>Germ cells are unique in their ability to acquire totipotency. Toward this end, they reorganize their three-dimensional (3D) epigenome during their development, including epigenetic reprogramming in primordial germ cells that differentiate mitotic prospermatogonia and ensuing unique epigenetic programming for generating undifferentiated spermatogonia/spermatogonial stem cells (SSCs). Advances in low-input epigenomic and 3D genomic techniques, along with complementary in-depth characterization of scalable <em>in vitro</em> reconstitution systems for germ cell development, that is, <em>in vitro</em> gametogenesis, have elucidated a number of fundamental events during these processes, including insulation augmentation in highly open chromatin following epigenetic reprogramming in mitotic prospermatogonia and insulation erasure and further euchromatization accompanied by chromosomal radial repositioning in undifferentiated spermatogonia/SSCs. These 3D epigenomic organizations likely serve as a foundation for generating fully functional gametes. Elucidating the mechanisms underlying 3D epigenomic reorganization during germ cell development will be instrumental not only for understanding the basis for totipotency but also for further advancing <em>in vitro</em> gametogenesis.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"94 ","pages":"Article 102383"},"PeriodicalIF":3.7,"publicationDate":"2025-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144680499","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}
Pub Date : 2025-07-18DOI: 10.1016/j.gde.2025.102382
Abigail Lind
The microbial community colonizing the animal gut includes all domains of life, including eukaryotic microbes. Historically viewed as pathogens, increasing evidence has revealed that many protists are commensal members of the microbiome with diverse ecological functions. This review synthesizes recent advances in our understanding of the ecology and evolution of these organisms, with a focus on phylogenetic diversity, microbial interactions, and genomic signatures of adaptation. New technologies such as single-cell genomics and transcriptomics, long-read sequencing technologies, and co-culture strategies have made these new findings possible, but much remains to be investigated. Further work is needed to understand how these diverse organisms contribute to the gut environment and evolve to colonize animal hosts.
{"title":"Evolution and ecology of commensal gut protists: recent advances","authors":"Abigail Lind","doi":"10.1016/j.gde.2025.102382","DOIUrl":"10.1016/j.gde.2025.102382","url":null,"abstract":"<div><div>The microbial community colonizing the animal gut includes all domains of life, including eukaryotic microbes. Historically viewed as pathogens, increasing evidence has revealed that many protists are commensal members of the microbiome with diverse ecological functions. This review synthesizes recent advances in our understanding of the ecology and evolution of these organisms, with a focus on phylogenetic diversity, microbial interactions, and genomic signatures of adaptation. New technologies such as single-cell genomics and transcriptomics, long-read sequencing technologies, and co-culture strategies have made these new findings possible, but much remains to be investigated. Further work is needed to understand how these diverse organisms contribute to the gut environment and evolve to colonize animal hosts.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"94 ","pages":"Article 102382"},"PeriodicalIF":3.7,"publicationDate":"2025-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144654706","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}
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