Pub Date : 2025-12-01Epub 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":"2025-12-01","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}
The gastrointestinal (GI) tract evolved in response to dietary changes and pathogen exposures that varied throughout history. As a major interface between the host and environment, the GI epithelia have evolved specialized barrier and immune functions while optimizing nutrient processing and absorption. Recent technological breakthroughs in modeling human biology in vitro and comparative single-cell genomics are providing novel insights into the genetic, cellular, and ontogenic basis of human evolution. In this review, we provide a broad overview of human-specific gut changes and how GI organoids and single-cell technologies can offer a mechanistic understanding of the specific features of human GI tract physiology.
{"title":"Human gut evolution: insights from stem cell models and single-cell genomics","authors":"Rubén López-Sandoval , Stefano Secchia , Joep Beumer , Jarrett Gray Camp","doi":"10.1016/j.gde.2025.102398","DOIUrl":"10.1016/j.gde.2025.102398","url":null,"abstract":"<div><div>The gastrointestinal (GI) tract evolved in response to dietary changes and pathogen exposures that varied throughout history. As a major interface between the host and environment, the GI epithelia have evolved specialized barrier and immune functions while optimizing nutrient processing and absorption. Recent technological breakthroughs in modeling human biology <em>in vitro</em> and comparative single-cell genomics are providing novel insights into the genetic, cellular, and ontogenic basis of human evolution. In this review, we provide a broad overview of human-specific gut changes and how GI organoids and single-cell technologies can offer a mechanistic understanding of the specific features of human GI tract physiology.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"95 ","pages":"Article 102398"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145151709","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 : 2025-12-01Epub Date: 2025-10-29DOI: 10.1016/j.gde.2025.102411
Alexander E Downie , Jenny Tung
Immune genes show remarkably consistent evidence of selection, modification, and diversification across the tree of life. Parasites are a key force in this process, but many questions remain about the genetic and phenotypic targets of parasite-mediated selection and how these connect to each other. Ecological immunology — the study of immune variation in natural settings — can complement genetic inference by providing an organismal perspective on immune evolution, including how immune adaptation may be explained or constrained by host life history and ecological context. In this review, we outline key questions in immune evolution where ecological immunology offers insights for evolutionary geneticists, and we explore the value of evolutionary genetic approaches for testing fundamental assumptions in ecological immunology.
{"title":"Evolutionary genetics meets ecological immunology: insights into the evolution of immune systems","authors":"Alexander E Downie , Jenny Tung","doi":"10.1016/j.gde.2025.102411","DOIUrl":"10.1016/j.gde.2025.102411","url":null,"abstract":"<div><div>Immune genes show remarkably consistent evidence of selection, modification, and diversification across the tree of life. Parasites are a key force in this process, but many questions remain about the genetic and phenotypic targets of parasite-mediated selection and how these connect to each other. Ecological immunology — the study of immune variation in natural settings — can complement genetic inference by providing an organismal perspective on immune evolution, including how immune adaptation may be explained or constrained by host life history and ecological context. In this review, we outline key questions in immune evolution where ecological immunology offers insights for evolutionary geneticists, and we explore the value of evolutionary genetic approaches for testing fundamental assumptions in ecological immunology.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"95 ","pages":"Article 102411"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145410717","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 : 2025-12-01Epub 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":"2025-12-01","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 : 2025-12-01Epub Date: 2025-11-11DOI: 10.1016/j.gde.2025.102412
Ricardo Muñiz-Trejo , Jaeda EJ Patton , Santiago Herrera-Álvarez , Joseph W Thornton
New methods are revealing the character of epistatic interactions within proteins and their impacts on evolution. Variation in biochemical phenotypes across protein sequences is determined primarily by the context-independent effects of amino acids and global nonlinearities imposed by biophysical mechanisms. Specific epistasis — primarily pairwise interactions — plays a subsidiary role, but collectively has a major impact on evolution. Every substitution in an evolving protein changes the effects of many potential mutations at epistatically coupled sites. As homologs diverge from common ancestors, the constraints that determine the accessibility of subsequent mutations gradually drift apart. Opportunities for adaptation and functional innovation also change over time, because each substitution epistatically modifies the effects of mutations on existing and new protein phenotypes. Over moderate evolutionary timescales, the outcomes of protein evolution — both their sequences and biochemical properties — thus become strongly contingent on the substitutions that happen to occur in each lineage. This interplay between random chance and each proteins’ epistatic architecture helps explain widely observed lineage-specific patterns of conservation and variation that are not expected under the dominant schools of thought in molecular evolution.
{"title":"Epistatic drift in protein evolution","authors":"Ricardo Muñiz-Trejo , Jaeda EJ Patton , Santiago Herrera-Álvarez , Joseph W Thornton","doi":"10.1016/j.gde.2025.102412","DOIUrl":"10.1016/j.gde.2025.102412","url":null,"abstract":"<div><div>New methods are revealing the character of epistatic interactions within proteins and their impacts on evolution. Variation in biochemical phenotypes across protein sequences is determined primarily by the context-independent effects of amino acids and global nonlinearities imposed by biophysical mechanisms. Specific epistasis — primarily pairwise interactions — plays a subsidiary role, but collectively has a major impact on evolution. Every substitution in an evolving protein changes the effects of many potential mutations at epistatically coupled sites. As homologs diverge from common ancestors, the constraints that determine the accessibility of subsequent mutations gradually drift apart. Opportunities for adaptation and functional innovation also change over time, because each substitution epistatically modifies the effects of mutations on existing and new protein phenotypes. Over moderate evolutionary timescales, the outcomes of protein evolution — both their sequences and biochemical properties — thus become strongly contingent on the substitutions that happen to occur in each lineage. This interplay between random chance and each proteins’ epistatic architecture helps explain widely observed lineage-specific patterns of conservation and variation that are not expected under the dominant schools of thought in molecular evolution.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"95 ","pages":"Article 102412"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145507846","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 : 2025-12-01Epub Date: 2025-11-15DOI: 10.1016/j.gde.2025.102414
Olga Rosspopoff , Didier Trono , Cédric Feschotte
Transposable elements (TEs) are abundant and dynamic components of eukaryotic genomes, subject to regulation by equally adaptive regulatory systems. A coevolution of TEs and zinc finger genes can be documented throughout metazoan evolution. In humans, TEs account for half of the genome, and nearly all TE subfamilies are preferentially bound by at least one of the approximately 400 KRAB zinc finger proteins (ZFPs). The majority of human KRAB-ZFPs appear to tame the cis-regulatory activities of TEs, thereby facilitating their integration within gene regulatory networks. In turn, throughout vertebrate evolution, TE protein domains have fused repeatedly with ZFPs to give rise to new classes of regulatory proteins. Thus, the TE–ZFP interplay has been a powerful catalyst of biological innovation.
{"title":"Mix-and-match between transposable elements and zinc finger proteins fuels genic and regulatory innovation","authors":"Olga Rosspopoff , Didier Trono , Cédric Feschotte","doi":"10.1016/j.gde.2025.102414","DOIUrl":"10.1016/j.gde.2025.102414","url":null,"abstract":"<div><div>Transposable elements (TEs) are abundant and dynamic components of eukaryotic genomes, subject to regulation by equally adaptive regulatory systems. A coevolution of TEs and zinc finger genes can be documented throughout metazoan evolution. In humans, TEs account for half of the genome, and nearly all TE subfamilies are preferentially bound by at least one of the approximately 400 KRAB zinc finger proteins (ZFPs). The majority of human KRAB-ZFPs appear to tame the <em>cis</em>-regulatory activities of TEs, thereby facilitating their integration within gene regulatory networks. In turn, throughout vertebrate evolution, TE protein domains have fused repeatedly with ZFPs to give rise to new classes of regulatory proteins. Thus, the TE–ZFP interplay has been a powerful catalyst of biological innovation.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"95 ","pages":"Article 102414"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145527962","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 : 2025-12-01Epub Date: 2025-11-06DOI: 10.1016/j.gde.2025.102413
Gayani Senevirathne , Terence D Capellini
Modern humans exhibit marked musculoskeletal changes when compared to those of our African ape relatives, such as chimpanzees, bonobos, and gorillas. These changes reflect adaptive shifts during hominin evolution in spine, pelvis, knee, and foot morphology toward obligate bipedalism, shoulder, elbow, and hand morphology for propulsive throwing and precision object manipulation, and brain size expansion and craniofacial morphology for enhanced cognition related to complex culture and language. The molecular basis for these traits remains unknown, in part owing to the experimental difficulties in connecting DNA base-pairs to phenotypes. Here, we discuss recent methodological advances in the life sciences that help to connect genotype to phenotype and pave the way for understanding the molecular basis for human skeletal evolution. In this context, we also discuss the importance of recent findings in how adaptive evolution shapes modern disease risk.
{"title":"New methodological approaches and insights gained toward understanding the evolved human skeleton","authors":"Gayani Senevirathne , Terence D Capellini","doi":"10.1016/j.gde.2025.102413","DOIUrl":"10.1016/j.gde.2025.102413","url":null,"abstract":"<div><div>Modern humans exhibit marked musculoskeletal changes when compared to those of our African ape relatives, such as chimpanzees, bonobos, and gorillas. These changes reflect adaptive shifts during hominin evolution in spine, pelvis, knee, and foot morphology toward obligate bipedalism, shoulder, elbow, and hand morphology for propulsive throwing and precision object manipulation, and brain size expansion and craniofacial morphology for enhanced cognition related to complex culture and language. The molecular basis for these traits remains unknown, in part owing to the experimental difficulties in connecting DNA base-pairs to phenotypes. Here, we discuss recent methodological advances in the life sciences that help to connect genotype to phenotype and pave the way for understanding the molecular basis for human skeletal evolution. In this context, we also discuss the importance of recent findings in how adaptive evolution shapes modern disease risk.</div></div>","PeriodicalId":50606,"journal":{"name":"Current Opinion in Genetics & Development","volume":"95 ","pages":"Article 102413"},"PeriodicalIF":3.6,"publicationDate":"2025-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145472530","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 : 2025-10-01Epub 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":"2025-10-01","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}
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