Molecular biology and evolution最新文献

{"title":"The physicochemical basis of protein evolution: property-informed evolutionary models (PRIME).","authors":"Hannah Kim, Konrad Scheffler, Anton Nekrutenko, Darren P Martin, Steven Weaver, Ben Murrell, Sergei L Kosakovsky Pond","doi":"10.1093/molbev/msag200","DOIUrl":"10.1093/molbev/msag200","url":null,"abstract":"<p><p>Standard probabilistic models of coding sequence evolution effectively identify where and when selection acts but remain agnostic to the mechanistic realization of these forces. We introduce PRIME (PRoperty Informed Models of Evolution), a framework of codon-level maximum likelihood methods-including global (G-PRIME), episodic (E-PRIME), and site-specific (S-PRIME) implementations-that explicitly model amino acid exchangeability as a function of physicochemical properties. By parameterizing attributes such as molecular volume, hydropathy, and secondary structure propensities, PRIME aims to resolve the biophysical basis of selective constraint across both the sequence and the phylogeny. At the site level, S-PRIME leverages an explicit biophysical taxonomy to categorize residues as conserved, neutral, or changing for specific properties, resolving selective signals that are missed by traditional rate-based metrics. Our analysis of a benchmark of 24 diverse datasets and a genome-wide screen of 18,944 mammalian genes demonstrates that consideration of biophysical realism can yield substantial improvements in model fit, acting synergistically with rate variation to explain complex evolutionary patterns. We find that physicochemical constraints at individual sites can be reliably detected in datasets with sufficient information redundancy (substitutions per unique amino acid; AUC=0.91), with sensitivity exceeding 90% in data-rich alignments. E-PRIME reveals a distinct hierarchy in biophysical constraints: while core packing and beta-sheet scaffolds are rigidly conserved, alpha-helix propensity and surface electrostatics serve as the primary substrates for adaptive tuning. Furthermore, PRIME importance weights align with aspects of the primary semantic axes of deep learning representations (ESM-2) and capture key features of experimental fitness landscapes. By transforming abstract evolutionary rates into interpretable biophysical rules, PRIME provides a useful framework for characterizing the mechanistic drivers of protein diversity.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13511143/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148723518","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":"Correction to: The Fate of Horizontally Acquired Genes: Rapid Initial Turnover Followed by Long-Term Persistence.","authors":"","doi":"10.1093/molbev/msag176","DOIUrl":"10.1093/molbev/msag176","url":null,"abstract":"","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"43 7","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13397525/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148579524","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":"Phylogenomic blind spots: the limits of UCE and BUSCO loci in the presence of gene flow.","authors":"Nicole M Foley, William J Murphy","doi":"10.1093/molbev/msag155","DOIUrl":"10.1093/molbev/msag155","url":null,"abstract":"<p><p>Ultra-conserved elements (UCEs) and BUSCO genes are commonly used markers in reduced-representation phylogenomic studies. They are valued for their evolutionary conservation, ease of alignment, and cost-effectiveness in generating phylogenomic datasets for nonmodel species. Recombination-aware phylogenomic approaches reveal that, with increased historical and recent gene flow, the species tree may be limited to genomic regions with low recombination rates, whereas introgression-associated alleles are most often found in high-recombining regions. In this study, we aimed to determine whether widely used UCE and BUSCO datasets can reliably recover the species tree in mammalian clades where extensive introgression has previously been documented using recombination-aware methods. Our analyses indicate that UCEs and BUSCO loci are not sampled randomly from the genome and are underrepresented in mammalian sex chromosomes and other low-recombining genomic regions. Concatenation and coalescent-based phylogenomic analyses across 12 clades with varying degrees of gene flow showed that UCEs and BUSCO datasets do not recover the true species topology when introgression is frequent. Although neutral loci are generally preferred for phylogenomic analyses, per-base constraint measures estimated genome-wide show that UCE and BUSCO loci originate from genomic regions under very strong selective constraint. Comparisons of branch lengths and node heights from trees based on accelerated, neutral, and conserved PhyloP datasets revealed that those derived from UCE and BUSCO data are compressed relative to trees from neutral regions. We conclude by proposing mitigation strategies to address some of the issues identified in this study, thereby improving the use of UCE-based or other target-enrichment methods in phylogenomics.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13345375/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148345317","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":"Recent plastid replacement in Karlodinium ballantinum (Kareniaceae, Dinoflagellata) challenges the paradigms of endosymbiotic gene transfer.","authors":"Kacper Maciszewski, Kazuya Takahashi, Ryo Harada, Inga N Martinek, Takuro Nakayama, Mitsunori Iwataki, Yuji Inagaki, Elisabeth Hehenberger","doi":"10.1093/molbev/msag166","DOIUrl":"10.1093/molbev/msag166","url":null,"abstract":"<p><p>Plastids, the photosynthetic organelles of eukaryotes, arose via endosymbiosis of cyanobacteria by a eukaryotic host and were subsequently spread across eukaryotic diversity by additional endosymbioses. The process of plastid endosymbiosis is poorly understood, as most endosymbiotic events happened long ago. One group of microbial eukaryotes, the dinoflagellates, are characterized by their highly convoluted plastid evolution, particularly the family Kareniaceae, which have replaced their ancestral dinoflagellate plastid in most members with haptophyte plastids. To further explore the evolutionary history of kareniacean plastids, we obtained transcriptomic data from two representatives: Gertia stigmatica and Karlodinium ballantinum. We determined that Gt. stigmatica retained its ancestral plastid and that it is nested deep within the family Kareniaceae. Furthermore, the transcriptome shows no evidence of haptophyte plastid ancestry, indicating that a haptophyte plastid was likely never present. Conversely, K. ballantinum has abundant gene transfers originating from haptophytes, shared with other Kareniaceae. Surprisingly, K. ballantinum's plastid genome is nearly identical to that of extant haptophyte Gephyrocapsa huxleyi, but we were unable to identify gene transfers from this current plastid across the transcriptome. We therefore conclude that (i) the phylogenomic position of Gt. stigmatica and its retention of the ancestral plastid support at least two independent plastid replacements in Kareniaceae, and (ii) K. ballantinum has replaced its plastid organelle twice, with the second replacement being as yet unaccompanied by endosymbiotic gene transfer. Phylogenomics of plastid genomes suggests that the unusually high plastid replacement rate in Kareniaceae might be caused by accelerated mutation of the plastid genome within the host. Highlights Gertia stigmatica is the first known dinoflagellate in the family Kareniaceae without a haptophyte-derived plastid. Karlodinium ballantinum recently acquired its new plastid from a close relative of the haptophyte Gephyrocapsa huxleyi. Integration of a new plastid does not require large-scale endosymbiotic gene transfer. Plastids in Kareniaceae may require frequent replacement due to their accelerated evolution.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13394690/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148397263","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":"Severe bottleneck of ancient Homo populations: insights from computational modeling and relevant fossil evidence.","authors":"Sumei Zhou, Yiwen Zhou, Fabio Di Vincenzo, Giorgio Manzi, Wangjie Hu, Ziqian Hao, Zhen Shao, Yi-Hsuan Pan, Haipeng Li","doi":"10.1093/molbev/msag157","DOIUrl":"10.1093/molbev/msag157","url":null,"abstract":"<p><p>Reconstructing ancient population size history is essential for understanding the evolutionary origin of Homo sapiens. We recently developed the fast infinitesimal time coalescent process (FitCoal) and detected a severe population bottleneck occurring approximately 930 thousand years ago. However, two recent studies compared FitCoal and mushi and concluded that the severe bottleneck is a statistical artifact. In this study, we compared the two methods against a benchmark of 10 billion msprime coalescent simulations. We demonstrate that FitCoal achieves both superior speed and accuracy in expected site frequency spectrum (SFS) estimation. Analyses of simulated datasets confirmed that FitCoal reliably recovers the bottleneck, whereas mushi fails under identical conditions. Independent fossil and paleoclimate evidence is consistent with the timing and evolutionary impact of this bottleneck, including associations with hominin dispersals, speciation events, and a subsequent increase in brain size. These findings refine the demographic history of Homo during the Pleistocene and highlight the importance of high-precision SFS computation for revealing critical evolutionary transitions that shaped modern human ancestry.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13367442/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148376069","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":"Bayesian credible sets for phylogenetic tree topologies with applications to coverage analysis and cross-model comparison.","authors":"Jonathan Klawitter, Alexei J Drummond","doi":"10.1093/molbev/msag141","DOIUrl":"10.1093/molbev/msag141","url":null,"abstract":"<p><p>Credible intervals and credible sets, such as highest posterior density intervals, form an integral statistical tool in Bayesian phylogenetics, both for phylogenetic analyses and for development. Readily available for continuous parameters such as base frequencies and clock rates, the vast and complex space of tree topologies poses significant challenges for defining analogous credible sets. Traditional frequency-based approaches are inadequate for diffuse posteriors where sampled trees are often unique. To address this, we introduce novel and efficient methods for estimating the credible level of individual tree topologies using tractable tree distributions, specifically conditional clade distribution (CCD). Furthermore, we propose a new concept called α credible CCD, which encapsulates a CCD whose trees collectively make up α probability. We present algorithms to compute these credible CCDs efficiently and to determine credible levels of tree topologies as well as of subtrees. We evaluate the accuracy of these credible set methods leveraging simulated and real datasets. Furthermore, to demonstrate the utility of our methods, we use well-calibrated simulation studies to evaluate the performance of different CCD models. In particular, we show how the credible set methods can be used to conduct rank-uniformity validation and produce empirical cumulative distribution function plots, supplementing standard coverage analyzes for continuous parameters.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13325671/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148226678","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Fate of Horizontally Acquired Genes: Rapid Initial Turnover Followed by Long-Term Persistence.","authors":"Swastik Mishra, Käthe Weit, Martin J Lercher","doi":"10.1093/molbev/msag146","DOIUrl":"10.1093/molbev/msag146","url":null,"abstract":"<p><p>A major driver of bacterial evolution is horizontal gene transfer (HGT), the acquisition of genes from other strains or species. Transfers between closely related taxa are more likely to succeed, while the pervasive deletion bias of bacterial genomes drives frequent turnover of horizontally acquired genes. However, whether the rate of gene loss after acquisition is constant across lineages or time remains unclear. Here, we analyze a comprehensive dataset of bacterial genomes to infer the frequency, distribution, and retention of inter-phylum HGT events. The retention of inter-phylum gene transfers is highly skewed, with only a small subset of bacterial genomes accounting for the majority of such events. Most transferred genes are lost rapidly. Those genes that survive the initial purging are retained over long periods, are biased toward functions such as transport and metabolism, and have larger numbers of protein-protein interactions.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"43 7","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13364776/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148437475","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":"Why structural divergence varies among residues in enzyme evolution: contributions of mutation, stability, and activity constraints.","authors":"Julian Echave, Mathilde Carpentier","doi":"10.1093/molbev/msag162","DOIUrl":"10.1093/molbev/msag162","url":null,"abstract":"<p><p>In enzyme evolution, structural divergence varies among residues, forming residue-dependent structural divergence profiles. The evolutionary constraints that determine these profiles remain unclear. We build on the mutation-stability-activity (MSA) model, a mechanistic mutation-selection model previously developed for sequence evolution. In the MSA model, mutations become fixed or are lost depending on their effects on stability and activity, with parameters aS and aA controlling selection on stability and activity, respectively. The Linearly Forced Elastic Network Model (LFENM) is used to calculate mutational effects on structure, stability, and activity. As substitutions accumulate, structural changes build up unevenly across residues, producing a structural divergence profile that depends on how each residue responds to mutation and on how strongly selection acts on stability and activity. Applied to 34 enzyme families, the MSA model recapitulates observed structural divergence profiles, and nested model comparisons show that mutation, stability, and activity constraints each contribute. However, the balance among these constraints varies widely across families: mutation always contributes substantially, but stability and activity contributions range from negligible to dominant, so any of the three can prevail in a given family. These variations have distinct origins: the mutation contribution depends on how unevenly the protein's flexibility is distributed across residues, while the stability and activity contributions depend on how strongly selection acts, as quantified by aS and aA. The MSA model thus recovers family-specific selection strengths from structural divergence profiles, suggesting these profiles encode information not only about enzyme architecture but also about the selective regime under which enzymes evolve.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"43 7","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13401336/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592688","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":"Functional divergence and structural changes of Class IV histone deacetylases (HDACs) across the tree of life.","authors":"Zora Nováková, Pavla Bartošová-Sojková, Júlia Kudláčová, Fady Baselious, Zsófia Kutilová, Pavlína Jaklová, Marat Meleshin, Lucia Motlová, Andrea Schenkmayerova, Vladimír Vrkoslav, Štěpán Strnad, Natan Horáček, Ansgar Gruber, Petr Žáček, Sebastian Kroll, Barbora Havlínová, Markéta Ondráková, Růžena Tučková, Tereza Krunclová, Josef Cvačka, Miroslav Oborník, Mike Schutkowski, Wolfgang Sippl, Cyril Bařinka","doi":"10.1093/molbev/msag150","DOIUrl":"10.1093/molbev/msag150","url":null,"abstract":"<p><p>Class IV histone deacetylases (HDACs) are the least understood branch of the classical zinc-dependent HDAC family with HDAC11 standing out as the sole member of Class IV HDACs. Using a broad phylogenetic dataset spanning bacteria, archaea, and eukaryotes, we identified two deeply conserved HDAC11 lineages, clades A and B, that differ in evolutionary origin, predicted subcellular localization, and enzymatic properties. Clade A is enriched in phototrophic eukaryotes and targeted to mitochondria or plastids, whereas clade B predominates in heterotrophs and localizes mainly to the cytoplasm or nucleus. High-resolution crystal structures of selected representatives from each clade revealed a conserved catalytic core but distinct structural features-including electrostatic surface profiles, loop architectures, and foot pocket geometries-that clearly separate the two lineages and act as sequential \"selectivity filters\" shaping substrate specificity. Biochemical assays show robust long-chain fatty acid deacylase activity in clade B enzymes, but no detectable activity for any of clade A representatives against peptide substrates, suggesting adaptation to alternative, nonpeptidic targets. Together, these findings define a revised evolutionary framework for HDAC11 and provide structural and functional insights into the diversification of this ancient enzyme family.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13325672/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148271434","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":"Population epigenetics: deciphering DNA methylation diversity and its implications for health, disease, and evolution.","authors":"Shuangshuang Cheng, Shuhua Xu","doi":"10.1093/molbev/msag160","DOIUrl":"10.1093/molbev/msag160","url":null,"abstract":"<p><p>Population epigenetics investigates the distribution, determinants, and evolutionary significance of epigenetic variation, particularly DNA methylation (DNAm), within and among human populations. In this review, we synthesize recent advances in population epigenetics with an explicit evolutionary perspective, focusing on 3 interconnected dimensions. First, we outline patterns of DNAm variation, including tissue-, cell-, and developmental-stage specificity. Second, we examine the sources of DNAm variation, highlighting population-specific methylation quantitative trait loci, ancestry-related genetic architecture, and environmental modulators such as diet, climate, pollution, and lifestyle. Third, we explore evolutionary and clinical implications, linking DNAm variation to phenotypic plasticity, disease susceptibility, and adaptive processes shaped by natural selection. Comparative population studies demonstrate that genetic ancestry accounts for a substantial proportion of DNAm differentiation, reflecting the joint effects of allele-frequency divergence, linkage disequilibrium structure, and demographic history. At the same time, environmentally induced methylation changes introduce a dynamic and rapidly responsive layer of molecular diversity that can mediate short-term adaptation to local environments. Despite rapid progress, key challenges remain, including disentangling genetic, environmental, and technical confounders, assessing the stability and heritability of population-specific DNAm patterns, and establishing causal links between methylation, fitness-related traits, and selection. Looking ahead, advances in large-scale multi-ancestry cohorts, single-cell and long-read epigenomics, and integrative multi-omics will enable high-resolution mapping of epigenetic variation across populations. By bridging evolutionary theory, epigenetic epidemiology, and functional genomics, population epigenetics offers a powerful framework for understanding human adaptation, health disparities, and precision medicine in an evolutionary context.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13381286/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148368985","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}