Molecular biology and evolution最新文献

{"title":"Phylogenomic subsampling and upsampling for efficient evolutionary analyses of big data.","authors":"Sudhir Kumar, Koichiro Tamura, Sudip Sharma","doi":"10.1093/molbev/msag218","DOIUrl":"10.1093/molbev/msag218","url":null,"abstract":"<p><p>Long runtimes, high memory demands, and reliance on high-performance computing impede phylogenomic analyses. We review a scalable phylogenomic subsampling with upsampling (PSU) framework to address this challenge, which reduces runtime and memory requirements by orders of magnitude. In PSU, small subsamples of sites from a concatenated alignment are analyzed, which are expanded by upsampling before inference, and the resulting inferences are aggregated to obtain evolutionary estimates. PSU harnesses the fact that the computational cost of maximum likelihood analysis is strongly influenced by the number of distinct site patterns in the concatenated alignment, whereas statistical power depends primarily on the amount of evolutionary information represented by the total number of sites and substitutions. By reducing the former while restoring the latter through upsampling, PSU can approximate many full-alignment analyses at substantially lower computational cost. Analysis of simulated and empirical datasets shows that PSU can accurately estimate bootstrap support values, select the optimal substitution model, test evolutionary hypotheses, and infer branch lengths, divergence times, and associated uncertainty measures. PSU also provides distributions of inferred clade support across independent subsamples, enabling detection of conflicting phylogenetic signals that may remain hidden in conventional bootstrap analysis of concatenated alignments. Automated tuning of subsample size, the number of subsamples, and the number of upsampling replicates make PSU practical. We suggest that PSU is a general approach for scalable phylogenomic inference using a broad range of statistical methods. By enabling analyses of genome-scale alignments on commodity hardware, PSU broadens research access and reduces environmental and infrastructural costs of big-data phylogenomics.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551623/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795518","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":"Adaptation to seasonal drought in Arabis alpina is linked to the demographic history and climatic changes since the last glacial maximum.","authors":"Bastiaan Tjeng, Mehak Mehak, Helene Bråten Grindeland, Jasmin Zohren, Andrea Dalla Libera, Jörg Wunder, Carlos Alonso-Blanco, George Coupland, Andrea Fulgione","doi":"10.1093/molbev/msag212","DOIUrl":"10.1093/molbev/msag212","url":null,"abstract":"<p><p>Understanding how species adapt to new environments is a central goal in evolutionary biology, and a topical question in climate change research. Here, we sequenced the genomes of 426 individuals of the perennial, Arctic-alpine herb Arabis alpina to study demography and adaptation, with a focus on populations in Northern Spain, that experience warm and dry summers. Our inference supports a scenario in which A. alpina colonized Northern Spain in a range expansion event that started near the Alps around 216 thousand years ago (kya). During the last glacial episode (115 to 12 kya), this expansion proceeded westward, and effective population sizes were large across Europe, likely due to a larger suitable habitat for A. alpina. These ancient demographic events gave rise to a highly diverged genetic lineage in Northern Spain. In the present interglacial (between 12 kya and present), populations became increasingly fragmented, and lost genetic diversity across Europe. Furthermore, we detected signatures of selection at genes associated with responses to abiotic stress, including drought stress, and regulation of growth, for instance at SC5D and NAC055, which reflects the climatic changes since the last glacial period. Notably, an ancient polymorphism at the gene FRL1 emerged as a candidate for conferring variation in flowering behavior, and for contributing to adaptation to drought. Our study suggests that the combination of ancestral variation in flowering behavior, and positive selection on new mutations involved in drought responses, underlies the evolution of a new trait syndrome, and adaptation to climate change.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13551622/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795406","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":"Conserved water molecules shape the pathogenicity of missense variants in human proteins.","authors":"Janez Konc, Karmen Recer, Tanja Kunej, Dušanka Janežič","doi":"10.1093/molbev/msag217","DOIUrl":"https://doi.org/10.1093/molbev/msag217","url":null,"abstract":"<p><p>Conserved water molecules (CWMs) are tightly bound solvent molecules that occupy well-defined, recurrent positions in protein structures. Although they are known to influence protein stability, function, and ligand binding, their role in shaping the effects of human missense variants remains largely unexplored. Here, we demonstrate that CWMs are a previously underappreciated determinant of missense variant pathogenicity. By predicting ligand-binding and CWM sites across human PDB structures and mapping missense variants to these sites and the remaining protein surface, we found that pathogenic variants were significantly enriched at CWM sites, whether overlapping or outside other ligand-binding regions. This enrichment exceeded that observed for binding sites as a whole, indicating a broader role for water-mediated interactions in modulating variant effects. To explore a mechanistic basis for this association, we performed molecular dynamics simulations of human lysosomal acid glucosylceramidase (GCase), encoded by GBA1 and implicated in Gaucher disease and Parkinson's disease risk. Selective destabilization of a CWM site in wild-type GCase produced structural and dynamical changes resembling those observed in the pathogenic L444P variant, whereas stabilization of this site in L444P shifted several measures toward wild-type behavior. These results suggest that disruption of a single CWM can contribute to long-range structural remodeling observed in a disease-associated variant. Together, our findings identify CWMs as a novel structural constraint shaping the distribution and effects of pathogenic missense variants. Incorporating water-mediated interactions into structural models provides a generalizable framework for interpreting human genetic variation and its contribution to disease.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148865219","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}

{"title":"Phylogenomics supports monophyly of marsupial crustaceans: a journey to direct development.","authors":"Anna-Chiara Barta, Markus Grams, Heather Bracken-Grissom, Saskia Brix, Lívia M Cordeiro, Brittany Cummings, Stormie Collins, William J Farris, Sarah Gerken, Christoph G Höpel, Anne-Nina Lörz, Siena McKim, Kenneth Meland, Luise Kruckenhauser, Jørgen Olesen, Pedro A Peres, Stefan Richter, Regina Wetzer, Jason Williams, Kevin M Kocot, Martin Schwentner","doi":"10.1093/molbev/msag178","DOIUrl":"https://doi.org/10.1093/molbev/msag178","url":null,"abstract":"<p><p>Peracarida (marsupial crustaceans) represent one of the most diverse and ecologically important crustacean groups, yet their evolutionary relationships have long been debated. Here, we present the most comprehensive phylogenomic analysis of Peracarida to date, incorporating the relict taxa Thermosbaenacea, Mictacea, Ingolfiellida, and Spelaeogriphacea in a phylogenomic framework. Our results robustly confirm peracarid monophyly and recover a well-supported clade uniting Mancoida (Isopoda, Tanaidaca, Cumacea, Spelaeogriphacea) and Mictacea. We propose for Mictacea to be classified as part of the Mancoida, which is defined by shared developmental and morphological traits. Thermosbaenacea is suggested as sister group to all other Peracarida, although this position was not recovered in all analyses. The inferred phylogeny further suggests that evolution of Peracarida involved a transition from an intermediate \"pseudodirect\" developmental mode to the direct development seen in most lineages. We further show that the shift to extensive brood care within the marsupium, accompanied by the loss of a free-swimming larval stage, may have accelerated rates of molecular evolution across lineages. Together, these findings provide a robust evolutionary framework for this major malacostracan lineage and highlight how key reproductive innovations reshaped the genomic and life-history trajectories of the marsupial crustaceans.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"43 8","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13472170/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148761522","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":"Convergent elevation of mitochondrial proton leakage improves thermogenesis in honeybees.","authors":"Ye Xiao, Lifei Qiu, Hao Wang, Yuanchan Fan, Zhunan Zhao, Dan-Yang Wu, Zhengwei Wang, Junzheng Zhang, Misbah A Malik, Sajad H Parey, Min Tang, Baojun Sun, Weiguo Du, Xin Zhou, Shanlin Liu","doi":"10.1093/molbev/msag174","DOIUrl":"10.1093/molbev/msag174","url":null,"abstract":"<p><p>The independent range expansions of the honeybees Apis cerana and A. mellifera from tropical origins into temperate environments have had profound ecological and agricultural impacts. Both species have convergently evolved enhanced thermogenic capacity relative to closely related taxa restricted to tropical and subtropical regions. However, the intrinsic physiological and molecular mechanisms enabling enhanced thermogenesis remain unclear. Here, we first show that A. cerana and A. mellifera exhibit increased proton leak, as evidenced by mitochondrial oxygen consumption assays, directly contributing to elevated heat production. Using a comparative framework supported by newly assembled high-quality genomes, we further identify accelerated evolution in mitochondrial metabolic pathways in both wide-ranged species. At the gene level, we identify Ptcd1 as a key candidate, showing signatures of positive selection and convergent amino acid substitution in both A. cerana and A. mellifera. Functional validation in Drosophila demonstrates that Ptcd1 promotes insect thermogenesis by modulating mitochondrial metabolism and ultrastructure. Moreover, knock-in Drosophila lines expressing Ptcd1 isoforms derived from A. cerana, the tropical species A. dorsata, and a targeted reversion mutation reveal that the Q208K substitution, unique to A. cerana and A. mellifera, increases proton leak and enhances heat generation. Together, these findings demonstrate that the independent fixation of a single amino acid change in PTCD1 has contributed to convergent enhancement of thermogenesis in both A. cerana and A. mellifera. This molecular innovation likely facilitated their expansion into temperate climates and highlights mitochondrial regulation as a fundamental axis of thermal adaptation shared across diverse animal lineages.</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/PMC13451093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471643","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":"Evolutionary adaptation proceeds through a small number of phenotypic modules.","authors":"Mohammad Hossein Donyavi, Reza Ghelich, Kara Schmidlin, Grant Kinsler, Kerry Geiler-Samerotte","doi":"10.1093/molbev/msag183","DOIUrl":"https://doi.org/10.1093/molbev/msag183","url":null,"abstract":"<p><p>Understanding how the myriad molecular impacts of mutation percolate to influence higher-order traits and ultimately fitness requires compressing a many-to-many mapping into something tractable. Decades of theoretical work suggest this may be possible because biological systems are modular: effects of perturbation are often funneled through particular pathways or subsystems rather than propagating freely through the organism. Yet, few empirical systems have been able to demonstrate such modularity at scale. Here, we show that, even across 774 diverse yeast lineages, fitness variation across 12 drug environments is organized by a strikingly low-dimensional structure defined by only a few inferred phenotypic axes that capture the main patterns of variation. Lineages drawn from multiple evolutionary histories reveal more of these phenotypic axes than those derived from a single selection pressure. Consistent with many of these lineages having evolved under strong selection pressure, their mutations often exhibit broad pleiotropy, affecting nearly all inferred phenotypic axes. However, fitness in any given drug depends on a much sparser subset of the phenotypic modules these axes reflect. By compressing many-to-many relationships, this low-dimensional framework exposes the modular phenotypic space, as well as the context-dependent contribution of each phenotypic module to fitness that can constrain the pleiotropic effects of adaptive mutations. It also highlights that the apparent complexity of genotype-phenotype-fitness maps depends not only on environmental context but also on the diversity of mutations through which they are observed, laying the groundwork for identifying the key phenotypic modules that matter for fitness.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"43 8","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13487634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795441","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":"Pig Matrix: a matched multiomics 3D regulatory genomics database for evolutionary and comparative analyses in pigs.","authors":"Chao Guo, Dezhi Hua, Shuang Gan, Yue-Dong Zhang, Hang Liu, Mengting Ding, Minghao Cao, Qiuhan Wen, Chen Yan, Jing-Sheng Lu, Lei Liu, Yi-Fan Jiang, Guoqiang Yi, Zhonglin Tang, Xiang-Dong Ding, Hai-Bing Xie, Zhong-Yin Zhou, Min-Sheng Peng, Ya-Nan Wang, Xuemei Lu, Ya-Ping Zhang","doi":"10.1093/molbev/msag190","DOIUrl":"10.1093/molbev/msag190","url":null,"abstract":"<p><p>The pig (Sus scrofa) is an important model for evolutionary, comparative, and translational research; however, current functional genomic resources in pigs remain largely limited to one-dimensional genomic annotation and are therefore insufficient for systematically resolving regulatory region-gene relationships, particularly distal ones. Here, we present the Pig Matrix database, a comprehensive 3D regulatory genomics database for pigs, available at https://pigmatrix.kiz.ac.cn/. Built on a standardized experimental framework, Pig Matrix integrates matched multiomics datasets across tissues, developmental stages, and porcine cell lines, including genomic, transcriptomic, epigenomic, and 3D genome information. In total, it contains 16 library types across 7 omics layers and 7,959 processed files from 1,170 libraries. By integrating epigenomic and 3D genome information, Pig Matrix links cis-regulatory elements (CREs) to putative proximal and distal target genes, thereby facilitating interpretation of noncoding variants and genomic signals. This database provides modules for genes, candidate CREs, 3D genome architecture, genome browsing, and single-cell transcriptomics, together with dedicated evolution and comparative resources and user-oriented Genome Annotation and LiftOver tools. A representative use case illustrates how 3D regulatory annotation extends interpretation beyond linear annotation alone, recovering additional candidate genes in domestication-related signals, notably including the classical domestication gene KIT. Pig Matrix also incorporates xenotransplantation-related resources and may support benchmarking of AI models for regulatory genomics. Together, Pig Matrix provides an integrated platform for regulatory interpretation, evolutionary analysis, and comparative genomics in pigs.</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/PMC13455638/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148630938","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":"Genetic background shapes the transcriptional activity and phenotypic contribution of a horizontally acquired region in yeast.","authors":"Andrés Romero, Camila Bastías, Matteo De Chiara, Xanita Saayman, Hajar Cherkaoui, Benjamin Barré, Francisco A Cubillos, Claudio Martínez, Eduardo I Kessi-Pérez, Gianni Liti, Francisco Salinas","doi":"10.1093/molbev/msag187","DOIUrl":"10.1093/molbev/msag187","url":null,"abstract":"<p><p>Horizontal gene transfer is the movement of genetic material across species. In Saccharomyces cerevisiae, a DNA segment known as Region B was acquired horizontally from a distant yeast species. This region (∼17 Kb) encodes five genes and is present in the genomes of yeast strains from different phylogenetic clades. Interestingly, the presence of Region B is not restricted to yeast strains isolated from fermentative environments, leaving its contribution to yeast niche-specific adaptation unclear. In this work, the genomic structure of Region B was analyzed in yeast strains from the ScRAP (S. cerevisiae Reference Assembly Panel) collection, identifying ten structural variants that maintain a circular continuity. To assess the role of Region B in yeast adaptation, we performed a high-throughput phenotyping of the ScRAP collection under different growth conditions, identifying that Region B is associated with higher tolerance to oxidative stress. Then, we characterized the transcriptional activity of each gene within Region B using a fluorescent reporter. The results revealed that gene expression depends on the host's genetic background and transcription factors encoded within Region B. To identify the genetic determinants involved in Region B expression within different genetic backgrounds, three expression quantitative trait loci were mapped and validated. Finally, by performing the deletion of Region B in two different strains, we determined a background-dependent contribution of this region to various fermentative phenotypes. Altogether, our results suggest a complex regulatory interaction between the horizontally acquired genes and the host genome that contributes to yeast adaptation under fermentation conditions.</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/PMC13447093/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562584","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":"Retraction of: Epistatic Effects Between Amino Acid Insertions and Substitutions Mediate Toxin resistance of Vertebrate Na+,K+-ATPases.","authors":"","doi":"10.1093/molbev/msag201","DOIUrl":"10.1093/molbev/msag201","url":null,"abstract":"","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"43 8","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13522922/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148840756","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":"ESL-PSC Toolkit: a graphical software environment for linking shared genetic changes to convergent phenotypes.","authors":"John B Allard, Sudhir Kumar","doi":"10.1093/molbev/msag205","DOIUrl":"10.1093/molbev/msag205","url":null,"abstract":"<p><p>Convergent evolution provides a useful framework for testing whether independent origins of similar traits share common genetic mechanisms. Evolutionary Sparse Learning with Paired Species Contrast (ESL-PSC) is an approach to identify genes and sites associated with convergent traits from aligned sequences by fitting sparse predictive models to phylogenetically informed species contrasts. However, practical use of ESL-PSC currently requires substantial command-line fluency and expertise for data assembly, species-pair design, and output interpretation. Here, we present an integrated ESL-PSC analysis environment (ESL-PSC Toolkit) centered on a graphical user interface (GUI). ESL-PSC Toolkit is designed to assist users from experimental design through data interpretation without requiring extensive technical expertise. It supports guided input validation, interactive tree-based pair selection, live execution, post-run exploration of ranked genes and aligned sites, a complementary substitution-counting method, and analysis of continuous quantitative convergent traits. The computational backend has been reimplemented in Rust with many performance optimizations and parallelism, greatly reducing runtime for most analyses and enabling cross-platform packaged distributions. Downloadable GUI and CLI toolkit software packages for Mac, Windows, and Linux are available at https://github.com/kumarlabgit/ESL-PSC/releases/latest.</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/PMC13511134/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148720781","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}