Molecular biology and evolution最新文献

{"title":"PHACE: Phylogeny-Aware Detection of Molecular Coevolution.","authors":"Nurdan Kuru, Ogün Adebali","doi":"10.1093/molbev/msaf150","DOIUrl":"10.1093/molbev/msaf150","url":null,"abstract":"<p><p>The coevolution trends of amino acids within or between genes offer key insights into protein structure and function. Existing tools for uncovering coevolutionary signals primarily rely on multiple sequence alignments, often overlooking phylogenetic relatedness and shared evolutionary history. Here, we introduce PHACE, a phylogeny-aware coevolution algorithm that maps amino acid substitutions onto a phylogenetic tree to detect molecular coevolution. PHACE categorizes amino acids at each position into \"tolerable\" and \"intolerable\" groups, based on their independent recurrence across the tree, reflecting a position's tolerance to specific substitutions. Gaps are treated as a third character type, with only phylogenetically independent gap changes considered. The method computes substitution scores per branch by traversing the tree and quantifying probability differences across adjacent nodes for each group. To avoid artifacts from alignment errors, we apply a multiple sequence alignment-masking procedure. Compared to phylogeny-based methods (CAPS, CoMap) and state-of-the-art multiple sequence alignment-based approaches (DCA, GaussDCA, PSICOV, mutual information), PHACE shows significantly superior accuracy in identifying coevolving residue pairs, as measured by statistical metrics including Matthews correlation coefficient, area under the ROC curve, and F1 score. This performance stems from PHACE's explicit modeling of phylogenetic dependencies, often ignored in coevolution analyses.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12264334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144608831","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":"Connectivity and Adaptation Patterns of the Deep-Sea Ground-Forming Sponge Geodia hentscheli Across Its Entire Distribution.","authors":"Sergi Taboada, Cristina Díez-Vives, Marta Turon, María Belén Arias, Carles Galià-Camps, Paco Cárdenas, Vasiliki Koutsouveli, Francisca Correia de Carvalho, Ellen Kenchington, Andrew J Davies, Shuangqiang Wang, Marta Martín-Huete, Emyr Martyn Roberts, Joana R Xavier, David Combosch, Ana Riesgo","doi":"10.1093/molbev/msaf145","DOIUrl":"10.1093/molbev/msaf145","url":null,"abstract":"<p><p>Geodia hentscheli, a species forming sponge grounds in the North Atlantic and Arctic Oceans, is a common deep-sea organism, that plays a fundamental role in forming biogenic habitats. However, there is little information about gene flow and adaptation patterns of this species, which is crucial to develop effective management/conservation plans under current global change scenarios. Here, we generated ddRADseq data from 110 specimens of G. hentscheli, together with microbial profiling, transcriptomics, and metatranscriptomics for a selection of specimens to investigate their genetic diversity, molecular connectivity, and local adaptations. Sampling covered the species' entire distribution within a wide bathymetric range. We obtained 1,115 neutral SNPs and identified long-distance genetic connectivity among regions separated 1,000s of km, but strong genetic structure segregating populations by depth at ca. 1,300 m, in line with our microbial analyses. Coalescent analyses inferred the split of these depth-related genetic entities ∼10 KYA, coincident with the last postglacial maximum. Analyses of SNPs under selection, combined with transcriptomic and metatranscriptomic data highlight the presence of several sponge genes and microbial metabolic pathways involved in adaptation to depth, including heat shock proteins and fatty acids, among others. The physiological plasticity of the sponge and its microbiome as a function of depth suggest the existence of a host-microbiome metabolic compensation for G. hentscheli. This study provides a multiscale paradigmatic example of the depth-differentiation hypothesis, a phenomenon mainly caused by changes in environmental conditions at different depths, mainly related to the presence of water masses with different characteristics that drive local adaptations.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12240736/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144234550","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":"Newly Developed Structure-Based Methods Do Not Outperform Standard Sequence-Based Methods for Large-Scale Phylogenomics.","authors":"Giacomo Mutti, Eduard Ocaña-Pallarès, Toni Gabaldón","doi":"10.1093/molbev/msaf149","DOIUrl":"10.1093/molbev/msaf149","url":null,"abstract":"<p><p>Recent developments in protein structure prediction have allowed the use of this previously limited source of information at genome-wide scales. It has been proposed that the use of structural information may offer advantages over sequences in phylogenetic reconstruction, due to their slower rate of evolution and direct correlation to function. Here, we examined how recently developed methods for structure-based homology search and tree reconstruction compare with current state-of-the-art sequence-based methods in reconstructing genome-wide collections of gene phylogenies (i.e. phylomes). While structure-based methods can be useful in specific scenarios, we found that their current performance does not justify using the newly developed structure-based methods as a default choice in large-scale phylogenetic studies. On the one hand, the best performing sequence-based tree reconstruction methods still outperform structure-based methods for this task. On the other hand, structure-based homology detection methods provide larger lists of candidate homologs, as previously reported. However, this comes at the expense of missing hits identified by sequence-based methods, as well as providing sets of homolog candidates with higher fractions of false positives. These insights help to guide the use of structural data in comparative genomics and highlight the need to continue improving structure-based approaches. Our pipeline is fully reproducible and has been implemented in a Snakemake workflow. This will facilitate a continuous assessment of future improvements of structure-based tools in the AlphaFold era.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528922","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":"Genome-wide Parallelism Underlies Rapid Freshwater Adaptation Fueled by Standing Genetic Variation in a Wild Fish.","authors":"Hao Yang, Yu-Long Li, Teng-Fei Xing, Jian-Hui Wu, Ting Wang, Ming-Sheng Zhu, Jin-Xian Liu","doi":"10.1093/molbev/msaf160","DOIUrl":"10.1093/molbev/msaf160","url":null,"abstract":"<p><p>A fundamental focus of ecological and evolutionary biology is determining how natural populations adapt to environmental changes. Rapid parallel phenotypic evolution can be leveraged to uncover the genetics of adaptation. Using population genomic approaches, we investigated the genetic architecture underlying rapid parallel freshwater adaptation of Neosalanx brevirostris by comparing four freshwater-resident populations with their common ancestral anadromous population. We demonstrated that the rapid parallel adaptation to freshwater followed a complex polygenic architecture and was characterized by genomic-level parallelism, which proceeded predominantly through repeated selection on the preexisting standing genetic variations. Frequencies of the genome-wide adaptive standing variations were moderate in the ancestral anadromous population, which had pre-adapted to fluctuating salinities. Relatively large allele frequency shifts were observed at some adaptive single-nucleotide polymorphisms (SNPs) during parallel adaptation to freshwater environments, with a large fraction of freshwater-favored alleles being fixed or nearly fixed. These adaptive SNPs were involved in multiple biological functions associated with osmoregulation, immunoregulation, locomotion, metabolism, etc., which were highly consistent with the polygenic architecture of adaptive divergence between the two ecotypes involving multiple complex physiological and behavioral traits. This work provides insight into the mechanisms by which natural populations rapidly evolve to changes in the environment and highlights the importance of standing genetic variation for the evolutionary potential of populations facing global environmental changes.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144560457","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":"A Trade-Off between Body Mass and Cancer Resistance in Cetaceans Is Mediated by Cell Cycle-Related Gene Evolution.","authors":"Linxia Sun, Yi Li, Huijie Zhang, Xinrui Chen, Guang Yang, Shixia Xu","doi":"10.1093/molbev/msaf159","DOIUrl":"10.1093/molbev/msaf159","url":null,"abstract":"<p><p>Cetaceans, well-known for their exceptionally long lifespans and substantial body masses, demonstrate a lower risk of cancer mortality compared to other mammals, consistent with Peto's paradox. Yet, the underlying mechanisms of cancer resistance, possibly evolved due to large body size, remain largely unclear. Here, we conducted an evolutionary analysis of 50 cell cycle-related genes, which play crucial role in both cancer progression and organismal body mass modulation, to investigate the mechanisms underlying the trade-off between body size and cancer resistance in cetaceans. We found that 66.7% (4/6) rapidly evolving genes (i.e. CDK2, CDT1, ORC3, and DBF4) and 50% (2/4) positively selected genes (ORC2 and ORC3) identified in cetaceans are involved in regulating cell cycle checkpoints, which halt the cell cycle in response to damage to allow repair and prevent cancer induction. Additionally, we identified four-body mass-associated genes (CCNE1, ORC5, E2F3, and DBF4) known to regulate cell growth; mutations or dysregulation of these genes can drive uncontrolled proliferation and cancer development. Interestingly, convergent evolution was observed in the African elephant and the bowhead whale at the tumor suppressor gene MYT1, potentially revealing a convergent mechanism of cancer resistance in large-bodied species. Notably, in vitro assays revealed that a cetacean-specific mutation M155T in the rapidly evolving gene CCND1 more effectively suppressed tumor cell proliferation and migration. Overall, our study has provided new insights into how the evolution of cell cycle-related genes balances body mass and cancer resistance in cetaceans, offering molecular support for Peto's paradox.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12279436/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144637646","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":"Extensive Recombination Suppression and Genetic Degeneration of a Young ZW Sex Chromosome System in Halfbeak Fish.","authors":"Teng-Fei Xing, Yu-Long Li, Hao Yang, Deborah Charlesworth, Jin-Xian Liu","doi":"10.1093/molbev/msaf151","DOIUrl":"10.1093/molbev/msaf151","url":null,"abstract":"<p><p>Sex chromosome systems have evolved independently across the tree of life, at different times in the past, and the evolutionary consequences of lacking recombination in sex-linked regions have been characterized in many old-established systems. However, empirical studies of young sex chromosomes are still scarce, especially in vertebrates. Integrating whole-genome sequencing data of two species of halfbeak fish, Hyporhamphus sajori and Hyporhamphus intermedius, we identified the sex-determining system in H. sajori as female heterogamety, involving a large fully sex-linked ZW region (∼26 Mb) on chromosome 5. The closest relative, H. intermedius, has a small sex-linked region on a different chromosome and shows male heterogamety, suggesting at least one turnover in this fish genus. The H. sajori sex-linked region includes two evolutionary strata, but the estimated Z-W divergence times are small, less than 3 million years for the older stratum, which is less than between the two species. Nevertheless, this evolutionarily young W-linked region is enriched with repetitive sequences, differs from the ancestral state by five inversions, and about one-third of its protein-coding genes have already become nonfunctional. Transcriptomic analysis suggests that some form of dosage compensation may already be evolving for some sex-linked genes.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12258149/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144485117","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":"Dynamics of Deleterious Mutations and Purifying Selection in Small Population Isolates.","authors":"Ying Chen, Xueyun Feng, Kerry Reid, Chaowei Zhang, Ari Löytynoja, Juha Merilä","doi":"10.1093/molbev/msaf110","DOIUrl":"10.1093/molbev/msaf110","url":null,"abstract":"<p><p>The genomic consequences of prolonged population decline and isolation are increasingly recognized, but quantitative assessments of mutation loads have been limited by low population-level replication in individual studies. Moreover, how inbreeding and purifying selection shape the genomic landscape of deleterious variation remains poorly understood. We evaluated the abundance and frequency of putative deleterious mutations, characterized the landscape of deleterious variation, and measured the efficacy of purifying selection in 17 wild nine-spined stickleback (Pungitius pungitius) populations covering varying levels of inbreeding (FROH = 0.015 to 0.912) and histories of isolation. We found significantly more deleterious homozygous mutations and a greater frequency of mildly deleterious variants in long-term small, isolated, and inbred populations than in larger outbred populations. Deleterious homozygotes were enriched in runs of homozygosity regions across all study populations, but the extent of enrichment was more pronounced in larger outbred populations than in small inbred populations. Historical effective population sizes serve as an indicator of the strength of purifying selection for mildly deleterious alleles but not for strongly deleterious alleles. The results demonstrate that the accumulation and purging of deleterious variants can occur simultaneously and that a large fraction of segregating strongly deleterious variants are recessive lethals. These findings, which are based on analyses of highly replicated samples of populations, suggest that the level of inbreeding is a good predictor of realized loads of deleterious mutations and that the genomic consequences of prolonged isolation in small populations are predictable.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"42 7","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12278730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144675291","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":"Detecting Interspecific Positive Selection Using Convolutional Neural Networks.","authors":"Charlotte West, Conor R Walker, Shayesteh Arasti, Viacheslav Vasilev, Xingze Xu, Nicola De Maio, Nick Goldman","doi":"10.1093/molbev/msaf154","DOIUrl":"10.1093/molbev/msaf154","url":null,"abstract":"<p><p>Traditional statistical methods using maximum likelihood and Bayesian inference can detect positive selection from an interspecific phylogeny and a codon sequence alignment based on model assumptions, but they are prone to false positives due to alignment errors and can lack power. These problems are particularly pronounced when faced with high levels of indels and divergence. To address these issues, we trained and tested convolutional neural network models on simulated data and achieved higher accuracy in detecting selection across a specific range of phylogenetic scenarios and evolutionary modes. This advantage is particularly evident when performing inference on noisy data prone to misalignments. Our method shows some ability to account for these errors, where most statistical frameworks fail to do so in a tractable manner. We explore the generalizability of our convolutional neural network models to unseen evolutionary scenarios and identify future avenues to achieve broader utility. Once trained, our convolutional neural network model is faster at test time, making it a scalable alternative to traditional statistical methods for large-scale, multigene analyses. In addition to binary classification (inference of the presence or absence of positive selection during the evolution of the sequences), we use saliency maps to understand what the model learns and observe how this could be leveraged for sitewise inference of positive selection.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":11.0,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12287699/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528921","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":"Horizontal Gene Transfer Inference: Gene Presence-Absence Outperforms Gene Trees.","authors":"Swastik Mishra, Martin J Lercher","doi":"10.1093/molbev/msaf166","DOIUrl":"10.1093/molbev/msaf166","url":null,"abstract":"<p><p>Horizontal gene transfer is a fundamental driver of prokaryotic evolution, facilitating the acquisition of novel traits and adaptation to new environments. Despite its importance, methods for inferring horizontal gene transfer are rarely systematically compared, leaving a gap in our understanding of their relative strengths and limitations. Validating horizontal gene transfer inference methods is challenging due to the absence of a genomic fossil record that could confirm historical transfer events. Without an empirical gold standard, new inference methods are typically validated using simulated data; however, these simulations may not accurately capture biological complexity and often embed the same assumptions used in the inference methods themselves. Here, we leverage the tendency of horizontal gene transfer events to involve multiple neighboring genes to assess the accuracy of diverse horizontal gene transfer inference methods. We show that methods analyzing gene family presence/absence patterns across species trees consistently outperform approaches based on gene tree-species tree reconciliation. Our findings challenge the prevailing assumption that explicit phylogenetic reconciliation methods are superior to simpler implicit methods. By providing a comprehensive benchmark, we offer practical recommendations for selecting appropriate methods and indicate avenues for future methodological advancements.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"42 7","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12301182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144732313","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":"Integrative Genomic, Transcriptomic and Epigenomic Analysis Reveals cis-regulatory Contributions to High-altitude Adaptation in Tibetan Pigs.","authors":"Dingwang Lai, Xiaolu Qu, Zhen Wang, Sang He, Xingzheng Li, Qi Bao, Guangming Sun, Jian Zhang, Yanbin Zhu, Guoqiang Yi","doi":"10.1093/molbev/msaf169","DOIUrl":"10.1093/molbev/msaf169","url":null,"abstract":"<p><p>The Qinghai-Tibet Plateau, characterized by its extreme environmental conditions, presents significant challenges to life, making it an ideal region for studying adaptation and evolution. Tibetan pigs, known for their high genetic diversity and exceptional adaptability to high altitudes, serve as excellent models for investigating high-altitude adaptation. While previous studies have extensively identified genetic determinants associated with high-altitude adaptation, the molecular mechanisms, particularly cis-regulatory patterns, remain poorly understood. Here, we conducted a selective sweep analysis using 484 genomes from Chinese and Western pig breeds across various altitudes, revealing 38.56 Mb of genomic regions under selection in Tibetan pigs. Enrichment analysis identified the lung as the primary functional tissue involved in high-altitude adaptation, supported by tissue-specific transcriptional and regulatory patterns observed between Tibetan and Meishan pigs (low altitude). By integrating genomic, RNA-seq, ATAC-seq, and H3K27ac HiChIP data, we constructed comprehensive enhancer-promoter regulatory maps of candidate genes and pinpointed promising genetic determinants associated with high-altitude adaptation, including SNPs in EPAS1, KLF13, SPRED1, and CFD. These loci were predicted to influence chromatin accessibility and the interactions of regulatory elements, with altered binding strength of relevant transcription factors. Further in vitro experiments confirmed that these loci function as allele-specific enhancers, modulating the expression of target genes. Our findings elucidate the regulatory basis of high-altitude adaptation in Tibetan pigs and provide valuable insights for exploring hypoxia-related diseases in livestock and humans.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2025-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12290512/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144612215","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}