Molecular biology and evolution最新文献

{"title":"Environmental and mutational modulation of collateral fitness effects informs their mechanisms.","authors":"Cameron Goff, Erh-Yeh Tsou, Jacob D Mehlhoff, Marc Ostermeier","doi":"10.1093/molbev/msag106","DOIUrl":"https://doi.org/10.1093/molbev/msag106","url":null,"abstract":"<p><p>Fitness effects of mutations that do not arise from changes in a protein's ability to perform its physiological functions (called collateral fitness effects or CFEs) are an understudied aspect of fitness landscapes. We have previously systematically measured the CFEs of all possible single amino acid substitutions in four proteins and found the frequency of deleterious mutations to vary by two orders of magnitude. Of these proteins, TEM-1 β-lactamase had the highest frequency, and deleterious mutations caused TEM-1 aggregation. Here, we systematically measured TEM-1 collateral fitness landscapes in environments and situations expected to alter protein aggregation or protein stability. We found a moderate correlation between deleterious CFEs and predicted thermodynamic stability effects in TEM-1's α-domain. Empirically, we found that the frequency and magnitude of deleterious CFEs can be reduced by altering the growth environment to disfavor aggregation (i.e. reducing the growth temperature or shifting to minimal media) or by stabilizing TEM-1 (via the M182T mutation or the addition of the β-lactamase inhibitor avibactam to the growth medium). However, although raising the growth temperature to favor aggregation exacerbated deleterious CFEs of many mutations, many mutations' effects were reduced. Furthermore, although reductions in CFEs occurred with reductions in TEM-1 aggregation for some mutants, for many mutants they did not. We propose that mutational destabilization exposes protein motifs that can cause deleterious CFEs, but that these motifs and those that cause aggregation are not necessarily the same motifs.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147729430","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":"Adaptive evolution of odorant receptors is associated with elaborations of social organization in ants.","authors":"Yoann Pellen, Joel Vizueta, Erin Beck, Juergen Liebig, Lukas Schrader, Eyal Privman","doi":"10.1093/molbev/msag103","DOIUrl":"https://doi.org/10.1093/molbev/msag103","url":null,"abstract":"<p><p>Cooperation in social insect colonies depends on complex chemical communication, requiring a large array of chemosensory receptors. Ant odorant receptors (ORs) were dramatically expanded compared to other insects, most notably in the \"9-exon\" subfamily, which was implicated in responding to cuticular hydrocarbons, a major class of signalling compounds. These observations indicate adaptive evolution of olfactory functions, but this process was never studied in the context of the evolution of specific sociobiological traits. The Global Ant Genomics Alliance has compiled 163 high-quality ant genomes, enabling detailed study of OR evolution in unprecedented detail. Analysing 55,068 ORs across the phylogeny, we tested for association between sociobiological traits and adaptive evolution of ORs, including gene duplication and adaptive sequence evolution. We identified strong enrichment of positive selection on 9-exon ORs in the ancestor of the formicoid clade, which evolved larger colonies and greater reproductive division of labour. This result indicates a key role of chemical communication in the early evolution of complex social organization. We also observed enrichment of positive selection on 9-exon ORs associated with the recent evolution of continuous worker polymorphism in multiple lineages. Surprisingly, the evolution of other sociobiological traits was associated with reduced positive selection on ORs. These results suggest that worker polymorphism involves more extensive adaptation of chemical communication compared to other aspects of ant sociobiology. By analysing the most comprehensive OR dataset to date, we provide new insights into the specific context in which ORs played a major role in the elaboration of social traits in ants.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698659","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":"Genome-wide SNP data reveals hidden hierarchic population structure and demographic history of endangered black-and-white snub-nosed monkeys (Rhinopithecus bieti).","authors":"Yitian Li, Zhiru Xu, Yingli Jiang, Minglin Chen, Yuan Li, Fan Liu, Jia Luo, Jiachao Feng, Weimin Kuang, Li Yu","doi":"10.1093/molbev/msag104","DOIUrl":"https://doi.org/10.1093/molbev/msag104","url":null,"abstract":"<p><p>The endangered black-and-white snub-nosed monkey (Rhinopithecus bieti), endemic to high-altitude forests in southwest China, has increased from fewer than 1,500 individuals pre-1990 to over 3,500 post-2010. However, it faces severe habitat fragmentation, with at least 20 isolated groups. Comprehensive investigation of large-scale population genomic analysis is lacking. We present the first comprehensive genomic reassessment of this species using fecal-DNA and targeted capture sequencing to generate genome-wide single nucleotide polymorphism data for 309 individuals. We identified five distinct genetic populations (Southwest, Southeast, Central, North-Central, North) with strong geographic associations. Furthermore, we found previously unrecognized subpopulations, primarily associated with isolation within human-altered landscapes. Roads and human settlements were the primary barriers to genetic connectivity. Genetic diversity is highest centrally and declines peripherally, reflecting historical/recent barriers. Demographic inference suggests: i) a possible southwestern origin and northward dispersal at ∼128.5-8.2 ka, probably driven by late Pleistocene climatic oscillations and local refugia; ii) major subpopulation divergences within the last ∼610-120 years ago, likely due to human exploitation; and iii) a sharp decline ∼300 years ago, leaving extremely low effective population size (40-314). Admixture origins of both Southeast and North-Central populations highlight its role in facilitating gene flow. Historically habitats with high connectivity contrast with current severe fragmentation, particularly in the southern regions; this persistent suitability disparity suggests limited historical connectivity promoting genetic divergence between southern and central/northern populations. Our results provide critical insights into the population structure and evolutionary history of R. bieti, offering critical insights for conservation and demonstrating the power of fecal genomics in endangered species.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147698661","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":"Multiple losses of ecdysone receptor genes in nematodes: an alternative evolutionary scenario of molting regulation.","authors":"Shumpei Yamakawa, Lisa-Marie Barf, Andreas Hejnol","doi":"10.1093/molbev/msag102","DOIUrl":"https://doi.org/10.1093/molbev/msag102","url":null,"abstract":"<p><p>Molting is a hallmark feature of ecdysozoans, including arthropods, tardigrades, and nematodes. Ecdysone hormones play a crucial role in regulating the molting process of different ecdysozoan taxa. Interestingly, despite this highly conserved function of ecdysone, the model nematode Caenorhabditis elegans has lost the ecdysone receptor (ECR) genes and their molting appears to be ecdysone-independent. The loss of ecr has only been reported in Caenorhabditis within ecdysozoans, and the evolutionary background behind this loss has remained enigmatic. Here, we show that loss of ecr is not exceptional in Caenorhabditis, but has occurred at least three times in Rhabditina and Tylenchina nematodes. Our genome-wide analysis of 160 nematode species revealed multiple losses of ecr and its typical heterodimer partner usp during nematode evolution. Furthermore, using transcriptomic, pharmacological, and in silico/in vivo protein interaction analyses, we identified two factors that potentially underlie and buffer the loss of ECR gene/function: (1) molting regulation by an alternative nuclear receptor HR3 (NHR-23) and (2) a lineage-specific expansion of nuclear receptors in the ecr-deficient taxa. Taken together, this study shows how key regulators of ecdysozoan molting can be altered during evolution. We propose a novel scenario for the evolution of molting regulation in nematodes.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147691176","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":"Phylogenomic mixture models outperform homogeneous and partitioned models.","authors":"Davide Pisani, Mattia Giacomelli, Gergely J Szöllősi, Maria Eleonora Rossi, Marc Domènech, Jesus Lozano-Fernandez","doi":"10.1093/molbev/msag090","DOIUrl":"https://doi.org/10.1093/molbev/msag090","url":null,"abstract":"<p><p>Significant advances have been made in resolving the tree of life, but many nodes remain debated. The last two decades saw the emergence of mixture models, which proved particularly useful to account for across-site compositional heterogeneity, and played a central role to improve our understanding of difficult phylogenetic problems. However, some scholars have remained skeptical of their use. Here we perform a large simulation study comparing mixture models accounting for across-site compositional heterogeneity, across-site compositionally homogeneous models and partitioned models. We show that the tested mixture models fit across-site compositionally heterogeneous datasets best and achieve greater accuracy. CAT-GTR, an infinite mixture model combining a General Time Reversible -GTR- matrix with a mixture of site-frequency profiles (i.e. categories -CAT- or components) characterized by different amino acid frequency vectors, maximizes accuracy and fit. Mixture models, and particularly CAT-GTR, perform well also with across-site compositionally homogeneous datasets, where the use of a mixture of site-frequency profiles is not necessary. We show that this is because with homogeneous data these models converge to appropriate compositionally homogeneous models, avoiding overparametrization. Our results dissipate doubts about the utility of models accounting for compositional heterogeneity across sites and identify CAT-GTR as one of the most flexible models in the phylogenomic arsenal.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147675229","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":"Transgenerational effects of heat shock on gene regulation and fitness-related traits in natural Drosophila populations.","authors":"Ewan Harney, Josefa González","doi":"10.1093/molbev/msag069","DOIUrl":"10.1093/molbev/msag069","url":null,"abstract":"<p><p>Heat stress will increasingly affect populations as climate change leads to higher temperatures and more frequent heat waves. Recent work suggests that interactions between the epigenome and transposable elements (TEs) could link environmental acclimation with rapid evolution. Yet little is known about how these processes interact in natural genetic backgrounds or shape evolutionarily relevant phenotypes. To investigate these interactions, we carried out laboratory experiments measuring gene expression and chromatin accessibility responses to heat shock in female D. melanogaster from arid and cold climates, their associations with population variation in TEs, and fitness-related phenotypes including viability and development time in the offspring. We also measured expression, accessibility and phenotypic traits three generations later to explore transgenerational inheritance. Expression and accessibility responses to heat shock varied between populations and were influenced by TE presence, with more upregulated responses in the arid population. Effects of heat shock on transcription were detected three generations later, especially in the arid population, although this was not driven by chromatin accessibility. Among offspring of heat shocked flies, phenotypes of the initial cohort (eggs laid within 2 d of heat shock) were negatively affected in both populations, but later cohorts (eggs laid more than 2 d after heat shock) from the arid population developed quicker than controls, indicating hormesis. This effect was still present four generations after the heat shock in the great-great-grandoffspring, demonstrating transgenerational inheritance of potentially beneficial phenotypes and gene expression in a natural insect population.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":"43 4","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13064987/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633882","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 key regulator of missing-self innate immunity is polymorphic and under diversifying selection.","authors":"Rocco F Notarnicola, Magdalena Herdegen-Radwan, Joanna Różańska-Wróbel, Mateusz Konczal, Karolina Przesmycka, Petr Kotlík, Wiesław Babik, Jacek Radwan","doi":"10.1093/molbev/msag082","DOIUrl":"10.1093/molbev/msag082","url":null,"abstract":"<p><p>Host-parasite co-evolution drives the diversification of host immune genes involved in the recognition of pathogen antigens and molecular patterns. In contrast, the immune genes involved in self-recognition and inhibition of immune responses against self-cells (missing-self immunity) may be evolutionarily constrained by the need to interact with self-components. However, many pathogens, such as the Lyme disease agent Borrelia, hijack these genes to evade the immune system and may therefore select for their diversification. How these contrasting but concurrent selective forces shape the evolution of missing-self regulators is not clearly understood. To fill this gap, we investigated polymorphism and molecular signatures of selection acting on a missing-self regulator, the complement factor H (CFH), in bank vole populations, which are an important wild reservoir for Borrelia. We then compared the geographic structuring in the CFH domain interacting with Borrelia (CCP 20) against a genomic background represented by RAD-seq markers. We found signals of positive and diversifying selection at CCP 20, suggesting that CFH evolved in response to pressures from pathogens. Additionally, we found other innate immunity genes within the alternative complement pathway, which is regulated by CFH, under diversifying selection, highlighting its involvement in host-parasite coevolution. This study demonstrates that an innate missing-self sensor in a wild vertebrate is under diversifying selection, likely driven by pathogens.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13102179/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147633862","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":"DiagnoDating: diagnostics for dated phylogenies in microbial population genetics.","authors":"Xavier Didelot, Jake Carson, Paolo Ribeca, Erik Volz","doi":"10.1093/molbev/msag093","DOIUrl":"10.1093/molbev/msag093","url":null,"abstract":"<p><p>Microbial population genetic studies often involve the use of a dated phylogeny to show how the genomes are related over a relevant timescale. Many tools have recently been developed to date the nodes of a standard phylogeny, but all make underlying assumptions that may not be realistic for a given dataset, making the results potentially unreliable. Model comparison is sometimes used to remedy this issue, whereby inference under several models is compared to establish which result can be trusted. Although such comparison is clearly useful to assess the relative merits of several inference attempts, here instead we focus on the problem of evaluating how good an inference is in absolute terms, without comparison. We consider several approaches for diagnosing potential issues in a reconstructed dated phylogeny, including outlier detection, posterior predictive checking and residual analysis. These methods are well-established diagnostics tools in other areas of statistics, but here we show how they can be applied to the specific inference of dated phylogenies. We illustrate their use on many simulated datasets, with inference being performed either from the correct model to quantify the specificity or from an incorrect model to quantify the sensitivity of the diagnostics methods. We also applied the methods to three real-life datasets to showcase the range of issues that they can detect. We have implemented the methods in a new R package entitled DiagnoDating. We advocate the use of these diagnostics tools for all microbial population genetic studies that involve the reconstruction of a dated phylogeny.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13103887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147675188","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":"Integrated conjugative elements drive the formation of pandemic clones of Escherichia coli with hybrid chromosomes.","authors":"Talía Berruga-Fernández, Douglas L Huseby, Oksana Koshla, Anum Shaukat, Arijana Katana, Rama Sayed, Giorgia Marino, Diarmaid Hughes","doi":"10.1093/molbev/msag085","DOIUrl":"10.1093/molbev/msag085","url":null,"abstract":"<p><p>Pathogenic multidrug-resistant bacteria with hybrid chromosomes have emerged as a significant global healthcare threat. These include the pandemic Escherichia coli ST1193, the product of homologous recombination events involving two phylogenetically distant strains of E. coli, in which mutant alleles of the widely separated genes, gyrA and parC, generating high-level fluoroquinolone resistance were acquired. The mechanisms and frequency of hybrid formation are poorly understood. We developed a robust hybrid selection procedure and applied it to 118 clinical UTI isolates of E. coli mixed with suitable recipient strains. Hybrids were selected from 39% of isolates. All hybrids were recombinants of donor and recipient chromosomal DNA (median length of donor DNA 367 kb), with 90% also acquiring conjugative mobile genetic elements (MGE) from the donor. We showed that individual conjugative plasmids, and integrative conjugative elements (ICE), from donors were sufficient to drive hybrid formation. These observations strongly support conjugative chromosomal DNA transfer as the major mechanism underlying hybrid formation. ICE are genome-integrated and passively propagated but when transferring to recipients they normally do so by excising and producing their own conjugation machinery. We found that ICE were responsible for the highest frequencies of hybrid chromosome formation. They could mobilize DNA around the full length of the chromosome, including the simultaneous acquisition of mutant variants of gyrA and parC, separated by ∼826 kb, generating highly fluoroquinolone-resistant bacteria in a single event. Bacterial hybrid chromosome formation driven by conjugative MGE may be an important and widespread mechanism in the emergence and evolution of high-risk bacterial pathogens.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13127887/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147639293","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":"Forecasting Multitrait Resistance Evolution under Antibiotic Stress.","authors":"Suvam Roy, Eric Libby, Peter A Lind","doi":"10.1093/molbev/msag065","DOIUrl":"10.1093/molbev/msag065","url":null,"abstract":"<p><p>Many bacteria rely on efflux pumps to survive antibiotic stress and exposure to antibiotics often leads to mutations in pump genes or their regulators that increase pump expression. Predicting the spectrum of these mutations is important for designing effective antibiotic treatments, but the underlying regulatory networks are large and complex, making them difficult to map experimentally. To address this challenge, we developed a mathematical framework that integrates dynamical equations for efflux pump regulation with a genetic algorithm for parameter estimation and evolutionary simulations. Using this framework, we simulated in silico evolution of Pseudomonas aeruginosa under exposure to the antibiotics meropenem, tobramycin, and ciprofloxacin. The simulations revealed mutational spectra affecting the expression of four Resistance-Nodulation-Division efflux pumps and their shared regulatory network. The most frequently mutated genes were single-target regulators that matched well with previous observations in clinical and in vitro studies. The model also showed that the shared use of the OprM protein by two pumps is a key factor shaping their distinct mutational patterns. Mutations often produced multitrait phenotypes, manifesting as collateral sensitivity or cross-resistance to antibiotics not used for selection. While cross-resistance evolved readily, its extent depended on initial pump expression levels and thus may vary between strains. Finally, simulations of changing environments showed that efflux pump genes tend to be lost in the absence of antibiotics, suggesting a potential strategy to steer bacterial evolution toward reduced capacity to re-evolve resistance.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":5.3,"publicationDate":"2026-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13049199/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147444353","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}