Molecular biology and evolution最新文献

{"title":"Multiscale structural evolution of proline-rich protein genes shapes primate salivary defenses.","authors":"William D Aguado, Charikleia Karageorgiou, Sarah Kassem, Raquel Hernandez Rojas, Carrie C Veilleux, Amanda D Melin, Erin R Vogel, Stefan Ruhl, Omer Gokcumen, Petar Pajic","doi":"10.1093/molbev/msag224","DOIUrl":"https://doi.org/10.1093/molbev/msag224","url":null,"abstract":"<p><p>Saliva forms the first biochemical interface with the environment, mediating dietary exposure and oral defense. Proline-rich proteins (PRPs) in saliva protect plant-eating mammals from the harmful effects of consuming tannins. Yet the evolution of the genes encoding these proteins remains poorly resolved. Here, integrating long-read genome assemblies with comparative genomics, phylogenetics, transcriptomics, and dietary data, we investigate the salivary PRP gene family across 27 primate species to test whether dietary ecology has shaped the evolution of this locus. We find that the PRP locus is dynamic, shaped by recurrent lineage-specific gene duplications and inversions. Despite pervasive structural variation, PRP genes consistently rank among the top five most highly expressed transcripts in non-human primate parotid glands, indicating constraint on maintaining high expression in saliva. Humans retain abundant PRP expression, but at reduced levels relative to other primates, potentially reflecting a lineage-specific regulatory shift. We further identify widespread exonic tandem repeats that provide a flexible mechanism for modulating protein composition. Notably, colobine PRH genes independently evolved trinucleotide repeats encoding histidine-rich peptides, coinciding with folivory and suggesting a lineage-specific adaptation. Together, our results position PRPs as a model for understanding how large-scale structural rearrangements and fine-scale repeat expansions jointly shape the diversity and evolution of proteins in saliva.</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":"148865745","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":"No genome-wide correlations and little shared genetic architecture between reproductive life-history traits and estrogen receptor-positive breast cancer risk.","authors":"Euan A Young, E Yagmur Erten, Erik Postma, Virpi Lummaa, Bert van der Vegt, Geertruida H de Bock, Hannah L Dugdale","doi":"10.1093/molbev/msag222","DOIUrl":"https://doi.org/10.1093/molbev/msag222","url":null,"abstract":"<p><p>Estrogen receptor-positive breast cancer (ER+ BC) is one of the most prevalent cancers, but the evolutionary processes shaping genetic variation in ER+ BC risk are poorly understood. Both evolutionary life-history theory and evidence from studies of individual ER+ BC risk variants suggest that increased genetic ER+ BC risk is associated with faster maturation, earlier reproduction, and/or increased reproductive success (i.e., there is a trade-off), but it is unclear how well this pattern is replicated when considering the polygenic architecture of these traits after controlling for potential biases. Here, we estimate genome-wide genetic correlations between ER+ BC risk and three reproductive traits (age at menarche, age at first birth, and the number of children) using genomic restricted maximum-likelihood analyses on Lifelines biobank data and linkage disequilibrium score regressions on population and family-based genome-wide association study data. Regardless of the data or method used, genetic correlations were low and not statistically significant. Further analyses decomposing genome-wide genetic variance into local regions detected only three loci exhibiting significant pleiotropy between ER+ BC risk and age at menarche, suggesting little shared genetic architecture between ER+ BC risk and reproductive traits. Thus, the role of life-history trade-offs in shaping ER+ BC risk in European populations appears, at most, small, and the evolutionary processes giving rise to this life-threatening disease remain unclear. Future studies could examine the impact of evolutionary mismatches in shaping ER+ BC risk, where conducting longitudinal studies on populations transitioning to reproductive patterns observed in contemporary European populations would be most useful.</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":"148865678","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":"Pax6 homologs are required for patterning both visual systems of the daddy-longlegs Phalangium opilio.","authors":"Ethan M Laumer, Sophie M Neu, Benjamin C Klementz, Pranil Panda, Emily V W Setton, Prashant P Sharma","doi":"10.1093/molbev/msag226","DOIUrl":"https://doi.org/10.1093/molbev/msag226","url":null,"abstract":"<p><p>The evolution of visual systems has compelled numerous investigations of developmental processes underlying eye patterning across Bilateria. It is well-established that homologs of the transcription factor Pax6 play a highly conserved role in eye fate specification and are at the top of the retinal determination gene network (RDGN) hierarchy. Curiously, Pax6 homologs do not appear to maintain this function in well-studied chelicerate models. It was recently proposed that the gene Pax2 may have subsumed the role of Pax6 in eye fate specification in chelicerates. However, no functional data are available for any chelicerate Pax homologs. We examined the incidence of Pax family genes across chelicerate phylogeny, and interrogated the expression and function of Pax2 and Pax6 homologs in the daddy-longlegs Phalangium opilio, which bears a highly plesiomorphic arrangement of visual systems. We show that eyeless (ey) and twin of eyeless (toy) are expressed early in the developing head lobes of P. opilio, whereas sv is not. Gene silencing of ey, toy, and sv individually had no discernible effect on eye development. By contrast, double knockdown of ey and toy resulted in defects or loss in all three eye pairs of P. opilio. These data are consistent with a conserved role for Pax6 homologs in patterning both median and lateral visual systems across arthropods. Our results suggest that heterochronic shifts in expression, rather than changes in function, underlie the atypical dynamics of Pax genes in derived arachnid groups such as spiders.</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":"148865667","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":"Evolution of virulence of a plant RNA virus in developmental stage-structured host populations.","authors":"José L Carrasco, Christina Toft, Santiago F Elena","doi":"10.1093/molbev/msag225","DOIUrl":"https://doi.org/10.1093/molbev/msag225","url":null,"abstract":"<p><p>Natural host populations are age-structured, and developmental stages differ in susceptibility and within-host pathogen dynamics, potentially imposing distinct selective pressures on viruses. However, the evolutionary consequences of host age structure remain poorly understood. We experimentally evolved turnip mosaic potyvirus for five passages in Arabidopsis thaliana populations spanning seven demographic regimes, from juvenile- to mature-dominated cohorts. We quantified disease progression, symptom severity, and viral load, cross-inoculated evolved lineages across host stages to construct infection matrices, and performed whole-population sequencing at passages 1 and 5. Disease traits changed markedly with passage, demography, and their interaction. Disease progression evolved faster in older populations, whereas symptom severity was independent of median age, indicating demographic reweighting of virulence components. Viral load increased across passages and positively correlated with severity, linking within-host fitness to symptoms. Cross-inoculation assays revealed a modular infection network: juvenile-evolved lineages specialized on juvenile hosts, whereas lineages from intermediate and older populations were more generalist. Genomically, we detected both parallel and demography-specific adaptations, including recurrent changes in the viral protein VPg (involved in translation, replication and host interactions) as well as synonymous variants showing consistent or opposing selection across host population stage structures. Overall, host age structure emerges as a major ecological driver of virulence evolution, shaping trade-offs between disease progression and severity and determining specialization versus generalism. These results integrate phenotypic and genomic responses and suggest that manipulating crop age structure could steer virus evolution toward less damaging outcomes.</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":"148865694","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":"Disruption of mitonuclear coadaptation and compensatory evolution after an extreme dietary shift in carnivorous butterflies.","authors":"Runzhao Fang, Xiao Tian, Dan Liang, Peng Zhang","doi":"10.1093/molbev/msag221","DOIUrl":"https://doi.org/10.1093/molbev/msag221","url":null,"abstract":"<p><p>Mitochondrial function depends on tight coordination between mitochondrial and nuclear genomes, which requires long-term coevolution to maintain mitonuclear coadaptation. While mitonuclear incompatibility is typically studied in the context of hybridization, other evolutionary scenarios that may disrupt coadaptation between the two genomes remain less explored. Here, we propose that extreme ecological niche shifts may disrupt mitonuclear coadaptation, which we test in carnivorous Miletinae butterflies with an extreme dietary transition. By generating high-quality genome assemblies, we found that Miletinae exhibit extensive chromosomal rearrangements. Comparative phylogenomic analyses revealed a striking asymmetric mitonuclear evolutionary response: Miletinae exhibit elevated mitochondrial nucleotide substitution rates compared to phytophagous relatives, whereas nuclear rates remain stable. This shift reverses the typical lepidopteran pattern where nuclear rates exceed mitochondrial rates. Interestingly, this mitochondrial acceleration is driven primarily by relaxed purifying selection rather than positive selection. To sustain mitochondrial function, the nuclear genome of Miletinae underwent pervasive, multilayered compensatory evolution. We detected strong signatures of positive selection and accelerated evolution in nuclear genes directly interacting with mitochondrial components across oxidative phosphorylation (OXPHOS) complexes, the mitochondrial translation, replication and transcription machinery. Furthermore, this nuclear compensatory response extends to systems governing mitochondrial homeostasis, including protein quality control and RNA degradation and stabilization. Our results support a model in which extreme ecological transitions can disrupt ancestral mitonuclear coadaptation and promote the emergence of a new coadapted state through systemic nuclear compensation. This study broadens the conceptual framework of mitonuclear coevolution and highlights its role in facilitating evolutionary persistence after major ecological shifts.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830465","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":"Variant calling in non-model organisms with snpArcher.","authors":"Cade Mirchandani, Abdelmajid Omarjee, Guillaume Achaz, Erik Enbody, Gregg Thomas, Timothy B Sackton","doi":"10.1093/molbev/msag220","DOIUrl":"https://doi.org/10.1093/molbev/msag220","url":null,"abstract":"<p><p>Population genomic studies in non-model organisms increasingly depend on whole-genome resequencing, yet translating raw reads into reliable variant callsets remains a practical challenge due to the complexity of multi-step bioinformatics pipelines and the absence of species-specific best practices. Here we present a step-by-step protocol for snpArcher, a Snakemake-based workflow that takes raw sequencing reads and a reference genome as input and produces a filtered, joint-called VCF suitable for downstream population genomic analysis. We guide users through six phases: installation and environment setup, sample sheet creation, run configuration, execution on local or high-performance computing systems, quality control review using an interactive HTML dashboard, and downstream analysis, focusing on postprocessing and filtering. The QC dashboard aggregates individual-level metrics including principal component analysis, relatedness estimation, depth-missingness diagnostics, and admixture analysis to help identify batch effects, contamination, cryptic relatedness, and outlier samples before downstream analysis. We demonstrate the impact of sequential filtering steps on the site frequency spectrum and demographic inference using a dataset of 137 burrowing owl (Athene cunicularia) genomes, showing how removal of low-coverage individuals, sex-linked scaffolds, and regions of excess heterozygosity eliminates artifacts that would otherwise bias inference of population size history. This protocol is intended as a practical companion to the original snpArcher publication, enabling researchers working with non-model organisms to produce and evaluate analysis-ready variant callsets in a reproducible manner.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148830519","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":"Consistent and idiosyncratic pleiotropy in shaping genetic correlations.","authors":"Haoran Cai, Kerry Geiler-Samerotte, David L Des Marais","doi":"10.1093/molbev/msag215","DOIUrl":"https://doi.org/10.1093/molbev/msag215","url":null,"abstract":"<p><p>Pleiotropy, the phenomenon where a single mutation influences multiple phenotypic traits, creates genetic correlations that can constrain evolutionary trajectories. Yet genetic correlations differ in their persistence: some remain stable over long evolutionary timescales, whereas others change rapidly across generations or environments. One explanation is that similar values of genetic correlation, rG, can arise from different pleiotropic architectures: broadly aligned effects across many loci, or disproportionate covariance contributions from a few large effect loci. Motivated by the distinction between vertical and horizontal pleiotropy, here, we develop a bivariate marker effect framework for recombinant mapping populations that separates candidate large covariance contributors from the polygenic background correlation, rD. We define rD as the correlation among marker effects after trimming markers with unusually large covariance contributions. rD is a trait-pair summary of how consistently small and moderate effect markers align across the genome; high rD is expected when many perturbations propagate through shared developmental, physiological, causal, or geometric structure. Applying this framework to high-dimensional yeast single-cell morphology, we show that trait pairs with similar rG can differ substantially in rD, and that a small number of candidate outlier regions can strongly influence some marker effect correlations. We then test whether rD predicts the environmental stability of genetic correlations under geldanamycin-mediated Hsp90 perturbation. Trait pairs with stronger rD show smaller absolute changes in rG. These results suggest that genetic correlations supported by a strong polygenic marker effect background are more environmentally stable than correlations shaped primarily by a few large covariance contributors.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148795372","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":"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":"https://doi.org/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":"2026-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"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, in which small subsamples of sites from a concatenated alignment are expanded by upsampling before inference, and the resulting analyses are then 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, while reducing runtime and memory requirements by orders of magnitude. 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. Automated tuning of subsample size, the number of subsamples, and the number of upsampling replicates make PSU practical across diverse datasets. We suggest that PSU is a general strategy 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":"2026-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","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":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Regulatory activity and evolutionary co-option of cis-regulatory elements underlying bear hibernation.","authors":"Blair W Perry, Kara Ryan, Kerry L McGowan, T Brock Wooldridge, Marina Savenkova, Sascha H Duttke, Heiko T Jansen, Charles T Robbins, Joanna L Kelley","doi":"10.1093/molbev/msag193","DOIUrl":"https://doi.org/10.1093/molbev/msag193","url":null,"abstract":"<p><p>Uncovering the regulatory architectures that underlie complex phenotypes can provide insight into both the mechanisms and evolution of unique adaptations. In bears, thousands of genes are differentially expressed in a tissue-specific manner during hibernation, many of which are involved in major vertebrate metabolic signaling pathways. However, the precise regulatory mechanisms driving these gene expression changes, and the extent of their conservation in non-hibernating mammals, remain poorly understood. Using capped-small RNA-sequencing from brown bear adipose tissue, we identify putative enhancers that exhibit dynamic shifts in regulatory activity during hibernation. The majority of these enhancers share sequence homology with known human enhancers, yet many appear to target distinct genes, suggesting a role of regulatory co-option in the evolution of hibernation. Using these newly identified enhancers, we identify transcription factors putatively underlying hibernation gene expression, expanding our mechanistic understanding of hibernation physiology. Additionally, we find evidence for selection on cis-regulatory sequences associated with physiological adaptation across bears. Collectively, this study provides new perspectives on the mechanisms and evolution of mammalian hibernation, and the roles of regulatory sequences in the evolution of complex physiological adaptations.</p>","PeriodicalId":18730,"journal":{"name":"Molecular biology and evolution","volume":" ","pages":""},"PeriodicalIF":6.4,"publicationDate":"2026-08-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701850","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}