{"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}
Brice Letcher, Lewis Stevens, Nathanaëlle Saclier, Andrew Hsiao, Manuela Kieninger, Eva Wenger, Caroline Launay, Mark Blaxter, Marie Delattre
{"title":"Emergence and stabilization of a neo-Y chromosome in nematode species with rare males.","authors":"Brice Letcher, Lewis Stevens, Nathanaëlle Saclier, Andrew Hsiao, Manuela Kieninger, Eva Wenger, Caroline Launay, Mark Blaxter, Marie Delattre","doi":"10.1093/molbev/msag177","DOIUrl":"10.1093/molbev/msag177","url":null,"abstract":"<p><p>How do sex chromosomes evolve in the transition to asexuality? So far, species that depart from canonical sexual reproduction-for example, parthenogens with rare sex or species where the paternal genome is set aside-have been found to carry either no sex chromosomes or sex chromosomes but no male-specific sex chromosome (i.e. no Y). Here we reveal that, in Mesorhabditis nematodes, a new Y chromosome evolved once, from sexual ancestors, in species that have transitioned into an unconventional mode of reproduction called autopseudogamy. In this reproductive system, females produce clonal females plus rare (∼10%) males that are needed for fertilization but that do not contribute to the female genome. Analyzing the Y chromosomes of two autopseudogamous species, we found high levels of degeneration, most likely due to loss of recombination, and two additional conserved features: (i) they accumulated male-beneficial genes, and (ii) they display a strong fertilization drive, in that mainly Y-bearing sperm fertilize female oocytes. Both features are likely evolutionarily favorable in the context of autopseudogamy. Our results suggest that male-specific chromosomes can still be maintained in systems with rare, and possibly \"genetically useless,\" males.</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/PMC13511141/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148549610","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":"Parasites constrain within-population diversification while accelerating between-population divergence in an RNA replication system.","authors":"Yuki Kanai, Norikazu Ichihashi","doi":"10.1093/molbev/msag184","DOIUrl":"10.1093/molbev/msag184","url":null,"abstract":"<p><p>Diversification of replicators from simple self-replicating RNA molecules is a major challenge in prebiotic evolution. In our previous evolution experiment using an RNA replication system derived from the Qβ phage, a single RNA species spontaneously diversified into multiple coexisting host and parasite RNA lineages through arms race dynamics, suggesting that host-parasite interactions may promote diversification in molecular replicator ecosystems. To test this idea more directly, we evolved six independent RNA populations under high-parasite and low-parasite conditions. High-parasite populations showed accelerated mutation fixation and greater sequence divergence between populations. However, contrary to expectation, host diversification within populations was limited under high-parasite conditions, whereas transient diversification into at most three host lineages occurred under low-parasite conditions. Sequence and biochemical analyses indicate that this diversification was consistent with relaxed selection among host RNAs that achieved similar replication yields under compartmentalized replication. In contrast, coexistence with parasites helped maintain high replication capacities by continuously imposing selection for improved replication. These results suggest that antagonistic host-parasite interactions help maintain functional activity and promote divergence between populations while constraining diversification within populations. Such opposing effects may have shaped the balance between functional optimization and diversification during early molecular evolution.</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/PMC13440312/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148562537","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}
Attila Placido Sachslehner, Julia Steinbinder, Anja Wagner, Klaus Kratochwill, Leopold Eckhart
{"title":"Evolution of an amphibian-specific family of epidermal differentiation-associated genes.","authors":"Attila Placido Sachslehner, Julia Steinbinder, Anja Wagner, Klaus Kratochwill, Leopold Eckhart","doi":"10.1093/molbev/msag196","DOIUrl":"10.1093/molbev/msag196","url":null,"abstract":"<p><p>The surface layer of the skin and hard skin appendages of land-dwelling vertebrates depend on epithelial differentiation-associated proteins, which increase the mechanical resilience of cells upon cornification. These proteins, exemplified by keratin-associated proteins (KRTAPs) in mammals and epidermal differentiation complex (EDC) proteins in all tetrapods, have low amino acid sequence complexity and interact with other proteins to form stable supramolecular structures. No KRTAPs and only few EDC proteins exist in amphibians, suggesting an alternative mechanism of epithelial cornification. Here, we used comparative genomics and proteomics to identify a previously uncharacterized group of epidermal differentiation-associated proteins that are specific for amphibians. These proteins are encoded by genes of the amphibian epidermal differentiation cluster (AEDC), which has evolved by tandem duplications and sequence modifications of an ancestral gene at a locus syntenic with that of adipogenesis regulatory factor in other vertebrates. AEDC genes are specifically expressed in the epithelium of the skin and its appendages, such as the cornified spines within nuptial pads of frogs. Internal sequence duplications within AEDC proteins have led to amino acid sequence repeats similar to those of EDC proteins and KRTAPs. We conclude that epidermal differentiation-associated proteins have originated multiple times and evolved similar sequence features in amphibians and other clades of vertebrates.</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/PMC13487633/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148679165","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}
Mohammad A Siddiq, Hannah P Kania, Nicholas J Brown, Patricia J Wittkopp
{"title":"Cis- and trans-regulatory factors contributing to divergent activity of the TDH3 promoter in Saccharomyces yeast.","authors":"Mohammad A Siddiq, Hannah P Kania, Nicholas J Brown, Patricia J Wittkopp","doi":"10.1093/molbev/msag203","DOIUrl":"10.1093/molbev/msag203","url":null,"abstract":"<p><p>Changes in regulatory sequences controlling the timing and activity of gene products underlie much of natural phenotypic variation. Yet, identifying which divergent sites matter and how they impact gene expression remains challenging. Here, we investigate how transcriptional activity and homeostatic responsiveness of orthologous promoters of the metabolic gene TDH3 evolved among Saccharomyces yeast. We found that promoter expression level increased specifically in the Saccharomyces cerevisiae lineage and that a substantial part of this increase was caused by genetic variants located between the well-characterized, conserved binding sites for two direct transcriptional regulators. These nucleotide changes altered the promoters' expression levels while leaving the expression dynamics conserved. Further, the effects of these nucleotide changes were only seen in the presence of a third transcription factor, TYE7p, which is known to be recruited by the other transcription factors through protein-protein interactions. These results suggest that the cis-regulatory changes act through their influence on the collective assembly/activation of a transcription factor complex and that changes acting through such a mechanism can allow distinct parts of gene expression, such as expression level and dynamics, to separately diverge.</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/PMC13520121/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148725130","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Correction to: Efficient Estimation of Nucleotide Diversity and Divergence Using Callable Loci (and More).","authors":"","doi":"10.1093/molbev/msag192","DOIUrl":"10.1093/molbev/msag192","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/PMC13455008/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148701829","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":"Epistatic impacts of cis- and trans-regulatory mutations on the distribution of mutational effects for gene expression in Saccharomyces cerevisiae.","authors":"Eden McQueen, Bing Yang, Patricia J Wittkopp","doi":"10.1093/molbev/msag172","DOIUrl":"10.1093/molbev/msag172","url":null,"abstract":"<p><p>Epistasis can influence evolution by causing the distribution of phenotypic effects for new mutations to vary among genotypes. Here, we investigate how epistatic interactions between new mutations and an existing regulatory mutation might impact the evolution of gene expression using Saccharomyces cerevisiae. We do so by estimating the distribution of mutational effects for expression of a fluorescent reporter protein driven by the S. cerevisiae TDH3 promoter in a reference strain as well as in eight mutant strains. Each of the mutant strains differed from the reference strain by a single mutation affecting expression of the focal gene. We found that two of these regulatory mutations changed the degree of mutational robustness, as measured by the variance of the distribution of mutational effects, with one initial regulatory mutation increasing mutational robustness while another decreased it. We also found that four of our initial regulatory mutants caused a change in the relative frequency and/or effect size of mutations increasing or decreasing expression, as measured by a change in skewness relative to the reference. Strikingly, in all four of these cases, the change in skewness increased the likelihood that new mutations would at least partially compensate for the effects of the initial regulatory mutation. If this form of epistatic impact on the distribution of mutational effects is common, it should increase the fixation probability of compensatory mutations affecting traits under stabilizing selection and could help explain the prevalence of alleles with compensatory effects in natural populations of S. cerevisiae.</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/PMC13447094/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471679","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}
Brandon S Gaut, Stephen I Wright, Tianpeng Wang, Peter L Morrell
{"title":"What has population genomics told us about the dynamics of selection and plant adaptation?","authors":"Brandon S Gaut, Stephen I Wright, Tianpeng Wang, Peter L Morrell","doi":"10.1093/molbev/msag171","DOIUrl":"10.1093/molbev/msag171","url":null,"abstract":"<p><p>Population genomics has transformed our understanding of how natural selection shapes plant genomes. The explosion of whole-genome resequencing data has enabled estimates of nucleotide diversity across genomes, clarified how selection interacts with recombination and demography, and broadened inference beyond crops and model species to virtually any plant system. Here, we synthesize key lessons and outstanding challenges concerning the action of natural selection on plant genomes. One message is that purifying selection is a pervasive selective force acting against deleterious mutations and structural variants, but its efficacy varies predictably and is often relaxed after demographic contractions, including domestication bottlenecks, range expansions, shifts in mating systems, and polyploid formation. Adaptation also routinely shapes genetic diversity, as evidenced by the detection of selective sweeps. Swept genes have functional biases, but many outstanding questions about adaptive variation remain, including the selection coefficients of adaptive alleles, whether selection typically acts on segregating variants or de novo mutations, and how often selection is polygenic. As with polygenic selection, our knowledge about balancing selection is limited, due in part to challenges in its detection. It is known, however, to act on disease-resistance genes and genes that govern breeding systems. Finally, an emerging theme in plant population genomics is the interplay between introgression and adaptation, but it remains challenging to link introgression confidently to fitness, and further study requires an expanded, multispecies scale. This review reveals the power, and some of the limits, of population genomics to infer the dynamics of selection on plant genomes.</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/PMC13455019/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148471699","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}
Andrew L Wheeler, Chiragdeep Chatur, Peter W Goodman, Robert C Edgar, Gavin A Huttley, Joanna Masel
{"title":"Improved gene tree inference from removing alignment errors both from focal genes and when training substitution models.","authors":"Andrew L Wheeler, Chiragdeep Chatur, Peter W Goodman, Robert C Edgar, Gavin A Huttley, Joanna Masel","doi":"10.1093/molbev/msag182","DOIUrl":"10.1093/molbev/msag182","url":null,"abstract":"<p><p>Multiple sequence alignment (MSA) is a key step in phylogenetic analysis and is prone to error. Unfortunately, algorithms that remove likely alignment errors from MSAs sometimes also remove informative residues, making phylogenetic tree inference worse. Here we present a novel MSA cleaning algorithm based on consensus between MSAs using a range of Hidden Markov Models and guide trees, named CLOAK (CLeaning On the basis of Alignment C(K)onsensus). CLOAK is a gentle filter, with a low false positive rate for removal from MSAs according to the BALiBASE benchmarks, while still removing a significant fraction of likely alignment errors. Gentle vs. stringent MSA filtering methods are appropriate for different tasks. We assess methods based on their ability to bring the gene trees of single copy orthologs closer to the accepted species tree. Amino acid substitution models trained on filtered MSAs improve gene tree inference, with stricter filtering methods providing the biggest model improvements. In contrast, it is gentler filtering of single gene MSAs that provides additional improvements to gene tree inference, with CLOAK performing best.</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/PMC13449614/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"148592697","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}