Molecular Biology And Evolution[JOURNAL]
Sun
200 papers
The life history of recessive deleterious alleles as seen through the eyes of a honey bee (Apis mellifera).
Shultz RR, Nixon JM, Ryals DK … +11 more , Buschkoetter AC, Gilchrist IR, Krispn Given J, Metz BN, Magaña AA, Moon KM, Thanepohn B, Mahood J, Tarpy DR, Foster LJ, Harpur BA
Mol Biol Evol · 2026 Jul · PMID 42393836 · Publisher ↗
Deleterious mutations arise continually in natural populations, yet their full life histories-from origin to elimination-are rarely observed directly. Most understanding of mutational fate in the wild comes from indirect...
Deleterious mutations arise continually in natural populations, yet their full life histories-from origin to elimination-are rarely observed directly. Most understanding of mutational fate in the wild comes from indirect inference rather than from tracking a single mutation through time and space. Haplodiploid systems provide a rare opportunity to observe negative selection in action: because males are haploid, recessive alleles are immediately exposed to selection rather than masked by heterozygosity. Haplodiploidy has long been hypothesized to accelerate the purging of deleterious variation. Here, we leverage the honey bee as a model system to document the complete trajectory of a spontaneous deleterious mutation, from its origin in a single queen to its extinction. The mutation alters eye pigmentation in haploid males, enabling us to quantify its molecular, physiological, and behavioral consequences through integrated genomic, transcriptomic, proteomic, and metabolomic analyses. By following this mutation across generations, we directly observe how haplodiploidy exposes recessive alleles to immediate purifying selection, and how mating structure and colony demography influence their persistence. This study represents one of the few documented cases of a naturally occurring mutation tracked through its full evolutionary course, offering a rare empirical view of how selection operates in real time within a social, haplodiploid genome.
Severe bottleneck of ancient Homo populations: Insights from computational modeling and relevant fossil evidence.
Zhou S, Zhou Y, Di Vincenzo F … +6 more , Manzi G, Hu W, Hao Z, Shao Z, Pan YH, Li H
Mol Biol Evol · 2026 Jul · PMID 42391510 · Publisher ↗
Reconstructing ancient population size history is essential for understanding the evolutionary origin of Homo sapiens. We recently developed the fast infinitesimal time coalescent process (FitCoal) and detected a severe...
Reconstructing ancient population size history is essential for understanding the evolutionary origin of Homo sapiens. We recently developed the fast infinitesimal time coalescent process (FitCoal) and detected a severe population bottleneck occurring approximately 930 thousand years ago. However, two recent studies compared FitCoal and mushi and concluded that the severe bottleneck is a statistical artifact. In this study, we compared the two methods against a benchmark of ten billion msprime coalescent simulations. We demonstrate that FitCoal achieves both superior speed and accuracy in expected site frequency spectrum (SFS) estimation. Analyses of simulated datasets confirmed that FitCoal reliably recovers the bottleneck, whereas mushi fails under identical conditions. Independent fossil and paleoclimate evidence is consistent with the timing and evolutionary impact of this bottleneck, including associations with hominin dispersals, speciation events, and a subsequent increase in brain size. These findings refine the demographic history of Homo during the Pleistocene and highlight the importance of high-precision SFS computation for revealing critical evolutionary transitions that shaped modern human ancestry.
Population Epigenetics: Deciphering DNA Methylation Diversity and its Implications for Health, Disease, and Evolution.
Cheng S, Xu S
Mol Biol Evol · 2026 Jul · PMID 42390000 · Publisher ↗
Population epigenetics investigates the distribution, determinants, and evolutionary significance of epigenetic variation, particularly DNA methylation (DNAm), within and among human populations. In this review, we synth...
Population epigenetics investigates the distribution, determinants, and evolutionary significance of epigenetic variation, particularly DNA methylation (DNAm), within and among human populations. In this review, we synthesize recent advances in population epigenetics with an explicit evolutionary perspective, focusing on three interconnected dimensions. First, we outline patterns of DNAm variation, including tissue- and cell-, and developmental-stage specificity. Second, we examine the sources of DNAm variation, highlighting population-specific methylation quantitative trait loci, ancestry-related genetic architecture, and environmental modulators such as diet, climate, pollution, and lifestyle. Third, we explore evolutionary and clinical implications, linking DNAm variation to phenotypic plasticity, disease susceptibility, and adaptive processes shaped by natural selection. Comparative population studies demonstrate that genetic ancestry accounts for a substantial proportion of DNAm differentiation, reflecting the joint effects of allele-frequency divergence, linkage disequilibrium structure, and demographic history. At the same time, environmentally induced methylation changes introduce a dynamic and rapidly responsive layer of molecular diversity that can mediate short-term adaptation to local environments. Despite rapid progress, key challenges remain, including disentangling genetic, environmental, and technical confounders, assessing the stability and heritability of population-specific DNAm patterns, and establishing causal links between methylation, fitness-related traits, and selection. Looking ahead, advances in large-scale multi-ancestry cohorts, single-cell and long-read epigenomics, and integrative multi-omics will enable high-resolution mapping of epigenetic variation across populations. By bridging evolutionary theory, epigenetic epidemiology, and functional genomics, population epigenetics offers a powerful framework for understanding human adaptation, health disparities, and precision medicine in an evolutionary context.
Genomic signature of repeated transitions to diurnality in spiders.
Tong C, Fan Z, Wang L … +1 more , Zhang Z
Mol Biol Evol · 2026 Jul · PMID 42389982 · Publisher ↗
Repeated transitions to diurnality represent a major behavioral shift in spiders, yet their genomic underpinnings remain largely unknown. Here, we assembled high-quality genomes for nine diurnal spiders using long-read s...
Repeated transitions to diurnality represent a major behavioral shift in spiders, yet their genomic underpinnings remain largely unknown. Here, we assembled high-quality genomes for nine diurnal spiders using long-read sequencing and compiled diel activity phenotypic data through a combination of systematic literature synthesis and field assessments. By integrating all publicly available spider genomes, we examined the genomic evolutionary dynamics of 67 species including at least 5 independent origins of diurnality. Across diurnal spider lineages, hundreds of genes exhibited convergent shifts in selection, including intensified selection on neural, locomotion, and visual system genes, and relaxed selection on several core phototransduction components. Notably, diurnal spiders showed convergent deceleration in evolutionary rates in circadian regulators, such as CLOCK and CRTC1, and they harbored distinct repertoires of positively selected genes relative to non-diurnal species. In addition, convergent amino acid substitutions were enriched in diurnal hunting spiders. Comparative multi-tissue transcriptomics showed that genes under convergent selection, particularly those involved in vision, sensory processing, nervous system development, and locomotion, tended to exhibit stronger eye- and central nervous system-biased tissue specificity in diurnal species. Altogether, our results reveal convergent genomic changes associated with repeated evolution of diurnality and illustrate how ecological light environments repeatedly shape the molecular evolution of complex animal behavior.
Phylogenomic blind spots: The limits of UCE and BUSCO loci in the presence of gene flow.
Foley NM, Murphy WJ
Mol Biol Evol · 2026 Jun · PMID 42366789 · Publisher ↗
Ultraconserved elements (UCEs) and BUSCO genes are commonly used markers in reduced-representation phylogenomic studies. They are valued for their evolutionary conservation, ease of alignment, and cost-effectiveness in g...
Ultraconserved elements (UCEs) and BUSCO genes are commonly used markers in reduced-representation phylogenomic studies. They are valued for their evolutionary conservation, ease of alignment, and cost-effectiveness in generating phylogenomic datasets for non-model species. Recombination-aware phylogenomic approaches reveal that, with increased historical and recent gene flow, the species tree may be limited to genomic regions with low recombination rates, whereas introgression-associated alleles are most often found in high-recombining regions. In this study, we aimed to determine whether widely used UCE and BUSCO datasets can reliably recover the species tree in mammalian clades where extensive introgression has previously been documented using recombination-aware methods. Our analyses indicate that UCEs and BUSCO loci are not sampled randomly from the genome and are underrepresented in mammalian sex chromosomes and other low-recombining genomic regions. Concatenation and coalescent-based phylogenomic analyses across 12 clades with varying degrees of gene flow showed that UCEs and BUSCO datasets do not recover the true species topology when introgression is frequent. Although neutral loci are generally preferred for phylogenomic analyses, per-base constraint measures estimated genome-wide show that UCE and BUSCO loci originate from genomic regions under very strong selective constraint. Comparisons of branch lengths and node heights from trees based on accelerated, neutral, and conserved PhyloP datasets revealed that those derived from UCE and BUSCO data are compressed relative to trees from neutral regions. We conclude by proposing mitigation strategies to address some of the issues identified in this study, thereby improving the use of UCE-based or other target-enrichment methods in phylogenomics.
seqLens: Optimizing Language Models for Genomic Predictions.
Baghbanzadeh M, Mann BT, Crandall KA … +1 more , Rahnavard A
Mol Biol Evol · 2026 Jul · PMID 42342250 · Full text
Understanding evolutionary variation in genomic sequences through the lens of language modeling has the potential to revolutionize biological research. Yet to maximize the utility of language modeling in genomics, we mus...
Understanding evolutionary variation in genomic sequences through the lens of language modeling has the potential to revolutionize biological research. Yet to maximize the utility of language modeling in genomics, we must overcome computational challenges in tokenization and model architecture adapted to diverse genomic features across evolutionary timescales. In this study, we investigated key elements in genomic language modeling (gLM), including tokenization, pretraining datasets, fine-tuning approaches, pooling methods, and domain adaptation, and applied the language models to diverse genomic data. We gathered two evolutionarily distinct pretraining datasets: one consisting of 19,551 reference genomes, including over 18,000 prokaryotic genomes (115 B nucleotides) and the remainder eukaryotic genomes, and another more balanced dataset with 1,354 genomes, including 1,166 prokaryotic and 188 eukaryotic reference genomes (180 B nucleotides). We trained five byte-pair encoding tokenizers and pretrained 52 gLMs, systematically comparing different architectures, hyperparameters, and classification heads. We introduce seqLens, a family of models based on disentangled attention with relative positional encoding, which outperforms relatively similar-sized models in 13 of 19 benchmarking phenotypic predictions. We further explore continual pretraining, domain adaptation, and parameter-efficient fine-tuning methods to assess trade-offs between computational efficiency and accuracy. Our findings demonstrate that relevant pretraining data significantly boost performance, alternative pooling techniques can enhance classification, tokenizers with larger vocabulary sizes negatively impact generalization, and gLMs are capable of understanding evolutionary relationships. These insights provide a foundation for optimizing genomic language models for identifying diverse evolutionary genomic features and improving genome annotations.
The transcriptional and translational outcomes for pseudogenes in bacterial endosymbionts.
Garber A, Nwachukwu J, Stikeleather R … +2 more , York C, McCutcheon JP
Mol Biol Evol · 2026 Jun · PMID 42334427 · Publisher ↗
Intracellular bacteria in the early stages of host adaptation often show extraordinarily disrupted genomes, where up to half of their ancestral genes are found in a pseudogenized state. The mealybug Pseudococcus longispi...
Intracellular bacteria in the early stages of host adaptation often show extraordinarily disrupted genomes, where up to half of their ancestral genes are found in a pseudogenized state. The mealybug Pseudococcus longispinus hosts two bacterial endosymbionts with high pseudogene loads, Symbiopectobacterium endolongispinus and Sodalis endolongispinus. Here, we measure transcript abundance, ribosome-associated RNA, and protein abundance in these bacterial symbionts to understand how bacteria avoid (or fail to avoid) accumulating large amounts of non-functional RNAs and proteins from these pseudogenes. Consistent with previous work, we show that pseudogene transcripts remain detectable, but at lower levels compared to those from intact and functional genes, and that relatively few pseudogenes yield detectable proteins in proteomic data. However, we find that many pseudogene transcripts still bind to Symbiopectobacterium ribosomes, and uncover a possible role for the tmRNA ribosome rescue system in the targeting of pseudogene proteins for degradation. Our results suggest a possible mechanism by which bacterial endosymbionts remove aberrant pseudogene-derived proteins during the critical time when many pseudogenes have formed but not enough time has passed for sequence evolution to erode ribosome binding sites from pseudogene transcripts.
800 million years of co-evolution in the green plant lineage - the case of LEUNIG and SEUSS transcriptional co-regulators.
Garrecht J, Rössner C, Sreechakram VNS … +4 more , Li Q, Braun S, Golz JF, Becker A
Mol Biol Evol · 2026 Jun · PMID 42333806 · Publisher ↗
The evolution of land plants has involved significant restructuring and expansion of gene networks responsible for developmental processes, leading to the emergence of new gene expression and protein interaction patterns...
The evolution of land plants has involved significant restructuring and expansion of gene networks responsible for developmental processes, leading to the emergence of new gene expression and protein interaction patterns. The LEUNIG (LUG) and SEUSS (SEU) families of transcriptional co-regulators play crucial roles in angiosperm sexual reproduction, and in developmental and environmental response pathways. These proteins often function together in widely pleiotropic actions and are central members of larger transcription-regulating complexes, interacting with various proteins, such as floral homeotic MADS-box transcription factors. However, the origins and evolution of interaction networks of these gene families remain poorly understood. To systematically address this knowledge gap, we conducted a comprehensive analysis integrating phylogeny reconstruction, protein domain analysis, and protein interaction studies across a broad range of streptophyte algae and land plants. Our findings demonstrate that the LUG and SEU genes have existed for at least 800 million years, with specific domains remaining nearly invariant. Protein interaction analyses reveal that LUG- and SEU-like proteins physically interact in streptophyte algae and across all land plant lineages. Notably, the origin of their interactions with MADS-box proteins also dates to at least the streptophyte algae, highlighting the ancient and conserved roles of LUG and SEU proteins as essential components of transcriptional regulation and hubs for protein interactions. Our analysis reveals insights into the ancient origins and conserved roles of LUG and SEU family members in transcriptional regulation in algal and land plant lineages.
RNA i-motif landscapes in plant kingdom and their potential functional roles.
Yang B, Li Y, Yan Z … +5 more , Li Y, Guneri D, Waller ZAE, Ding Y, Zhang H
Mol Biol Evol · 2026 Jun · PMID 42318932 · Full text
Nucleotide composition has evolved in patterns that reflect both phylogenetic divergence and environmental adaptation. In plants, our previous analysis of transcriptomes from the 1000 Plants (1KP) initiative revealed tha...
Nucleotide composition has evolved in patterns that reflect both phylogenetic divergence and environmental adaptation. In plants, our previous analysis of transcriptomes from the 1000 Plants (1KP) initiative revealed that nucleotide frequencies are significantly associated with habitat temperatures, suggesting selective pressures on RNA sequence and structure. Such pressures may promote the emergence of specific non-canonical RNA motifs, exemplified by G-rich RNA G-quadruplexes, which have been implicated in plant environmental adaptation. Whether similar evolutionary selection operates on other nucleotides and RNA structural motifs, however, remains unclear. Here, we investigate the evolutionary landscape of the RNA i-motif (iM), a C-rich non-canonical RNA structure, across the plant kingdom. Using iM-Seeker, we systematically identified RNA iMs and uncovered a pronounced enrichment within 5' untranslated regions (5'UTRs), with monocots exhibiting the highest iM abundance among major plant lineages. Integration of ecological variables with iM densities revealed that species from warmer environments preferentially harbor increased numbers of 5'UTR iMs, a trend most evident in monocots. Our translatome analyses in rice, wheat, tomato, and maize further indicate that 5'UTR iMs are generally associated with translational repression. Consistently, experimental validation using orthologous monocot 5'UTRs confirmed that RNA iMs are capable of repressing translation. Together, these findings reveal evolutionary selection on nucleotide composition and RNA structural motifs, highlight the adaptive significance of RNA i-motifs, and suggest that plants may use i-motifs as molecular signatures to facilitate environmental adaptation during evolution.
Functional Divergence and Structural Changes of class IV Histone Deacetylases (HDACs) Across the Tree of Life.
Nováková Z, Bartošová-Sojková P, Kudláčová J … +21 more , Baselious F, Kutilová Z, Jaklová P, Meleshin M, Motlová L, Schenkmayerova A, Vrkoslav V, Strnad Š, Horáček N, Gruber A, Žáček P, Kroll S, Havlínová B, Ondráková M, Tučková R, Krunclová T, Cvačka J, Oborník M, Schutkowski M, Sippl W, Bařinka C
Mol Biol Evol · 2026 Jun · PMID 42308148 · Full text
Class IV histone deacetylases (HDACs) are the least understood branch of the classical zinc-dependent HDAC family with HDAC11 standing out as the sole member of class IV HDACs. Using a broad phylogenetic dataset spanning...
Class IV histone deacetylases (HDACs) are the least understood branch of the classical zinc-dependent HDAC family with HDAC11 standing out as the sole member of class IV HDACs. Using a broad phylogenetic dataset spanning bacteria, archaea, and eukaryotes, we identified two deeply conserved HDAC11 lineages, clades A and B, that differ in evolutionary origin, predicted subcellular localization, and enzymatic properties. Clade A is enriched in phototrophic eukaryotes and targeted to mitochondria or plastids, whereas clade B predominates in heterotrophs and localizes mainly to the cytoplasm or nucleus. High-resolution crystal structures of selected representatives from each clade revealed a conserved catalytic core but distinct structural features-including electrostatic surface profiles, loop architectures, and foot-pocket geometries-that clearly separate the two lineages and act as sequential "selectivity filters" shaping substrate specificity. Biochemical assays show robust long-chain fatty-acid deacylase activity in clade B enzymes, but no detectable activity for any of clade A representatives against peptide substrates, suggesting adaptation to alternative, non-peptidic targets. Together, these findings define a revised evolutionary framework for HDAC11 and provide structural and functional insights into the diversification of this ancient enzyme family.
Cis-regulation of gene expression between sexes and life stages in Rumex hastatulus.
Yuan M, Sacchi BM, Choudhury BI … +3 more , Barrett SCH, Stinchcombe JR, Wright SI
Mol Biol Evol · 2026 Jun · PMID 42301149 · Full text
The potential for conflict between sexes and life stages while sharing predominantly the same genome has important evolutionary consequences. In dioecious angiosperms, genes beneficial for the haploid pollen stage may re...
The potential for conflict between sexes and life stages while sharing predominantly the same genome has important evolutionary consequences. In dioecious angiosperms, genes beneficial for the haploid pollen stage may reduce the fitness of diploid offspring of both males and females. However, we still lack an understanding of the extent of shared genetic architecture for gene expression between the sexes or life stages in plants, a key component for predicting the potential for conflict. We performed expression quantitative trait loci (eQTL) mapping to test if standing variation affects sexes and life stages differently using a population sample of the dioecious outcrossing plant Rumex hastatulus. We compared effect sizes and allele frequencies of cis-eQTLs in male and female leaf tissues and pollen and tested for genotype-by-sex interactions for gene expression. We found stronger shared genetic architecture between sexes than between life stages, suggesting greater potential for ongoing sexual conflict in leaves, which have been shown to be sexually dimorphic in earlier studies. In contrast, conflict over optimal gene expression between pollen and leaves may be easily resolved due to their distinct genetic architectures. Additionally, our burden of rare allele test suggested a signature of stabilizing selection against extreme gene expression in leaves. Our study highlights the use of eQTLs to investigate selection on gene expression and the evolution of conflict between sexes and life stages in dioecious species.
Accessible and robust machine learning approaches to improve the opsin genotype-phenotype map.
Frazer SA, Oakley TH
Mol Biol Evol · 2026 Jun · PMID 42301139 · Full text
Predicting phenotypes from genetic variation is a central challenge in biology. Here, machine learning (ML) offers great promise, but its use is often limited by poor accessibility, difficulty with interpretability, and...
Predicting phenotypes from genetic variation is a central challenge in biology. Here, machine learning (ML) offers great promise, but its use is often limited by poor accessibility, difficulty with interpretability, and a "data-cliff"-a gap between abundant sequences and scarce functional measurements. To develop more robust methods for genotype-phenotype prediction, an outstanding model system is opsin genes, visual pigments with extensive phenotypic information that strongly influence animal spectral sensitivity. Here, we advance ML characterization of the opsin genotype-phenotype map through four main contributions. First, we introduce the Opsin Phenotype Tool for Inference of Color Sensitivity, a user-friendly platform for predicting maximum wavelength sensitivity (λmax) from amino acid sequences, featuring integrated modules for SHapley Additive exPlanations and 3D structural mapping to reveal sequence-specific mechanistic drivers. Second, we show that encoding sequences with amino acid physicochemical properties improves predictive performance and interpretability over standard encoding methods and performs competitively with state-of-the-art protein language models, while retaining biological explainability. Finally, we present the Mine-N-Match pipeline, which systematically links published opsin sequences to compiled data on in vivo λmax values, expanding genotype-phenotype coverage and improving prediction, especially for undersampled taxa. By integrating accessible software, biologically informed encoding, and data harmonization, our framework improves confidence, accuracy, and interpretability of genotype-phenotype predictions for animal opsins. An accurate genotype-phenotype map will allow simulating molecular evolution of function, reconstructing the history of visual phenotypes, designing functional proteins, and generating new hypotheses that can be tested with heterologous phenotyping.
Stabilizing and directional selection shape the genetic variation of gene expression in the transcriptome of Chlamydomonas.
Balogun EJ, Sztepanacz JL, Ness RW
Mol Biol Evol · 2026 Jun · PMID 42295122 · Full text
Gene expression has proven to be a source of evolutionary novelty and is important to phenotypic evolution. However, we still have a poor understanding of the degree to which mutation contributes to variation in segregat...
Gene expression has proven to be a source of evolutionary novelty and is important to phenotypic evolution. However, we still have a poor understanding of the degree to which mutation contributes to variation in segregating and diverging populations. Here, we aim to investigate the evolutionary forces that shape the transcriptome in 24 wild strains of the green alga Chlamydomonas reinhardtii, originating from two subpopulations and four closely related species. We employ a comparative analysis of expression variation in the presence (ie genetic variance, VG) and absence (ie mutational variance, VM) of selection, in conjunction with the phylogenetic comparative model-Expression Variance Evolution, to identify the selective forces that may be shaping variation. We found that gene expression displays moderate heritability, with genetic changes accounting for 17% of the differences in expression. The transcriptome evolves under the dominant influence of stabilizing selection, with a minor role of directional selection, which was present in 7% to 14% of genes, supporting the strong conservation of expression across species that had diverged over 10 MYA. Indeed, we found that genes with high within-species variation also displayed high expression differences between species.
Multiple modes of selection underlie repeated and human-mediated adaptation in a formerly migratory fish.
Corcoran RM, Schultz ET, Velotta JP
Mol Biol Evol · 2026 Jun · PMID 42295111 · Full text
The extent to which we can predict evolution is crucial in our era of rapid anthropogenic change. Alewives (Alosa pseudoharengus) in the Atlantic coastal USA are a unique model to test for evolutionary predictability in...
The extent to which we can predict evolution is crucial in our era of rapid anthropogenic change. Alewives (Alosa pseudoharengus) in the Atlantic coastal USA are a unique model to test for evolutionary predictability in an anthropogenic context, as multiple, formerly anadromous (migratory from ocean to freshwater) populations have been independently restricted to freshwater (landlocked) by dams built in the last 350 years. Landlocked alewives show parallel changes in life history, feeding morphology, and osmoregulatory physiology. To test if recent freshwater adaptations are repeatable and predictable at the genomic level, we compared whole genomes of four landlocked and one anadromous population representing the ancestor. We determined that repeated positive selection is rare, limited to a single region on a single chromosome. Despite this, candidate analysis revealed that regions of repeatability do occur-in some populations but not others-in genes with putative function in freshwater adaptation, most notably in those involved in osmoregulation. Surprisingly, the strongest signal of selection in the genome was not one of positive selection, but one of conserved, balancing selection in a single gene family known as protocadherins, which play an important role in neural circuit formation and neuron recognition. Our results suggest that constrictive demographic histories and/or a polygenic nature of the complex trait architecture limits parallel selection at the genotypic level despite parallelism of phenotype. This highlights the need to understand both demography and trait architecture when determining the degree to which evolution is predictable.
Ancient conservation of androglobin expression reveals its evolutionary link to ciliary processes.
Osterhof C, Teschner D, Balling M … +7 more , Herwig A, Duda C, Botton-Amiot G, Hildebrandt A, Sprecher S, Hankeln T, Hoogewijs D
Mol Biol Evol · 2026 Jun · PMID 42284459 · Full text
Androglobin (Adgb) is the most distinctive member of the globin superfamily. Its characteristic globin domain is permuted, interrupted by a calmodulin-binding motif, and embedded within a large multi-domain protein of ∼1...
Androglobin (Adgb) is the most distinctive member of the globin superfamily. Its characteristic globin domain is permuted, interrupted by a calmodulin-binding motif, and embedded within a large multi-domain protein of ∼1500 amino acids that also contains a calpain protease domain. Initially described as testis-specific in mammals, Adgb is also expressed in ciliated epithelia of the female reproductive tract, lung, and brain, and knockout studies reveal its pivotal role during spermatogenesis. To trace its evolutionary origin, we performed comprehensive phylogenetic analysis across diverse eukaryotic taxa. Adgb is present in all major flagellated eukaryotic lineages but absent from non-flagellated clades. Orthology analysis indicates Adgb has been maintained as a predominantly single-copy gene across >1 billion years of evolution - a pattern contrasting sharply with other globins that underwent repeated duplication and functional diversification. Analysis of publicly available transcriptomes from early-branching metazoans confirmed robust Adgb expression in ciliated cell types and provides evidence for its regulation by the ancient ciliogenic transcription factor cRFXa in the choanoflagellate Salpingoeca rosetta. RNA in situ hybridization validated these findings, and comparative analyses suggest that ancestral Adgb homologues lacked the permuted globin domain found in metazoans. Collectively, our results demonstrate that Adgb exemplifies a rare evolutionary trajectory where structural innovation (domain permutation and fusion) enabled functional specialization while being an integral part of the non-redundant ciliary machinery. Adgb thus illustrates how constraint and innovation combine to shape the long-term fate of a protein.
Genomic and transcriptomic analyses reveal the adaptation to semi-aquatic and aquatic life in spiders.
Fan Z, Wang LY, Luo B … +17 more , Ren TY, Gao JX, Liu P, Cheng LX, Cai YJ, Tan B, Huang Q, Deng MQ, Zuo Q, Zhang XY, Lu JZ, Sun LN, Irfan M, Liu N, Tong C, Bai M, Zhang ZS
Mol Biol Evol · 2026 Jun · PMID 42276590 · Full text
Spiders are largely terrestrial, but some lineages have independently adapted to marine and freshwater habitats. Although physiological and behavioral traits supporting these evolutionary transitions have been characteri...
Spiders are largely terrestrial, but some lineages have independently adapted to marine and freshwater habitats. Although physiological and behavioral traits supporting these evolutionary transitions have been characterized, the genomic basis of adaptation to aquatic and semi-aquatic habitats in spiders remains unclear. Here, we report a chromosome-level genome assembly for the aquatic spider Argyroneta aquatica. Comparative analysis of 22 spider species supports 2 independent transitions in semi-aquatic (∼56 Mya) and aquatic (∼44 Mya) lineages. The aquatic spider shows distinct respiratory morphology compared with terrestrial spiders, including anterior spiracles and denser tracheoles. Molecular evolution analyses identified lineage-specific shifts in selective constraint or evidence of positive selection linked to trachea development (eg Wnt-1, Catenin beta, TMEM234, Arp3), hypoxia response (eg Uqcrfs1, COX5B, SLC2A3), lipid metabolism (eg Pnliprp2, ND-ACP), and osmoregulation. In the semi-aquatic spiders (Desis spp.), we detected strengthened purifying selection or positive selection on genes involved in respiratory/energy metabolism (eg SdhD, SLC2A3) and ion transporters (eg. Slc24a5). Comparative results further indicate that the A. aquatica genome may harbor bacterial-origin genes homologous to ABC transporters (39 genes) and acyl-CoA dehydrogenases (ACADs; 21 genes), which may support metabolic or transport functions in the aquatic lineage. Transcriptomic and metabolomic profiling of A. aquatica under hypoxic challenge revealed metabolic reprogramming, including shifts in glycolytic and TCA intermediates and upregulation of genes that promote fatty-acid β-oxidation (eg Slc13a5, AACS), consistent with extended anoxia tolerance (>48 h). Overall, this work provides genomic resources and highlights genomic signatures associated with semi-aquatic and aquatic adaptation in spiders.
Bayesian Credible Sets for Phylogenetic Tree Topologies with Applications to Coverage Analysis and Cross-Model Comparison.
Klawitter J, Drummond AJ
Mol Biol Evol · 2026 Jun · PMID 42275602 · Full text
Credible intervals and credible sets, such as highest posterior density (HPD) intervals, form an integral statistical tool in Bayesian phylogenetics, both for phylogenetic analyses and for development. Readily available...
Credible intervals and credible sets, such as highest posterior density (HPD) intervals, form an integral statistical tool in Bayesian phylogenetics, both for phylogenetic analyses and for development. Readily available for continuous parameters such as base frequencies and clock rates, the vast and complex space of tree topologies poses significant challenges for defining analogous credible sets. Traditional frequency-based approaches are inadequate for diffuse posteriors where sampled trees are often unique. To address this, we introduce novel and efficient methods for estimating the credible level of individual tree topologies using tractable tree distributions, specifically Conditional Clade Distribution (CCD). Furthermore, we propose a new concept called α credible CCD, which encapsulates a CCD whose trees collectively make up α probability. We present algorithms to compute these credible CCDs efficiently and to determine credible levels of tree topologies as well as of subtrees. We evaluate the accuracy of these credible set methods leveraging simulated and real datasets. Furthermore, to demonstrate the utility of our methods, we use well-calibrated simulation studies to evaluate the performance of different CCD models. In particular, we show how the credible set methods can be used to conduct rank-uniformity validation and produce Empirical Cumulative Distribution Function (ECDF) plots, supplementing standard coverage analyses for continuous parameters.
Horizontal transfers of polydnavirus segments extend the known range of parasitoid attacks to stick insects and orthopterans.
Matrougui I, Oukkal S, Musset K … +4 more , Orieux E, Drezen JM, Charlat S, Gilbert C
Mol Biol Evol · 2026 Jun · PMID 42275600 · Full text
Horizontal gene transfer occurs beyond anecdotal frequencies in metazoans. Among insects, some parasitoid wasps even carry gene delivery agents called polydnaviruses (PDVs). These domesticated viral elements mediate the...
Horizontal gene transfer occurs beyond anecdotal frequencies in metazoans. Among insects, some parasitoid wasps even carry gene delivery agents called polydnaviruses (PDVs). These domesticated viral elements mediate the integration of wasp genes into the genome of parasitized hosts, thereby protecting developing larvae from immune defenses. The frequency of PDV-mediated transfers is sufficiently high that it could be exploited to better characterize the range of organisms attacked by parasitoid wasps. Here, we apply this rationale by screening for the specific molecular footprints of these transfers in 6,814 protostome genomes. We found a total of 6,556 PDV-mediated integrations, all of which were in insects. The distribution of these integrations is highly consistent with the known host range of PDV-encoding parasitoid wasps. Most were found in lepidopterans (6,260 integrations in 303 species)-the main hosts of PDV-encoding wasps-and a few were retrieved in sawflies (139 integrations in 14 species) and leaf beetles (four integrations in two species), also known to be parasitized by some of these wasps. Remarkably, we found a total of 232 integrations in three species of stick insects and one integration in an orthopteran, two insect lineages that have never been reported to be attacked by PDV-encoding wasps. We show that these integrations are mostly recent and that stick insects and sawflies were attacked recurrently by multiple wasp lineages. Overall, our study warrants accounting for stick insects and orthopterans as possible new targets of parasitoid attacks, both in community ecology and in assessments of biological control strategies.
Adaptive evolution of endothelial nitric oxide synthase (NOS3) may reduce cetacean susceptibility to decompression sickness.
Tian R, Zhao L, Li T … +3 more , Yan Y, Seim I, Yang G
Mol Biol Evol · 2026 Jun · PMID 42275597 · Full text
Cetaceans tolerate repeated diving bouts. While the extent to which cetaceans experience decompression sickness remains debated, this group of fully aquatic mammals must have evolved a tolerance to damaging nitrogen (N2)...
Cetaceans tolerate repeated diving bouts. While the extent to which cetaceans experience decompression sickness remains debated, this group of fully aquatic mammals must have evolved a tolerance to damaging nitrogen (N2) gas bubbles that can form during overly rapid ascents or after prolonged dives. Here, we present the first in-depth molecular evolutionary analysis of the nitric oxide synthase gene family across cetaceans and identify cetacean-specific amino acid substitutions in NOS3 (encoding endothelial nitric oxide synthase) that likely arose in a stem cetacean ancestor, coincident with the transition to obligate aquatic life. Using in vitro assays, we demonstrate that cetacean endothelial nitric oxide synthase exhibits enhanced enzymatic activity and function, potentially mediated by strengthened binding to its molecular chaperone Hsp90. Our findings provide a molecular foundation for an evolved, more resilient vascular system in cetaceans, offering new insights into their adaptations to a hyperbaric environment.
Gene loss and compensatory evolution as a source of metabolic preadaptations.
Kalapis D, Kovács K, Balogh D … +6 more , Maharramov E, Ajibola W, Silander OK, Fehér T, Pál C, Papp B
Mol Biol Evol · 2026 Jun · PMID 42275596 · Full text
Gene loss is common, yet whether it is merely an evolutionary dead-end or can promote future adaptation to new environments remains debated. Here, we systematically tested whether harmful loss of metabolic genes, followe...
Gene loss is common, yet whether it is merely an evolutionary dead-end or can promote future adaptation to new environments remains debated. Here, we systematically tested whether harmful loss of metabolic genes, followed by compensatory evolution, generates preadaptations to alternative nutrients in Escherichia coli. Our analysis revealed a striking outcome beyond simple growth restoration, where repair of a genetic defect yielded growth exceeding the unperturbed wild type on carbon sources not encountered during evolution. Such latent growth gains occurred across multiple deletion backgrounds and carbon sources, with growth rate increases up to 46% relative to the wild type. In some cases, the corresponding ancestral deletion strain failed to grow on these carbon sources, indicating functional innovations relative to the deletion ancestor. Genetic reconstruction and transcriptomic profiling implicate regulatory reprogramming, particularly in carbon catabolite repression and nutrient uptake, as mechanisms underlying latent growth gains. In conclusion, evolutionary recovery from gene loss can rapidly produce preadaptations to future environments in the absence of direct selection.
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