Molecular Biology And Evolution[JOURNAL]
Sun
200 papers
Mutation rate estimate and population genomic analysis reveals decline of koalas prior to human arrival.
Kovacs TGL, Foley NM, Silver LW … +4 more , McLennan EA, Murphy WJ, Hogg CJ, Ho SYW
Mol Biol Evol · 2026 Jun · PMID 42262248 · Full text
The koala (Phascolarctos cinereus), an iconic Australian marsupial, has experienced substantial historical and contemporary population declines. Identifying the drivers of these declines has been hindered by limited geno...
The koala (Phascolarctos cinereus), an iconic Australian marsupial, has experienced substantial historical and contemporary population declines. Identifying the drivers of these declines has been hindered by limited genomic data and uncertainty regarding the koala mutation rate. Here, we report a direct estimate of the koala mutation rate, based on genome sequences of four parent-offspring trios, yielding a mean of 6.12 × 10-9 mutations per base pair per generation (95% confidence interval: 5.03 to 7.45 × 10-9). Using this estimate of the mutation rate, we reconstructed the demographic history of koalas using 457 whole-genome sequences sampled across their entire range. Our results refine the estimated timing of past changes in population size, suggesting a large decline beginning ∼100 kya, before the arrival of humans in Australia. The koala population then split into five genetic populations 6 to 30 kya, which are now distributed along the east coast of Australia. We also use our estimate of the mutation rate to infer recombination maps for each koala population, confirming lower recombination rates in marsupials than in eutherian mammals. Using these estimates of population-specific recombination rates, we inferred the timing of recent population declines for koalas across all eastern states. These findings provide critical insights into the evolutionary history of koalas, while highlighting the impacts of using species-specific estimates of evolutionary rates on the inference of demographic histories. Our estimates of the genome-wide mutation rate and population-specific recombination maps for koalas provide valuable resources for future evolutionary and conservation analyses of marsupials.
Limited selection on Neanderthal DNA in 30,780 recently admixed genomes with African-like ancestry.
Pfennig A, Lachance J
Mol Biol Evol · 2026 Jun · PMID 42252278 · Full text
Following introgression, Neanderthal DNA was initially purged from non-African genomes, but the evolutionary fate of remaining introgressed DNA in recently admixed genomes with African-like genetic ancestry has not been...
Following introgression, Neanderthal DNA was initially purged from non-African genomes, but the evolutionary fate of remaining introgressed DNA in recently admixed genomes with African-like genetic ancestry has not been tested at biobank-scale. In these admixed genomes, Neanderthal alleles encountered a novel genetic background, potentially leading to renewed selective pressures. We analyzed 30,780 admixed genomes from the All of Us research program, in which Neanderthal alleles were introduced into an African-like genetic background during the last 15 generations. Observed amounts of Neanderthal DNA approximately match expectations based on ancestry proportions, suggesting neutral evolution. In line with this, simulations under a realistic demographic scenario suggest that strong genome-wide selection of Neanderthal DNA (s ≥ |0.1|) would have led to significant changes in recent ancestry proportions that are not observed in real data. Nevertheless, we identified genomic regions that have significantly less or more Neanderthal ancestry than expected and are associated with spermatogenesis, cell cycle regulation, and neuronal signaling, among other biological processes. We also identified four novel introgression desert-like regions in recently admixed genomes, whose genetic features are compatible with hybrid incompatibilities and intrinsic negative selection. Overall, we find that much of the remaining Neanderthal DNA in human genomes is likely not under strong selection, and complex evolutionary dynamics have shaped introgression landscapes in our species.
Multiple Origins of a Sex Ratio Supergene in Formica Ants.
Lagunas-Robles G, Purcell J, Shimota E … +1 more , Brelsford A
Mol Biol Evol · 2026 Jun · PMID 42241639 · Full text
Polymorphisms in complex traits often map to regions of the genome with two or more functional mutations with little or no recombination between them. These "supergenes" are usually found in a single species or a few clo...
Polymorphisms in complex traits often map to regions of the genome with two or more functional mutations with little or no recombination between them. These "supergenes" are usually found in a single species or a few closely related species. However, when supergenes persist through a large number of speciation events, they may take on additional functions in different lineages. Here, we investigate how an ancient supergene has evolved to gain novel function. In Formica ants, most species have a "social" supergene with M and P haplotypes that determine whether a colony is headed by a single queen or multiple queens, respectively, and which diverged from each other at least 20 million years ago. At least three Formica species have an additional haplotype on the same chromosome, termed MD, associated with female-biased offspring sex ratio at the colony level. Do the MD haplotypes share a common origin or did they evolve convergently? With whole-genome resequencing, we identify MD haplotypes in three additional species and use variation across six Formica species to examine the evolutionary history of the MD haplotype. We identify two putative origins of the MD haplotype, one in the ancestor of five Nearctic species, and a second in the Palearctic species, Formica cinerea. We present evidence that the MD haplotypes originated from recombination between M and P haplotypes. The discovery of two MD haplotypes convergently evolving from distinct recombination events between two ancestral supergene haplotypes illustrates how supergenes can diversify and gain additional phenotypes.
Enhancement of hidden Markov model analyses for improved inference of archaic introgression in modern humans.
Coll Macià M, Skov L, Bæk ZED … +1 more , Hobolth A
Mol Biol Evol · 2026 Jun · PMID 42231692 · Full text
Insights into the admixture history between modern and archaic humans require accurately inferred introgressed fragments within modern genomes. Here, we introduce two enhancements to hidden Markov models (HMMs) implement...
Insights into the admixture history between modern and archaic humans require accurately inferred introgressed fragments within modern genomes. Here, we introduce two enhancements to hidden Markov models (HMMs) implemented in hmmix. First, we develop a method for sampling hidden state sequences conditional on observed genomic data, enabling robust estimation of admixture summary statistics-such as admixture proportion and fragment length distributions. This represents an improvement compared to relying solely on point estimates as provided by classical decoding methods. Additionally, we integrate the Finite Markov Chain Imbedding (FMCI) framework, allowing exact analytical calculation of these admixture statistics, tailored to large scale human genomes. Second, we implement a novel hybrid decoding method which combines the strengths of Viterbi and Posterior decoding methods, substantially improving the reliability of archaic fragments identified. We validate these improvements on data from the 1000 Genomes Project and demonstrate that our sampling method yields more accurate admixture estimates from single individuals compared to existing approaches requiring extensive population-level datasets. Moreover, we show how hybrid decoding can be instrumental in resolving the inference of local archaic haplotype structure in modern human genomes. These methodological advancements will enhance HMM-based analyses in any field of science and will provide deeper insight into the complex history of genetic interactions between archaic and modern human populations.
On the dynamic caddisfly silk H-fibroin gene: a population study in a net-spinning species.
Stewart RJ, Powell A, Heckenhauer J … +6 more , Pauls SU, Jijon G, Standring S, Hayashi CY, Baker RH, Frandsen PB
Mol Biol Evol · 2026 Jun · PMID 42231630 · Full text
Larvae of the caddisfly Arctopsyche grandis BANKS build protective structures and spin silken capture nets in flowing water. Caddisfly H-fibroin, the major protein component of its silk fibers, has a blocky structure wit...
Larvae of the caddisfly Arctopsyche grandis BANKS build protective structures and spin silken capture nets in flowing water. Caddisfly H-fibroin, the major protein component of its silk fibers, has a blocky structure with repeating units defined as beginning with a [(SX)nE]m region followed by a G-rich spacer. Previous observation of H-fibroin allelic variation in haploid-resolved individuals led us to investigate allelic variation within two geographically close but separated natural populations of A. grandis. The genomes of 18 individuals were sequenced, and 34 haploid-resolved H-fibroin sequences were extracted. Twenty-four unique alleles were identified in 18 genomes, revealing the dynamic nature of the H-fibroin gene. H-fibroin length variations of at up to 25% were tolerated. The major source of the length variations were large-scale deletions and insertions of entire [(SX)nE]m blocks. Small scale indel events were numerous, nonrandomly distributed, and constrained to a few types. One, a 44 residue indel comprising two (SX)nE motifs changed m ± 2 by splitting direct tandem repeats without disrupting tertiary structure or block boundaries. The G-rich spacers are of two types, the first distinguished by repeating GLGPH pentapeptides. Indels within this spacer type occur as multiples of the GLGPH pentapeptide. The other category of G-rich spacer was confined to a narrow length distribution. Overall, the results demonstrate the rapid evolution of the caddisfly H-fibroin gene and the wide range of H-fibroin structural polymorphism tolerated in functional capture net silk. At the same time, the limited nature of the indels point to the critical structural features of H-fibroin.
The Phylodynamic Threshold of Measurably Evolving Populations.
Weber A, Kende J, Duitama González C … +2 more , Översti S, Duchene S
Mol Biol Evol · 2026 Jun · PMID 42229890 · Full text
The molecular clock is a fundamental tool for understanding the time and pace of evolution, requiring calibration information alongside molecular data. Sampling times are often used for calibration since some organisms a...
The molecular clock is a fundamental tool for understanding the time and pace of evolution, requiring calibration information alongside molecular data. Sampling times are often used for calibration since some organisms accumulate enough mutations over the course of their sampling period. This practice ties together two key concepts: measurably evolving populations and the phylodynamic threshold. Our current understanding suggests that populations meeting these criteria are suitable for molecular clock calibration via sampling times. However, the definitions and implications of these concepts remain unclear. Using Hepatitis B virus-like simulations and analyses of empirical data, this study shows that determining whether a population is measurably evolving or has reached the phylodynamic threshold does not only depend on the data, but also on model assumptions and sampling strategies. In Bayesian applications, a lack of temporal signal due to a narrow sampling window results in a prior that is overly informative relative to the data, such that a prior that is potentially misleading typically requires a wider sampling window than one that is reasonable. In our analyses we demonstrate that assessing prior sensitivity is more important than the outcome of tests of temporal signal. Our results offer guidelines to improve molecular clock inferences and highlight limitations in molecular sequence sampling procedures.
Molecular assessment of recombination processing across genetically diverse mouse strains reveals sexually dimorphic determinants of crossover distribution beyond chromosome length.
Horan TS, Wood A, Tanis S … +2 more , Peirau-Gabarrell C, Cohen PE
Mol Biol Evol · 2026 Jun · PMID 42226637 · Full text
Meiotic recombination generates crossovers (COs), reciprocal exchanges between homologous chromosomes critical for accurate chromosome segregation. Inappropriate CO frequency and distribution drive aneuploidy in human oo...
Meiotic recombination generates crossovers (COs), reciprocal exchanges between homologous chromosomes critical for accurate chromosome segregation. Inappropriate CO frequency and distribution drive aneuploidy in human oocytes, with error rates up to 10-fold higher than in sperm despite females exhibiting higher CO frequencies. COs form in the context of the proteinaceous synaptonemal complex (SC) that tethers homologs during prophase I. SC length strongly correlates with CO number, and sexual dimorphism in recombination has long been attributed to longer SCs in females. However, this model is challenged by wild-derived PWD mice in which males consistently generate more COs despite having shorter SCs. Here, we exploit natural genetic variation among inbred mouse strains to dissect the structural and regulatory basis of sexually dimorphic CO regulation. Using cytological markers of SC assembly (SYCP3), recombination progression (RAD51, MSH4), class I CO designation (HEI10, MLH1/MLH3), and chiasmata, we show that SC length is not the sole predictor of CO number. PWD males exhibit stronger CO interference and higher CO number than females, despite reduced SC length. Notably, females show reduced efficiency in designating recombination intermediates to become COs, whereas PWD males display exceptional proficiency. Unexpectedly, although class II COs are rare, they play a disproportionate role in ensuring that every chromosome pair receives at least one CO, thereby safeguarding against aneuploidy. Together, these findings challenge the prevailing view that SC length is the primary determinant of sexually dimorphic CO rates and instead highlight sex-specific regulation of CO designation and pathway usage as key drivers of recombination outcomes.
Functional conservation with mechanistic drift: AMP activation in the evolution of archaeal sugar kinases.
M Herrera S, Vallejos-Baccelliere G, Malavé D … +3 more , Hernández-Cabello L, Castro-Fernandez V, Guixé V
Mol Biol Evol · 2026 Jun · PMID 42216562 · Full text
Although allosteric regulation has been pointed out as one of the cornerstones of biological function, it has been a scarcely studied phenomenon in Archaea carbohydrate metabolism. Given its central role in metabolism, w...
Although allosteric regulation has been pointed out as one of the cornerstones of biological function, it has been a scarcely studied phenomenon in Archaea carbohydrate metabolism. Given its central role in metabolism, we experimentally investigated how allosteric regulation and its underlying kinetic mechanism evolved along evolutionary pathways within the archaeal ADP-dependent kinase family. Using ancestral sequence reconstruction, we resurrected key ancestors of this family and show that AMP regulation is an ancestral feature retained exclusively in lineages encoding bifunctional ADP-dependent phosphofructokinase (PFK)/glucokinase (GK) enzymes, which are restricted to methanogenic organisms, whereas it is lost in lineage-specific PFK enzymes. Notably, although AMP-dependent allosteric regulation is conserved among bifunctional ADP-PFK/GK enzymes, the kinetic mechanisms underlying activation are not. Instead, we observed a diversity of activation mechanisms (increased affinity for substrates, enhanced catalytic efficiency, or a combination of both), distributed along a 2-billion-year evolutionary trajectory, and that persists across different temperatures studied, both in extant and ancestral enzymes. These results highlight that the structural scaffold of this protein family is evolutionarily robust, preserving function while allowing substantial diversification of the underlying activation mechanisms under sequence variation. Based on these findings, we propose the concept of mechanistic drift, in which evolutionary pressures primarily act on adaptive functional traits that confer an adaptive advantage, rather than on the specific molecular mechanisms by which they are achieved. This framework has broad implications for macromolecular evolution, illustrating how long-term functional conservation can coexist with extensive physicochemical mechanistic diversity.
Intrahost mutational dynamics parallel long-term genome evolution in endosymbionts.
Kwak Y, Bennett G
Mol Biol Evol · 2026 May · PMID 42212590 · Publisher ↗
Obligate endosymbionts of insects undergo extreme genome evolution, marked by accelerated molecular evolution, severe base-pair compositional bias, and massive gene loss. However, the microevolutionary processes driving...
Obligate endosymbionts of insects undergo extreme genome evolution, marked by accelerated molecular evolution, severe base-pair compositional bias, and massive gene loss. However, the microevolutionary processes driving these patterns remain poorly understood, as they occur at intrahost population scales that are rarely captured. To address this gap, we measured intrahost genetic diversity of two endosymbionts, Karelsulcia and Nasuia, from the aster leafhopper, Macrosteles quadrilineatus (Hemiptera: Cicadellidae). Contrary to the theoretical expectation of strict clonality, we found that both endosymbionts harbor measurable intrahost genetic variation, with lineage-specific mutational dynamics that parallels long-term evolutionary trends. Karelsulcia showed sparse intrahost variation dominated by repeat-associated indels, while Nasuia exhibited more abundant single-nucleotide mutations that appear to shape genome-wide A + T bias. Mitochondrial heteroplasmy did not covary with endosymbiont nucleotide diversity, indicating that these patterns are not driven by host-level dynamics. Notably, recurrent nonsynonymous variants in Nasuia affect essential genes for amino acid biosynthesis and translation. The intrahost mutational patterns we observed in endosymbionts are consistent with long-term sequence changes between our population founder genome and contemporary endosymbiont populations after ∼11 years of maintenance. Taken together, our results demonstrate how distinct mutational processes operating at the intrahost populations scale drive macroevolutionary patterns in endosymbiont genomes. Moreover, our study establishes that laboratory endosymbiont systems provide a powerful framework for dissecting and understanding these fundamental evolutionary processes.
Single-cell analyses of tissue regeneration in two true jellyfish.
Li Y, Law STS, Nong W … +18 more , So WL, Xie Y, Leung TCN, Li TH, Tse J, Yip HY, Jin O, Zhang J, Chui APY, Lau KF, John A, Kai ZP, Bendena WG, Hayward A, Wei Y, Chan TF, Ngai SM, Hui JHL
Mol Biol Evol · 2026 Jun · PMID 42212572 · Full text
The phylum Cnidaria is the outgroup of Bilateria and includes sea anemones, corals, hydroids, and jellyfish. Cnidarians play crucial ecological roles in marine ecosystems, including the formation of highly diverse and pr...
The phylum Cnidaria is the outgroup of Bilateria and includes sea anemones, corals, hydroids, and jellyfish. Cnidarians play crucial ecological roles in marine ecosystems, including the formation of highly diverse and productive coral reefs, and acting as important predator and prey species. They are also well known for their remarkable regeneration capacities. Here, we report single-cell RNA sequencing of bell tissue remodeling/regeneration after amputation in two species of scyphozoans or "true jellyfish," the Asian moon jelly, Aurelia coerulea, and the flame jellyfish, Rhopilema esculentum. We delineated 12 cell populations in Aurelia and Rhopilema and revealed their respective marker genes and enriched gene pathways. During this process, conserved transcription factor Otx, TFAP2A, Erg, NFIA, and Wnt/β-catenin signaling pathway genes were identified. Additionally, we discovered two conserved, sequentially activated patterns, with putative proliferative cells, gastrodermal cells, neural cells, and secretory gland cells modulated in the first phase, followed by cnidocytes in the second phase. Further comparison among cnidarian genomes identified a suite of lineage-specific scyphozoan genes, a subset of which were frequently significantly expressed in cnidocytes in both jellyfish species. Using powerful single-cell RNA sequencing approaches, this study elucidates the evolution of lineage-specific genetic networks and biological processes in true jellyfish, which remain comparatively poorly studied, and in particular provides key insights into the molecular pathways underlying their remarkable regenerative capacity.
Ancient but dynamic: structural expansion, massive gene duplication, and transposable element colonization in a supergene controlling ant social organization.
Boulain H, Deshmukh R, Avril A … +6 more , Blacher P, Bourquin M, Yek SH, Zahnd S, Tran Van P, Chapuisat M
Mol Biol Evol · 2026 Jun · PMID 42192201 · Full text
Supergenes are clusters of linked loci that underlie complex alternative phenotypes, such as colony social organization in ants. In many species of the genus Formica, a 30 million-year-old supergene determines whether co...
Supergenes are clusters of linked loci that underlie complex alternative phenotypes, such as colony social organization in ants. In many species of the genus Formica, a 30 million-year-old supergene determines whether colonies have one queen (monogyny) or multiple queens (polygyny), yet the detailed architecture of this genetic polymorphism remains poorly known. Here, we investigate the structural and functional evolution of the supergene haplotypes controlling alternative social forms in Formica selysi. The comparison of chromosomal-level genome assemblies for each social form reveals a 13.8-Mbp long rearranged supergene comprising three large inversions and a transposition, resulting in reduced recombination and high differentiation between haplotypes. The rearranged, derived polygynous haplotype has accumulated transposable elements (TEs) and gene duplicates. It also exhibits haplotype-specific gene expression and gene specialization. Notably, the Formica genus shows a large expansion of the Ubiquitin Conjugation Factor E4 B gene family, which is significantly enriched in the supergene. Despite its ancient origin, the supergene shows sparse signs of degeneration and little accumulation of deleterious variations. Overall, our results demonstrate that the supergene haplotype associated with multi-queen colonies has undergone enrichment of lineage-specialized single- and multi-copy genes with haplotype-specific expression patterns that likely contribute to the phenotype. A combination of relaxed and purifying selection allowed gene duplicates and TEs to accumulate, but prevented the accumulation of deleterious mutations, which helps to explain the long-term persistence of this large social supergene.
Retrotransposed gene copies persist under relaxed selection in wild Spodoptera frugiperda.
Nam K, Gimenez S, An H … +8 more , Durand K, Gasser M, Yainna S, Legeai F, Beuzelin J, Heckel DG, Hänniger S, d'Alençon E
Mol Biol Evol · 2026 Jun · PMID 42192156 · Full text
Copy number variations (CNVs) are major sources of genetic variation, affecting large portions of genomes. Typical CNVs are known to have short evolutionary half-lives due to deleterious effects, with documented events o...
Copy number variations (CNVs) are major sources of genetic variation, affecting large portions of genomes. Typical CNVs are known to have short evolutionary half-lives due to deleterious effects, with documented events of adaptive evolution. However, it is not known whether the same trends apply to CNVs preserving intact Open Reading Frames (iORF-CNVs), which can encode functional proteins. Here, we investigate the mechanistic origins and evolutionary dynamics of iORF-CNVs in Spodoptera frugiperda, a globally distributed pest species where CNV-mediated adaptive evolution has been reported. Using PacBio HiFi reads, we generated high-quality, individually assembled genomes for 36 field-collected individuals and identified 349 genes with polymorphic iORF-CNVs. These elements are short, intronless, and display molecular signatures of LINE-mediated retrotransposition, including cis- and trans-acting effects. A majority of iORF-CNVs (68.0% to 77.28%) exhibited at least one molecular signature of retrotransposition. iORF-CNVs showed lower divergence at the first and second codon positions than at the third codon positions, but they had higher nonsynonymous-to-synonymous polymorphism ratios than non-iORF-CNV genes, implying purifying selection with relaxed constraint. Orthology analyses indicated that these CNVs originate from genes under weak evolutionary constraint, while transcriptomic and promoter motif analyses revealed that many are transcribed and retain regulatory features. We conclude that observed iORF-CNVs are generated through retrotransposition from weakly constrained genes and that the duplicates are selectively maintained for coding potential, albeit under reduced purifying selection compared with non-iORF-CNV genes. These results imply that pseudogenization is not an inevitable evolutionary fate of retrotransposed gene copies when the open reading frame is preserved.
Compensatory evolution facilitates loss of prfB autoregulation in Pseudomonas fluorescens SBW25.
Lim S, Bertels F, Lopez-Garrido J … +1 more , Gallie J
Mol Biol Evol · 2026 Jun · PMID 42186845 · Full text
Understanding why some traits are maintained whereas others are repeatedly lost is a central question in evolutionary biology. Here, we address this question through the evolutionary dynamics of autoregulation of prfB, w...
Understanding why some traits are maintained whereas others are repeatedly lost is a central question in evolutionary biology. Here, we address this question through the evolutionary dynamics of autoregulation of prfB, which encodes peptide-chain release factor 2 (RF2), a factor in bacterial translation termination. RF2 recognizes UGA and UAA stop codons and catalyzes polypeptide release. In many species, prfB contains an internal UGA stop codon that causes premature termination by RF2. Full RF2 synthesis depends on a + 1 programed ribosomal frameshifting (PRF) event at this stop codon, which occurs more frequently when RF2 levels are low, resulting in autoregulation of prfB expression. While widespread, this mechanism has been lost repeatedly across bacteria. We combined phylogenetics, experimental evolution, and molecular genetics to investigate the evolutionary forces underlying this loss. Phylogenetically informed analyses revealed no significant correlation between autoregulation and UGA stop codon usage, and autoregulation elimination in Pseudomonas fluorescens SBW25 had no detectable fitness effect. However, engineered mutations that reduced frameshifting at the prfB autoregulatory site caused fitness defects that were compensated by two classes of mutation: mutations affecting ribosome-associated proteins (RsmA, RsmH, RplI), and single-nucleotide deletions in prfB that adjusted the reading frame to bypass the internal stop codon, eliminating autoregulation. These results suggest that loss of prfB autoregulation can be facilitated by compensatory mutations when frameshifting at the prfB autoregulatory site is compromised and RF2 production is insufficient. Our findings illustrate how compensatory evolution can favor trait loss when the fitness benefit of losing the trait outweighs its cost.
Phylogenomic analysis of vocal fold length evolution reveals links between vocal and auditory systems in terrestrial mammals.
Zhou X, Liu F, Liu M … +10 more , Hu Z, Zhang L, Wang X, Zhou Z, Shu Y, Sun W, Bi S, Jin L, Lin Z, Zhang M
Mol Biol Evol · 2026 May · PMID 42184971 · Publisher ↗
Vocal fold length is a primary anatomical determinant of pitch and fundamental frequency in terrestrial mammal vocalizations, playing a key role in social communication, mate attraction, and competition. However, its phe...
Vocal fold length is a primary anatomical determinant of pitch and fundamental frequency in terrestrial mammal vocalizations, playing a key role in social communication, mate attraction, and competition. However, its phenotypic diversification and genetic basis remain unclear. Here, using a phylogenetic genotype-to-phenotype mapping (PhyloG2P) framework to 75 species representing Primates, Carnivora, and Artiodactyla, we investigate the evolutionary dynamics and genetic architecture of relative vocal fold length (RVFL), accounting for allometric trends. Phylogenetic comparative analyses reveal similar patterns of RVFL variation among orders and strong adaptive responses supporting the acoustic size exaggeration hypothesis. Correlation analyses further reveal the potential driving role of social organization in RVFL evolution. Comparative genomics identifies 25 hearing-related genes showing rapid evolution, positive selection, lineage-specific mutations and coevolution with RVFL, suggesting a reciprocal evolutionary interplay between vocal and auditory systems. This genetic link is supported by laryngeal MRI evidence from wild-type and Pjvk knockout mice, where PJVK is identified as a candidate gene through our PhyloG2P analyses. Additionally, pathways related to peptide hormone secretion and neural regulation appear to mediate RVFL variation. Together, these findings advance our understanding of the genetic and evolutionary mechanisms driving vocal fold diversity in terrestrial mammals and highlight the links between vocal and auditory systems, offering new insights into the origins of vocal communication.
Quantifying the Influence of Genetic Context on Duplicated Mammalian Genes.
Moffett AS, Falcón-Cortés A, Di Pierro M
Mol Biol Evol · 2026 Jun · PMID 42172680 · Full text
Gene duplication is a fundamental part of evolutionary innovation. While paralogs frequently exhibit asymmetric evolutionary rates, the extent to which genetic context influences asymmetric evolution remains unclear. In...
Gene duplication is a fundamental part of evolutionary innovation. While paralogs frequently exhibit asymmetric evolutionary rates, the extent to which genetic context influences asymmetric evolution remains unclear. In this study, we investigate the role of genetic context in shaping evolutionary divergence within both single-gene and multigene duplications, leveraging microsynteny to differentiate source and target copies. Using a dataset of 193 mammalian genome assemblies and a bird outgroup, we systematically analyze patterns of sequence divergence between paralogs. We find that most paralogs have no detectable difference in their evolutionary rates. When there is rate asymmetry, target copies, those relocated to new genomic locations, exhibit elevated evolutionary rates compared to source copies in ancestral locations. This asymmetry is influenced by the genomic distance between copies, the size of the duplicated region, and the position within multigene duplications. We also demonstrate that the "choice" of the fast-evolving copy in multigene duplications occurs in a collective, block-wise manner more often than expected by random chance. Our findings highlight the importance of genetic context in modulating postduplication divergence, where differences in cis-regulatory elements and co-expressed gene clusters between source and target copies may be responsible. This study presents a large-scale study of asymmetric evolution in duplications of varying size, offering new insight into how genome architecture shapes functional diversification of paralogs.
Evidence for an early cadherin-catenin interaction network in ctenophores.
Guttieres LJ, Singh A, Senatore A … +1 more , Martindale MQ
Mol Biol Evol · 2026 Jun · PMID 42172677 · Full text
The cadherin-catenin complex (CCC) is a calcium-dependent assembly that is essential for the organization and function of animal cells and tissues. CCC components form adherens junctions that link cell adhesion to the ac...
The cadherin-catenin complex (CCC) is a calcium-dependent assembly that is essential for the organization and function of animal cells and tissues. CCC components form adherens junctions that link cell adhesion to the actin cytoskeleton and important signaling pathways that control processes, such as gene expression, cell polarity, and growth. While the CCC has been extensively studied and known to be conserved across most metazoan lineages, its occurrence in ctenophores, one of the earliest branching groups, has been questioned, with implications for the origins of multicellularity in animals. Here, we show that the ctenophore Mnemiopsis leidyi possesses a reduced cadherin repertoire yet retains conserved interactions characteristic of the CCC. Phylogenetic analyses identified a novel ctenophore-specific cadherin phylogenetically distant from major cadherin families from other animals. Screening a custom yeast two-hybrid library, derived from M. leidyi embryo cDNA, with the cytoplasmic tail of this noncanonical cadherin-like protein identified known CCC components β-catenin, p120, and Hakai as interacting proteins. Similarly, a screen using M. leidyi α-catenin as bait identified β-catenin, vinculin, and other known actin cytoskeleton-associated proteins. Directed yeast two-hybrid assays confirmed key interactions and demonstrated that targeted mutagenesis of conserved residues abolished binding, as is observed in other metazoans. Together, these findings suggest that core molecular interactions underlying the CCC are conserved in M. leidyi, consistent with the hypothesis that a functional CCC was an ancestral trait foundational to the evolution of multicellular animals.
The evolution of gene functional repertoire in Amorphea: divergent strategies across Amoebozoa, Fungi, and Metazoa.
Gàlvez-Morante A, Berney C, Richter DJ
Mol Biol Evol · 2026 May · PMID 42165094 · Full text
Metazoa and Fungi have been extensively studied to reconstruct the trajectory of Opisthokont evolution. Their sister group, Amoebozoa, provides additional potential to generate valuable insights into the origins of Opist...
Metazoa and Fungi have been extensively studied to reconstruct the trajectory of Opisthokont evolution. Their sister group, Amoebozoa, provides additional potential to generate valuable insights into the origins of Opisthokont lineages. Amoebozoa represent a diverse group of amoeboid organisms, which have adapted to a wide range of environments and ecological niches. Studying Amoebozoa not only helps to illuminate Opisthokont evolution but also reveals the mechanisms that have driven amoebozoan ecological success. Here, we report the discovery of Apostamoeba explorator strain BEAP0066, representing a novel lineage within Amoebozoa with intriguing behaviors like the "double-amoeba," a behavior characterized by the bipolarization of a cell into two poles that coexist and act as two semi-independent cells. By analyzing the gene content of A. explorator and diverse amoebozoans with ancestral gene content reconstructions, correspondence analyses of Clusters of Orthologous Groups category composition and protein families database (Pfam) clan clustering, we revealed distinct evolutionary trajectories for Amoebozoa, Metazoa, and Fungi. Amoebozoa retained an ancestral Amorphea-like state, characterized by an enrichment of genes related to motility, phagocytosis, and rapid cellular response, while Metazoa specialized in multicellularity-related genes and Fungi in metabolism and transport. These findings suggest that retention of gene function composition, rather than gene loss, played a key role in shaping Amoebozoa evolution.
Epistasis and background dependence in the evolution of Omicron variants of the SARS-CoV-2 spike protein.
Moulana A, Dupic T, Desai MM
Mol Biol Evol · 2026 May · PMID 42142336 · Full text
The rapid and repeated emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, particularly within the Omicron lineage, highlights the virus's remarkable ability to adapt under shifting immune...
The rapid and repeated emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants, particularly within the Omicron lineage, highlights the virus's remarkable ability to adapt under shifting immune pressures. A central molecular battleground in this evolutionary arms race is the spike receptor-binding domain, which must simultaneously maintain high affinity for the human ACE2 receptor while evading recognition by neutralizing antibodies. In this study, we construct and analyze multiple combinatorial libraries of SARS-CoV-2 receptor-binding domain variants spanning major branches of Omicron evolution, including BA.1, BA.2, BA.5, XBB, and JN.1. Using high-throughput yeast display and binding assays, we map the effects of thousands of mutations and their combinations on ACE2 binding and antibody evasion. Our results reveal that while many receptor-binding domain mutations exhibit additive effects, several mutations interact epistatically in a background-dependent manner. In particular, we identify synergistic interactions between BA.1 and BA.5 mutations that enhance antibody evasion, likely facilitating the rise of recombinant variants and convergent evolution. Conversely, some mutations show lineage-restricted compatibility, suggesting potential constraints on future evolutionary trajectories. Our comprehensive genotype-to-phenotype maps uncover both rugged and smooth regions of the viral fitness landscape and underscore the importance of epistasis in shaping SARS-CoV-2 evolution. These findings improve our ability to anticipate future viral variants and provide a framework for understanding how host-pathogen coevolution unfolds at the molecular level.
New lineages provide insights into the convergent evolution of extreme salt adaptation within symbiotic Archaea.
Hamm JN, Dombrowski N, Valentin-Alvarado LE … +3 more , Greening C, Williams TA, Spang A
Mol Biol Evol · 2026 May · PMID 42139541 · Full text
Environmental genomics has led to the discovery of many new lineages of archaea, including "DPANN" (or Nanobdellati), comprising organisms with small genomes, reduced gene content, and potentially symbiotic or parasitic...
Environmental genomics has led to the discovery of many new lineages of archaea, including "DPANN" (or Nanobdellati), comprising organisms with small genomes, reduced gene content, and potentially symbiotic or parasitic lifestyles. DPANN live in various environments, and several lineages have been identified that are adapted to extremely high-salt concentrations, including the Nanohaloarchaeota. Since it was long thought that the Haloarchaea (within "Euryarchaeota") were the only high salt-adapted archaea, the origins of these genome-reduced halophiles have been debated. Here, we used phylogenetic, comparative genomic, and gene tree-species tree reconciliation approaches to resolve the evolution of halophily within DPANN, making use of recently published genomes that help to inform the phylogenetic placement and genome evolution of salt-adapted lineages. Phylogenetic analysis placed Nanohaloarchaeota sister to a previously uncharacterized lineage, which we here refer to as Terrarchaeota. Terrarchaeota appear to be predominantly anaerobic thermophiles that are not adapted to high-salt concentrations, indicating that adaptation to high salt evolved after their divergence from Nanohaloarchaeota. Furthermore, our analyses identified genomic hallmarks of salt adaptation in another recently discovered halophilic DPANN lineage within Aenigmatarchaeota, the Haloaenigmatarchaeaceae. We found that the Nanohaloarchaeota and Haloaenigmatarchaeaceae have distinct sets of proteins that enable life at high salt concentrations but share a common mechanism of evolutionary adaptation, in which niche-relevant genes were acquired horizontally from their halophilic hosts. This work provides the first detailed investigation into the enigmatic Terrarchaeota, and new insights into the convergent evolution of high salt adaptation within symbiotic clades of Archaea.
Genomic insights into the admixture history and adaptive evolution of the Zhuang people.
Mao C, Li S, Lu Y … +7 more , Liu Q, Deng L, Gao Y, Zhang X, Chen H, Yang Y, Xu S
Mol Biol Evol · 2026 May · PMID 42135529 · Full text
The Zhuang, China's largest ethnic minority with over 17 million individuals, represent a critical yet understudied population for understanding East Asian genetic diversity and population history. Here, we present the f...
The Zhuang, China's largest ethnic minority with over 17 million individuals, represent a critical yet understudied population for understanding East Asian genetic diversity and population history. Here, we present the first high-coverage whole-genome (>30×) and exome (>70×) sequencing study of the Zhuang (ZUN), integrating ancient and modern genomic data to reconstruct their evolutionary trajectory. We show that ZUN derive ∼68% of their ancestry from the Tai-Kadai-speaking people, diverging ∼3,000 to 5,000 years ago (ya), with the Maonan as their closest genetic relatives. Our analyses support a shared origin of Tai-Kadai and Austronesian populations ∼7,000 ya, predating their divergence from Sino-Tibetan groups ∼16,000 ya. Substantial gene flow from Han Chinese since ∼4,000 ya reduced genetic divergence between ZUN and northern East Asians to ∼12,000 years. The ZUN ancestral gene pool formed 5,000 to 3,000 ya through multiple admixture waves, with 87% contribution from southern populations and 12% from northern groups. Demographic modeling indicates continuous population expansion until ∼10,000 ya, followed by a pronounced growth surge over the past 400 years. Adaptive selection signatures highlight genes linked to immune response (IGH cluster), lipid metabolism (FADS1/2), wound healing (TMEM121), and environmental adaptation (ABCC11), suggesting dietary shifts and tropical pathogens as key evolutionary drivers. Furthermore, the ZUN genetic profile reflects their role as a regional hub for gene flow into neighboring populations, coinciding with Han migrations during the Qin dynasty. Together, these results identify the Zhuang as descendants of Baiyue populations with a distinctive dual ancestry shaped by Neolithic southern and northern East Asians.
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