Molecular Biology And Evolution[JOURNAL]
Sun
200 papers
Genome-wide SNP data reveal hidden hierarchical population structure and demographic history of endangered black-and-white snub-nosed monkeys (Rhinopithecus bieti).
Li Y, Xu Z, Jiang Y … +7 more , Chen M, Li Y, Liu F, Luo J, Feng J, Kuang W, Yu L
Mol Biol Evol · 2026 May · PMID 41993021 · Full text
The endangered black-and-white snub-nosed monkey (Rhinopithecus bieti), endemic to high-altitude forests in southwest China, has increased from fewer than 1,500 individuals pre-1990 to over 3,500 post-2010. However, it f...
The endangered black-and-white snub-nosed monkey (Rhinopithecus bieti), endemic to high-altitude forests in southwest China, has increased from fewer than 1,500 individuals pre-1990 to over 3,500 post-2010. However, it faces severe habitat fragmentation, with at least 20 isolated groups. A comprehensive investigation of large-scale population genomic analysis is lacking. We present the first comprehensive genomic reassessment of this species using fecal-DNA and targeted capture sequencing to generate genome-wide single-nucleotide polymorphism data for 309 individuals. We identified five distinct genetic populations (Southwest, Southeast, Central, North-Central, and North) with strong geographic associations. Furthermore, we found previously unrecognized subpopulations, primarily associated with isolation within human-altered landscapes. Roads and human settlements were the primary barriers to contemporary genetic connectivity. Genetic diversity is highest centrally and declines peripherally, reflecting historical/recent barriers. Demographic inference suggests: (i) a possible southwestern origin and northward dispersal at ∼128.5 to 8.2 ka, probably driven by late Pleistocene climatic oscillations and local refugia; (ii) major subpopulation divergences within the last ∼610 to 120 years ago, likely due to human exploitation; and (iii) a sharp decline ∼300 years ago, leaving extremely low effective population size (40 to 314). Admixture origins of both Southeast and North-Central populations highlight their role in facilitating gene flow. Historically, habitats with high connectivity contrast with current severe fragmentation, particularly in the southern regions; this persistent suitability disparity suggests limited historical connectivity promoting genetic divergence between southern and central/northern populations. Our results provide critical insights into the population structure and evolutionary history of R. bieti, offering critical insights for conservation and demonstrating the power of fecal genomics in endangered species.
Adaptive evolution of odorant receptors is associated with elaborations of social organization in ants.
Pellen Y, Vizueta J, Beck E … +3 more , Liebig J, Schrader L, Privman E
Mol Biol Evol · 2026 May · PMID 41993015 · Full text
Cooperation in social insect colonies depends on complex chemical communication, requiring a large array of chemosensory receptors. Ant odorant receptors (ORs) were dramatically expanded compared to other insects, most n...
Cooperation in social insect colonies depends on complex chemical communication, requiring a large array of chemosensory receptors. Ant odorant receptors (ORs) were dramatically expanded compared to other insects, most notably in the "9-exon" subfamily, which was implicated in responding to cuticular hydrocarbons, a major class of signaling compounds. These observations indicate adaptive evolution of olfactory functions, but this process was never studied in the context of the evolution of specific sociobiological traits. The Global Ant Genomics Alliance has compiled 163 high-quality ant genomes, enabling the study of OR evolution in unprecedented detail. Analyzing 55,068 ORs across the phylogeny, we tested for association between sociobiological traits and adaptive evolution of ORs, including gene duplication and adaptive sequence evolution. We identified strong enrichment of positive selection on 9-exon ORs in the ancestor of the formicoid clade, which evolved larger colonies and greater reproductive division of labor. This result indicates a key role of chemical communication in the early evolution of complex social organization. We also observed enrichment of positive selection on 9-exon ORs associated with the recent evolution of continuous worker polymorphism in multiple lineages. Surprisingly, the evolution of other sociobiological traits was associated with reduced positive selection on ORs. These results suggest that worker polymorphism involves more extensive adaptation of chemical communication compared to other aspects of ant sociobiology. By analyzing the most comprehensive OR dataset to date, we provide new insights into the specific context in which ORs played a major role in the elaboration of social traits in ants.
Multiple losses of ecdysone receptor genes in nematodes: an alternative evolutionary scenario of molting regulation.
Yamakawa S, Barf LM, Hejnol A
Mol Biol Evol · 2026 May · PMID 41988935 · Full text
Molting is a hallmark feature of ecdysozoans, including arthropods, tardigrades, and nematodes. Ecdysone hormones play a crucial role in regulating the molting process of different ecdysozoan taxa. Interestingly, despite...
Molting is a hallmark feature of ecdysozoans, including arthropods, tardigrades, and nematodes. Ecdysone hormones play a crucial role in regulating the molting process of different ecdysozoan taxa. Interestingly, despite this highly conserved function of ecdysone, the model nematode Caenorhabditis elegans has lost the ecdysone receptor (ECR) genes and their molting appears to be ecdysone-independent. The loss of ecr has only been reported in Caenorhabditis within ecdysozoans, and the evolutionary background behind this loss has remained enigmatic. Here, we show that loss of ecr is not exceptional in Caenorhabditis, but has occurred at least 3 times in Rhabditina and Tylenchina nematodes. Our genome-wide analysis of 160 nematode species revealed multiple losses of ecr and its typical heterodimer partner usp during nematode evolution. Furthermore, using transcriptomic, pharmacological, and in silico/in vivo protein interaction analyses, we identified 2 factors that potentially underlie and buffer the loss of ECR gene/function: (i) molting regulation by an alternative nuclear receptor HR3 (NHR-23) and (ii) a lineage-specific expansion of nuclear receptors in the ecr-deficient taxa. Taken together, this study shows how key regulators of ecdysozoan molting can be altered during evolution. We propose a novel scenario for the evolution of molting regulation in nematodes.
Degeneration and adaptive evolution of digits in ratite birds.
Kang W, Wagner G, Zhou Q
Mol Biol Evol · 2026 May · PMID 41982182 · Full text
The amniote digits have undergone recurrent modifications, with the diversified molecular mechanisms more studied among mammals than reptiles. Here we focus on the emu wings and ostrich feet, both of which experienced sp...
The amniote digits have undergone recurrent modifications, with the diversified molecular mechanisms more studied among mammals than reptiles. Here we focus on the emu wings and ostrich feet, both of which experienced species-specific digit changes driven respectively by secondary flight loss and adaptation to running. By comparing their digit transcriptomes to those of chicken and alligator, we identified different gene networks in skeleton/muscle development responsible for the degenerated digits in archosaur ancestors and emu, but those in epidermal development for the load-bearing digit of ostrich. These results provide new clues for developmental programs of different cell types between different digits, on which natural selection can convergently operate.
DiagnoDating: diagnostics for dated phylogenies in microbial population genetics.
Didelot X, Carson J, Ribeca P … +1 more , Volz E
Mol Biol Evol · 2026 Apr · PMID 41978338 · Full text
Microbial population genetic studies often involve the use of a dated phylogeny to show how the genomes are related over a relevant timescale. Many tools have recently been developed to date the nodes of a standard phylo...
Microbial population genetic studies often involve the use of a dated phylogeny to show how the genomes are related over a relevant timescale. Many tools have recently been developed to date the nodes of a standard phylogeny, but all make underlying assumptions that may not be realistic for a given dataset, making the results potentially unreliable. Model comparison is sometimes used to remedy this issue, whereby inference under several models is compared to establish which result can be trusted. Although such comparison is clearly useful to assess the relative merits of several inference attempts, here instead we focus on the problem of evaluating how good an inference is in absolute terms, without comparison. We consider several approaches for diagnosing potential issues in a reconstructed dated phylogeny, including outlier detection, posterior predictive checking and residual analysis. These methods are well-established diagnostics tools in other areas of statistics, but here we show how they can be applied to the specific inference of dated phylogenies. We illustrate their use on many simulated datasets, with inference being performed either from the correct model to quantify the specificity or from an incorrect model to quantify the sensitivity of the diagnostics methods. We also applied the methods to three real-life datasets to showcase the range of issues that they can detect. We have implemented the methods in a new R package entitled DiagnoDating. We advocate the use of these diagnostics tools for all microbial population genetic studies that involve the reconstruction of a dated phylogeny.
Evolution in metazoans of the TRPM channel family involves multiple gains and losses of genes and domains.
Morini M, Bergqvist C, Asturiano JF … +2 more , Dufour S, Larhammar D
Mol Biol Evol · 2026 May · PMID 41968578 · Full text
Transient receptor potential (TRP) ion channels of the melastatin family (TRPM) have eight members in mammals with a broad spectrum of functions. We investigated the evolution of this complex gene family across metazoans...
Transient receptor potential (TRP) ion channels of the melastatin family (TRPM) have eight members in mammals with a broad spectrum of functions. We investigated the evolution of this complex gene family across metazoans. The characteristic aminoterminal melastatin domain and the carboxyterminal NUDT9 homology domain with similarity to ADP-ribose pyrophosphatase were added to the common ancestor of TRPM and its sister channel TRPS. Gene duplications before the origin of bilaterians resulted in four TRPM genes: α, β, βlike, and γ. The two latter were discovered in this study. All four and TRPS are present in extant mollusks, while differential losses occurred in the other animal lineages. TRPS, TRPMβlike, and TRPMγ were lost in early chordates, meaning that the vertebrate ancestor started with TRPMα and β, both of which were duplicated before the first vertebrate tetraploidization 1R. The ancestor of the micro-RNA genes mir-211 and mir-204 was inserted in an intron of the ancestor of TRPM1/TRPM3. The TRPM6/TRPM7 ancestor acquired a kinase domain, probably a copy of the syntenic alpha protein kinase ALPK2/3 ancestor gene. Vertebrate 1R and gnathostome 2R together with local gene duplication and losses resulted in eight TRPM (TRPM1 to 8) in the gnathostome ancestor. In cyclostomes, extensive gene losses after the hexaploidization led to four TRPM. The teleost-specific tetraploidization 3R generated further TRPM ohnologs. The NUDT9 homology domain is retained in TRPM2 and TRPS but was lost repeatedly during TRPM evolution. Thus, the TRPM family displays considerable evolutionary variation with regard to gene and domain gains and losses.
Segmental copy number amplifications are more stable than aneuploidies in the absence of selection.
De T, Ben Nun N, Spealman P … +5 more , Suresh I, Avecilla G, Abdul-Rahman F, Ram Y, Gresham D
Mol Biol Evol · 2026 Apr · PMID 41968576 · Full text
Copy number variants (CNVs) are DNA duplications and deletions that cause genetic variation, underlying rapid adaptive evolution. CNVs often confer selective advantages but can also incur fitness costs. Evolution of Sacc...
Copy number variants (CNVs) are DNA duplications and deletions that cause genetic variation, underlying rapid adaptive evolution. CNVs often confer selective advantages but can also incur fitness costs. Evolution of Saccharomyces cerevisiae in nutrient-limited chemostats recurrently selects for amplifications of nutrient transporter genes. However, their fate upon return to a non-selective environment remains unknown. To investigate CNV fitness and stability upon removing the original selection pressure, we studied 15 CNV lineages (11 segmental and 4 whole-chromosomal amplifications) selected in nitrogen-limited chemostats. CNV stability was monitored using fluorescent reporters during propagation in nutrient-rich batch cultures for 110 to 220 generations. All aneuploid lineages showed rapid CNV loss and reversion to a single-copy genotype, whereas segmental amplifications were remarkably stable; one of the 11 strains reverted. Pairwise fitness competitions in rich media revealed strong fitness defects associated solely with CNVs that reverted; reversion led to increased fitness. Using simulation-based inference to estimate reversion rates and fitness effects, we determined negative selection as the primary driver of CNV loss. Whole-genome sequencing revealed that reversion of aneuploids and a segmental amplification left no evidence of prior CNV existence, rendering revertant genomes indistinguishable from the single-copy ancestor. Detailed characterization of a partial revertant identified chromosomal translocation, suggesting that extant CNVs can undergo structural diversification. Our findings provide novel evidence that most segmental CNVs adapted to nitrogen limitation are stable upon removal of selection, but costly gene amplifications are readily reversible. Together, these highlight the importance of CNVs in both long-term genome evolution and rapid, reversible adaptation to transient selection.
AliFilter: a machine learning approach to alignment filtering.
Bianchini G, Zhu R, Cicconardi F … +1 more , Moody ERR
Mol Biol Evol · 2026 Apr · PMID 41967463 · Full text
Multiple sequence alignments are a crucial step in many bioinformatic and computational biology analyses, from protein structure and function prediction to the inference of phylogenetic trees. However, highly divergent s...
Multiple sequence alignments are a crucial step in many bioinformatic and computational biology analyses, from protein structure and function prediction to the inference of phylogenetic trees. However, highly divergent sequence alignments often contain a significant amount of noise. Reducing noise is normally achieved by filtering the alignment to remove columns that are poorly aligned or offer minimal useful information-either automatically using various software tools or through manual inspection. Manual approaches are labor-intensive and less reproducible but can utilize the researcher's specialist knowledge, rather than relying on filtering criteria that might not be adequate for each alignment. AliFilter bridges these two approaches to alignment curation, using machine learning to automate manual alignment filtering. AliFilter uses a supervised learning approach to create a model from a small number of manually annotated alignments, then applies this model to reproduce the manual annotation on different datasets. Users can employ the program with a default model or create customized models for individual datasets or filtering criteria. AliFilter accurately reproduces the results of manual annotation (98% accuracy) while being resilient to mistakes in the training data. In a typical phylogenomic workflow, AliFilter reduced the runtime by 35% and produced results that were almost identical to the full alignment, unlike other filtering tools we tested. AliFilter is free and open-source software; it is written in C# and distributed under a GPLv3 license from https://github.com/arklumpus/AliFilter, where both the source code and standalone executables for Windows, macOS, and Linux are available.
Benchmarking imputation accuracy in the presence or absence of a reference panel.
Topaloudis A, Cumer T, Lavanchy E … +8 more , Hewett A, Bachmann Salvy M, Ducrest AL, Simon C, Almasi B, Roulin A, Delaneau O, Goudet J
Mol Biol Evol · 2026 Apr · PMID 41967458 · Full text
Whole genome sequencing (WGS) of a large number of samples is costly. Solutions include targeting a proportion of the genome (eg SNP arrays) or lowering the sequencing depth (low-coverage WGS, lcWGS) but both approaches...
Whole genome sequencing (WGS) of a large number of samples is costly. Solutions include targeting a proportion of the genome (eg SNP arrays) or lowering the sequencing depth (low-coverage WGS, lcWGS) but both approaches suffer from either genotype missingness or uncertainty. Genomic imputation addresses this problem by inferring missing or uncertain genotypes using a collection of high quality genomic data (reference panel). However, certain methods can impute a lcWGS dataset without a reference panel. Because generating a reference panel can be prohibitively expensive in nonmodel species, a benchmarking of the accuracy of these alternative methods of imputation can help inform study design. Here, we imputed a dataset of 2,800 barn owls (Tyto alba) sequenced in lcWGS in the presence and absence of a reference panel of 502 samples. We used 32 individuals sequenced at both high and low coverage to estimate the accuracy of each method and explored the limitations of lcWGS sample size and reference panel size. Although the best results were achieved with a large reference panel, using only a lcWGS dataset showed very accurate imputation, when over 500 samples were used and we account for missing data and low frequency alleles. In addition, imputation with or without a reference panel returned similar results in a GWAS of a polygenic trait but caution was required when comparing identified homozygous-by-descent segments. Thus, while using a reference panel remains the ideal approach, imputation in suitably large lcWGS datasets can provide sufficient accuracy given proper quality control.
Phylogenomic mixture models outperform homogeneous and partitioned models.
Pisani D, Giacomelli M, Szöllősi GJ … +3 more , Rossi ME, Domènech M, Lozano-Fernandez J
Mol Biol Evol · 2026 May · PMID 41967133 · Full text
Significant advances have been made in resolving the tree of life, but many nodes remain debated. The last two decades saw the emergence of mixture models, which proved particularly useful to account for across-site comp...
Significant advances have been made in resolving the tree of life, but many nodes remain debated. The last two decades saw the emergence of mixture models, which proved particularly useful to account for across-site compositional heterogeneity, and played a central role to improve our understanding of difficult phylogenetic problems. However, some scholars have remained skeptical of their use. Here, we perform a large simulation study comparing mixture models accounting for across-site compositional heterogeneity, across-site compositionally homogeneous models and partitioned models. We show that the tested mixture models fit across-site compositionally heterogeneous datasets best and achieve greater accuracy. Of the tested models, CAT-GTR, an infinite mixture model combining a general time reversible-GTR-matrix with a mixture of site-frequency profiles (i.e. categories-CAT-or components) characterized by different amino acid frequency vectors, maximizes accuracy and fit. Mixture models, and particularly CAT-GTR, perform well also with across-site compositionally homogeneous datasets, where the use of a mixture of site-frequency profiles is not necessary. We show that this is because with homogeneous data these models converge to appropriate compositionally homogeneous models, avoiding overparametrization. Our results dissipate doubts about the utility of models accounting for compositional heterogeneity across sites and identify CAT-GTR as one of the most flexible models in the phylogenomic arsenal.
Comparative phenotypic analysis of rhodopsin supports stepwise evolution of dim-light vision in early vertebrates.
Cui Y, Lu X, Wei P … +9 more , Shuai M, Sun L, Xie Y, Xie Y, Dong R, Shi L, Rossiter SJ, Xu S, Liu Y
Mol Biol Evol · 2026 Apr · PMID 41967125 · Full text
The origin of dim-light vision in vertebrates has been attributed to an early duplication event in an ancestral form of pigment called RH, which led to the formation of the RH1 (rhodopsin) and RH2 (rhodopsin-like) opsins...
The origin of dim-light vision in vertebrates has been attributed to an early duplication event in an ancestral form of pigment called RH, which led to the formation of the RH1 (rhodopsin) and RH2 (rhodopsin-like) opsins. Two sites (122 and 189) are known to critically underlie rhodopsin's sensitivity in low light; however, the evolutionary trajectory leading to dim-light vision remains unclear. We built a large comparative dataset of vertebrate RH1 and RH2 sequences and inferred their respective ancestral protein sequences alongside their common ancestor. Sequence comparisons revealed that known critical sites underpinning RH1 kinetics did not evolve at the origin of this molecule, and instead first evolved in RH (M122E) as well as later in the RH1 of ancestor of jawed vertebrates (P189I). To assess the phenotypic impacts of these changes, we conducted in vitro protein expression and found that the retinal release rate of RH1 became significantly slower following its divergence from RH2, with further deceleration at the origin of jawed vertebrates. We also constructed single RH1 mutants and found that the replacement S295A accounted for the observed difference in retinal release between RH and RH1. Finally, to validate these phenotypic consequences in vivo, we compared zebrafish overexpressing RH, RH1, or the mutant RH-S295A, and recorded increased locomotor rebound following light-intensity reduction in the latter two treatments. We conclude that highly sensitive dim-light vision in vertebrates evolved via three main stages of molecular adaptation, at the origins of RH and RH1, and subsequently in the ancestral RH1 of jawed vertebrates.
Pangolin museum genomics reveal the dynamic genetic consequences and extinction risk of the critically endangered Chinese pangolin.
Hu JY, Jiang Y, Li S … +2 more , Ying TT, Yu L
Mol Biol Evol · 2026 May · PMID 41967090 · Full text
Human-driven biodiversity loss, intensified by illegal hunting and trafficking, has caused severe wildlife population declines and extinctions, necessitating studies on long-term genomic erosion to inform conservation st...
Human-driven biodiversity loss, intensified by illegal hunting and trafficking, has caused severe wildlife population declines and extinctions, necessitating studies on long-term genomic erosion to inform conservation strategies. While temporal genomic analyses using ancient and historical/museum DNA reveal generational impacts, sparse sampling often limits insights into prolonged declines, highlighting the need for time-resolved studies to understand sequential population decline and species persistence under sustained pressures. The Chinese pangolin (Manis pentadactyla), critically endangered as a result of historical overexploitation, has experienced severe continuous population decline pre-1979, 1980-1999, and post-2000. However, the temporal genetic consequences and associated extinction risks remain poorly understood. We analyzed 228 pangolin genomes (133 newly sequenced), spanning continuous population decline, to assess the dynamics of genomic erosion. Our results demonstrate that persistent population decline drives long-term genetic decline within populations, with the severity of population decline correlating directly with the degree of negative genetic impact (e.g. reduced diversity, increased inbreeding and genetic load) and extinction risk. Counterintuitively, however, between populations, those experiencing the most severe population decline (e.g. southwest China) exhibited less extreme relative genetic consequences compared to less severe population decline (e.g. south China), suggesting a stronger dependence on the history of effective population size before population decline. Critically, the contemporary South China population shows significantly lower genetic diversity, higher inbreeding, elevated genetic load, and consequently higher extinction risk, demanding urgent prioritization for conservation. This study provides novel insights into the complex genomic legacy of continuous population decline, elucidating anthropogenic impacts on genetic erosion and offering a scientific framework for targeted conservation strategies.
Deep learning reveals genomic regions introgressed between two recurrently hybridizing lynx species.
Bazzicalupo E, Lorenzo-Fernández L, Mayor-Fidalgo L … +3 more , Soriano L, Schrider DR, Godoy JA
Mol Biol Evol · 2026 Apr · PMID 41964531 · Full text
Recently, diverged species with overlapping distributional ranges have high chances of hybridizing and if hybrids are viable, genomic material can be transferred between species in a process called introgression. To char...
Recently, diverged species with overlapping distributional ranges have high chances of hybridizing and if hybrids are viable, genomic material can be transferred between species in a process called introgression. To characterize the patterns and consequences of introgression in species with historically low population sizes and recent steep declines resulting in genetic erosion, we analyze the Iberian and Eurasian lynx (EL) as an illustrative and relevant case study. While genome-wide introgression was already detected, here we apply a method using a deep convolutional neural network to detect specific regions of the genome with signals of introgression in three populations of these two species. Over 6% of the genome of both Iberian lynx and ELw shows introgression from the other species, compared with only 2% in the ELs. This observation, along with the results from demographic modeling, suggests that the ELw population is genetically closest to the source of EL introgression, a probably now extinct group that coexisted with the Iberian lynx in Southern Europe and Northern Iberia until recently. As predicted by theory, introgression was generally higher in populations with smaller effective sizes and in genomic regions of high recombination. However, the Iberian lynx did not show higher overall introgression than the more abundant ELw, and coding regions introgressed as frequently as intergenic regions. Local genetic diversity is boosted approximately 3-fold in genomic windows where introgression occurs, potentially including the adaptively relevant and highly diverse MHC region of the Iberian lynx.
Wnt signaling patterns a central-peripheral body axis in the early-diverging metazoan Trichoplax adhaerens.
Di G, Jin M, Li W … +3 more , Yuan M, Zhang Y, Zhao C
Mol Biol Evol · 2026 Apr · PMID 41964527 · Full text
Body axis formation was a pivotal innovation in animal evolution, providing the spatial framework necessary for organized multicellularity. While the genetic basis of axis specification is well established in bilaterians...
Body axis formation was a pivotal innovation in animal evolution, providing the spatial framework necessary for organized multicellularity. While the genetic basis of axis specification is well established in bilaterians, how axial organization emerged in early-diverging metazoans remains unresolved. Here, we address this question in Trichoplax adhaerens, a placozoan representing one of the simplest extant animal body plans. We show that Wnt signaling, a conserved regulator of axial patterning, exhibits polarized expression enriched in the peripheral region of this morphologically simple organism. Functional perturbations demonstrate that Wnt activity promotes peripheral cell proliferation and maintains central-peripheral tissue balance. Transcriptomic profiling further reveals distinct molecular identities along this axis, resembling the oral-aboral polarity of cnidarians. Together, our findings uncover a Wnt-dependent axial system in placozoans and support the view that core components of metazoan body axis patterning were already established in early animal evolution.
Revealing deep evolutionary relationships between RNA viruses using predicted structural models of viral RNA polymerases.
Mönttinen HAM, Ravantti JJ, Mayne R … +2 more , Simmonds P, Poranen MM
Mol Biol Evol · 2026 Apr · PMID 41950502 · Full text
The RNA-dependent RNA polymerase (RdRP) is the only homologous gene shared among current members of the kingdom Orthornavirae in the realm Riboviria. It is therefore used as a hallmark gene to infer their evolutionary re...
The RNA-dependent RNA polymerase (RdRP) is the only homologous gene shared among current members of the kingdom Orthornavirae in the realm Riboviria. It is therefore used as a hallmark gene to infer their evolutionary relationships and to guide their taxonomic classification. While sequence similarity between RNA viruses is often limited and sequences problematic to align, the conservation between the three-dimensional tertiary structures of viral RdRPs is notable, supporting analysis of deep evolutionary relationships. Nevertheless, the limited availability of experimental RdRP structures restricts structure-based phylogenetic analyses. We used the protein structure prediction algorithm AlphaFold to alleviate this restriction and predicted structure models for 989 viral RdRPs. Through structural alignment with Homologous Structure Finder, we identified 211 structurally equivalent residues for RdRPs, representing 96 virus genera recognized by the International Committee on Taxonomy of Viruses. These equivalent residues were used to deduce a comprehensive structure-based phylogenetic tree for viral RdRPs, which was validated using a jackknifing approach developed in this study. For comparison, structural phylogenies were inferred using alignments produced with FoldTree and FoldMason software. The resulting trees mostly support the current taxonomic assignments of RNA viruses at the class rank. However, they do not support the monophyly of phyla Pisuviricota and Duplornaviricota. Furthermore, flaviviruses frequently group apart from other members of Kitrinoviricota. The conservation of protein structures over long periods of evolutionary time, when detectable sequence homology may be lost and sequence alignment problematic, supports the use of protein structure comparison methods for demonstrating the deeper evolutionary histories of RNA viruses.
Integrated conjugative elements drive the formation of pandemic clones of Escherichia coli with hybrid chromosomes.
Berruga-Fernández T, Huseby DL, Koshla O … +5 more , Shaukat A, Katana A, Sayed R, Marino G, Hughes D
Mol Biol Evol · 2026 Apr · PMID 41950494 · Full text
Pathogenic multidrug-resistant bacteria with hybrid chromosomes have emerged as a significant global healthcare threat. These include the pandemic Escherichia coli ST1193, the product of homologous recombination events i...
Pathogenic multidrug-resistant bacteria with hybrid chromosomes have emerged as a significant global healthcare threat. These include the pandemic Escherichia coli ST1193, the product of homologous recombination events involving two phylogenetically distant strains of E. coli, in which mutant alleles of the widely separated genes, gyrA and parC, generating high-level fluoroquinolone resistance were acquired. The mechanisms and frequency of hybrid formation are poorly understood. We developed a robust hybrid selection procedure and applied it to 118 clinical UTI isolates of E. coli mixed with suitable recipient strains. Hybrids were selected from 39% of isolates. All hybrids were recombinants of donor and recipient chromosomal DNA (median length of donor DNA 367 kb), with 90% also acquiring conjugative mobile genetic elements (MGE) from the donor. We showed that individual conjugative plasmids, and integrative conjugative elements (ICE), from donors were sufficient to drive hybrid formation. These observations strongly support conjugative chromosomal DNA transfer as the major mechanism underlying hybrid formation. ICE are genome-integrated and passively propagated but when transferring to recipients they normally do so by excising and producing their own conjugation machinery. We found that ICE were responsible for the highest frequencies of hybrid chromosome formation. They could mobilize DNA around the full length of the chromosome, including the simultaneous acquisition of mutant variants of gyrA and parC, separated by ∼826 kb, generating highly fluoroquinolone-resistant bacteria in a single event. Bacterial hybrid chromosome formation driven by conjugative MGE may be an important and widespread mechanism in the emergence and evolution of high-risk bacterial pathogens.
A new super-pangenome pipeline reveals domestication signatures of conserved noncoding sequences in the orange subfamily.
Tan L, Zhu S, Ye J … +1 more , Jiao WB
Mol Biol Evol · 2026 Apr · PMID 41949280 · Full text
Advances in genome sequencing have accelerated the assembly of hundreds of plant genomes. Because of limited tools, current pangenome approaches overlook conserved noncoding sequences, though these sequences potentially...
Advances in genome sequencing have accelerated the assembly of hundreds of plant genomes. Because of limited tools, current pangenome approaches overlook conserved noncoding sequences, though these sequences potentially harbor diverse regulatory elements. Here, we present panCG, an integrative pipeline for family level super-pangenome analysis across coding and noncoding sequences. PanCG enables the reference-free construction of pangene and pan-conserved noncoding sequences (panCNS) indices and integrative analyses between them. Applying this pipeline to the orange subfamily (Aurantioideae) with 22 representative genomes, we identified 167,989 panCNSs, 44.63% of which exhibited potential functionality, as evidenced by multiomic data (eg ATAC-seq, ChIP-seq). Functionally, approximately half of duplicated genes showed expression divergence, likely mediated by sequence variants in these panCNSs. Although transposable element (TE) mobilization resulted in substantial CNS loss, it also contributed to the origin of a small portion of functional CNSs. By integrating panCNS and pangene data, we identified 1,391 conserved colocalized blocks of CNSs and genes across all selected genomes, providing clear evidence for coevolution between CNSs and their target genes. Notably, leveraging these pan-genomic resources, we pinpointed numerous CNSs and gene-CNS regulatory modules as candidates underlying the domestication of citrus fruit traits from wild relatives. Our study presents a powerful tool for interspecific super-pangenome analysis, whereas shedding new light on the functional roles and evolutionary dynamics of CNSs in citrus, and provides a valuable resource of candidate regulatory elements for citrus fruit biology and breeding research.
Transgenerational effects of heat shock on gene regulation and fitness-related traits in natural Drosophila populations.
Harney E, González J
Mol Biol Evol · 2026 Apr · PMID 41949279 · Full text
Heat stress will increasingly affect populations as climate change leads to higher temperatures and more frequent heat waves. Recent work suggests that interactions between the epigenome and transposable elements (TEs) c...
Heat stress will increasingly affect populations as climate change leads to higher temperatures and more frequent heat waves. Recent work suggests that interactions between the epigenome and transposable elements (TEs) could link environmental acclimation with rapid evolution. Yet little is known about how these processes interact in natural genetic backgrounds or shape evolutionarily relevant phenotypes. To investigate these interactions, we carried out laboratory experiments measuring gene expression and chromatin accessibility responses to heat shock in female D. melanogaster from arid and cold climates, their associations with population variation in TEs, and fitness-related phenotypes including viability and development time in the offspring. We also measured expression, accessibility and phenotypic traits three generations later to explore transgenerational inheritance. Expression and accessibility responses to heat shock varied between populations and were influenced by TE presence, with more upregulated responses in the arid population. Effects of heat shock on transcription were detected three generations later, especially in the arid population, although this was not driven by chromatin accessibility. Among offspring of heat shocked flies, phenotypes of the initial cohort (eggs laid within 2 d of heat shock) were negatively affected in both populations, but later cohorts (eggs laid more than 2 d after heat shock) from the arid population developed quicker than controls, indicating hormesis. This effect was still present four generations after the heat shock in the great-great-grandoffspring, demonstrating transgenerational inheritance of potentially beneficial phenotypes and gene expression in a natural insect population.
Conservation and divergence of sex-biased gene expression across 50 million years of Drosophila evolution.
Glaser-Schmitt A, Parsch J
Mol Biol Evol · 2026 Apr · PMID 41947595 · Full text
In sexually dimorphic species, sex-biased gene expression plays an important role in driving morphological, physiological, and behavioral differences between males and females. Here, we examined patterns of sex-biased ge...
In sexually dimorphic species, sex-biased gene expression plays an important role in driving morphological, physiological, and behavioral differences between males and females. Here, we examined patterns of sex-biased gene expression within and among 6 Drosophila species with divergence times ranging from 2 to 50 million years. We detected contrasting patterns of sex bias conservation and turnover between heads and bodies, with more extensive sex-biased expression and greater conservation of sex-biased expression in the body, but more species-specific turnover of sex-biased expression in the head, where conserved, unbiased expression was common. Interestingly, lineage-specific gains of sex-biased expression occurred most often via concordant expression changes in both sexes that differed only in their magnitude, with this pattern being particularly strong in the head, suggesting that the majority of lineage-specific sex bias gains do not represent a resolution of sexual antagonism, but instead reflect regulatory changes shared between the sexes. We detected an enrichment of putatively positively selected expression changes among sex-biased genes in both body parts. Altogether, our findings suggest that sex-biased expression changes are often facilitated by selection, including selection acting on the sex with lower expression, which is especially common for male expression of female-biased genes. We also detected differences in the proportion of sex-biased genes located on the X chromosome depending on sex bias and body part. Overall, our results provide novel insights into the dynamics of sex-biased gene expression, as well as the molecular mechanisms and selective forces underlying its turnover, across short and long evolutionary timescales.
A key regulator of missing-self innate immunity is polymorphic and under diversifying selection.
Notarnicola RF, Herdegen-Radwan M, Różańska-Wróbel J … +5 more , Konczal M, Przesmycka K, Kotlík P, Babik W, Radwan J
Mol Biol Evol · 2026 Apr · PMID 41947593 · Full text
Host-parasite co-evolution drives the diversification of host immune genes involved in the recognition of pathogen antigens and molecular patterns. In contrast, the immune genes involved in self-recognition and inhibitio...
Host-parasite co-evolution drives the diversification of host immune genes involved in the recognition of pathogen antigens and molecular patterns. In contrast, the immune genes involved in self-recognition and inhibition of immune responses against self-cells (missing-self immunity) may be evolutionarily constrained by the need to interact with self-components. However, many pathogens, such as the Lyme disease agent Borrelia, hijack these genes to evade the immune system and may therefore select for their diversification. How these contrasting but concurrent selective forces shape the evolution of missing-self regulators is not clearly understood. To fill this gap, we investigated polymorphism and molecular signatures of selection acting on a missing-self regulator, the complement factor H (CFH), in bank vole populations, which are an important wild reservoir for Borrelia. We then compared the geographic structuring in the CFH domain interacting with Borrelia (CCP 20) against a genomic background represented by RAD-seq markers. We found signals of positive and diversifying selection at CCP 20, suggesting that CFH evolved in response to pressures from pathogens. Additionally, we found other innate immunity genes within the alternative complement pathway, which is regulated by CFH, under diversifying selection, highlighting its involvement in host-parasite coevolution. This study demonstrates that an innate missing-self sensor in a wild vertebrate is under diversifying selection, likely driven by pathogens.
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