BMC Evolutionary Biology

Body size, through its links to various physiological traits, has often been hypothesized to influence evolutionary rates. Negative body size-rate correlations have been reported in the morphological or molecular evolution of several extant vertebrate groups, including mammals, birds, reptiles, and teleost fishes. In this study, we estimated body masses for 89 species of plesiosaurs, a clade of Mesozoic aquatic reptiles, and found that their body size evolution conforms to a three-regime Ornstein-Uhlenbeck process, indicative of constrained evolution. Rates of morphological evolution, inferred using the skyline fossilized birth-death process and the variable-rates model, show minimal support for a correlation with body size in this clade. Our results thus serve as a counterexample, suggesting that the negative body size-rate relationship is not a universal vertebrate pattern, but rather a trend restricted to certain lineages.

Arthropods exhibit an exceptional diversity of life histories, where developmental modes involve moulting stage progressions with changes ranging from the bare minimal to the dramatically transformative. While this variability drives many research questions aiming to understand evolutionary and developmental underpinnings of life history differences, it can complicate comparative analyses across taxa. However, this can be approached by applying a framework that defines metamorphosis as a post-embryonic stage progression characterised by substantial changes in morphology and adaptive landscape. Employing this framework with a phylogenomic dataset spanning 26 orders and encompassing four independently arising metamorphic lineages, we explore gene repertoire evolutionary dynamics potentially associated with metamorphosis in Pancrustacea. The approach contrasts gene family evolutionary dynamics inferred to have occurred in the last common ancestors of the metamorphic Insecta, Copepoda, Eucarida, and Thecostraca, with those of their sister lineages, as well as of descendent and ancestral nodes. The results reveal that the metamorphosis ancestors are characterised by an elevated number of gene family births and expansions. Expanded gene families share a set of commonly enriched biological processes across all metamorphosis ancestors, suggesting functional convergence by independent evolution of distinct gene families involved in embryonic and post-embryonic development and nervous system differentiation. Evolutionary modelling further highlights a subset of these families exhibiting signatures of adaptive, lineage-specific gene family size increases associated with metamorphic development. These families include genes implicated in neural and sensory development, segmentation, and moulting. These findings support a model of the evolution of pancrustacean metamorphosis where distinct gene families from a common functional toolkit expand and are co-opted into facilitating transitions to multi-phasic life cycles. This reframes the role of moulting in arthropod diversification to be recognised as an important reservoir of genetic change that can potentiate truly remarkable life history transitions.

Molecular phylogenetics based on primary sequence comparisons has been central to reconstructing protein evolution. However, structural evolution does not necessarily parallel sequence divergence, particularly in proteins combining ordered domains with intrinsically disordered regions (IDRs). Here, we introduce a quantitative secondary structure distance (S2D) metric that enables systematic comparison of protein secondary structure, including both ordered elements and IDRs. Using the MADS-box transcription factor family as a model, we show that structural divergence is domain-specific and only partially coupled to sequence-based phylogeny. Domain-resolved analyses reveal that the DNA-binding M domain remains structurally constrained, whereas the I and C domains exhibit extensive sequence divergence while retaining conserved intrinsic disorder. In contrast, the K domain contributes disproportionately to global structural variability. Integrating S2D with phylogenetic distance uncovers both convergent structural architectures among distantly related proteins and pronounced structural remodelling within closely related paralogs--patterns not evident from primary sequence comparisons alone. Residue-level analyses further demonstrate that the structural impact of mutation depends strongly on amino acid identity and does not scale directly with substitution frequency or conservation metrics. Together, these findings indicate that secondary structural evolution provides an additional dimension of protein diversification beyond sequence divergence. By integrating phylogenetic and structural distances, this framework offers a complementary approach to interpreting protein evolution, particularly in families containing mixtures of ordered domains and intrinsically disordered regions. Significance StatementEvolutionary relationships are typically inferred from primary sequence comparisons, yet structural evolution may follow different trajectories. By developing a quantitative measure of secondary structural divergence, we show that structural change within the MADS-box transcription factor family can both converge and diverge independently of sequence-based phylogeny. Intrinsically disordered regions exhibit extensive sequence divergence while retaining conserved disorder, whereas specific amino acid substitutions disproportionately reshape secondary structure. These findings demonstrate that evolutionary diversification operates through domain-specific structural modulation rather than uniform sequence divergence. Integrating structural and phylogenetic distances provides a complementary framework for interpreting protein evolution and reveals evolutionary patterns that remain hidden when relying on sequence comparisons alone.

Protein evolutionary rates vary widely across proteins and among sites within proteins, reflecting multiple molecular, cellular, and functional constraints. While protein-level properties, such as expression and essentiality, and site-level structural and functional constraints, are known to influence evolutionary rates, how these constraints combine across scales to determine site-specific evolutionary rates remains unclear. Moreover, because many protein features are strongly correlated, it is difficult to disentangle their individual contributions to evolutionary rate variance, and unified predictive models that integrate these properties are still lacking. Here, we use neural networks to predict protein evolutionary rates across multiple scales based on multiple molecular and cellular features. At the protein level, integrating molecular and cellular descriptors explains substantial variance in evolutionary rates across proteins in multiple eukaryotic species, including nearly 50% of the variance in humans and substantial fractions of the variance in other eukaryotic species. The model also allows us to identify proteins whose evolutionary rates deviate from expectations based on their molecular and cellular properties. At the site level, we found that structural and functional features explain a comparable fraction of the variance in relative evolutionary rates. By integrating protein-level and site-level predictors, the model explains up to 37% of the variance in site-specific evolutionary rates across proteins. Our analysis demonstrates that constraints at these two scales combine largely additively, with protein-level properties setting the overall evolutionary context and site-level properties shaping variation within proteins. Together, these results provide a quantitative framework for understanding protein evolution across biological scales.

The ratio of nonsynonymous to synonymous substitution rates ({omega}) constitutes a fundamental parameter for inferring adaptive protein evolution, predicated upon the assumption that synonymous substitutions are selectively inert. This premise, however, is increasingly untenable given evidence of selection acting on synonymous substitutions, driven by various biological processes such as translational efficiency and mRNA stability. In this study, we demonstrate that unmodelled synonymous selection introduces substantial bias into{omega} estimation, resulting in elevated false positive rates in tests for positive selection. To rectify this, we present BUSTED+S+MSS, a statistical framework incorporating Multiclass Synonymous Substitution (MSS) models into BUSTED, a method for detecting episodic selection. By partitioning synonymous codons into empirically derived rate classes, this approach accounts for global synonymous constraints. Application to five diverse clades--Drosophila, Caenorhabditis, Enterobacteria, Saccharomyces, and Primates--reveals that the inclusion of MSS components consistently improves model fit and reduces the proportion of genes inferred to be under positive selection. In Enterobacteria, genes retaining significance under the corrected model exhibit weaker constraint on synonymous substitutions (dSs), consistent with the hypothesis that unmodelled purifying selection drives spurious signals of adaptation. Furthermore, an information-theoretic analysis indicates that whilst site-specific variation (SRV) provides the primary correction, global synonymous rate variation (MSS) contributes a distinct second-order correction. In highly divergent alignments, these signals act in concert to improve model fit. The BUSTED+S+MSS framework, especially when coupled with an "error-sink" to absorb alignment artifacts, thus offers a computationally feasible means to disentangle adaptive nonsynonymous substitution from the confounding effects of synonymous constraint.

The rhesus macaque (Macaca mulatta) is one of the most widely used animal models in biomedical research, both as it resembles humans in key biological aspects and as it is characterized by a broad geographic range. Most of the individuals housed in U.S. research colonies have been sampled from either China or India, though notably the source population of these animals has significantly shifted over time. Given the substantial genetic and immunological differences between these populations, a deeper understanding of the underlying population structure is critically important for biomedical interpretation. Despite this, the demographic histories of these two populations remain poorly resolved. Here, we present an analysis of whole-genome, PacBio HiFi long-read sequencing data from ten unrelated individuals of each population, applying four related model- and non-model based demographic inference approaches, in order to reconstruct their ancestral history. We evaluated the fit of the subsequently estimated models against the empirical data, and incorporated underlying uncertainty in the mutation rates used for scaling. We inferred a well-fitting population history characterized by substantial structure between Chinese and Indian populations, with a split time [~]140,000 generations ago from an ancestral population of [~]65,000 individuals. We additionally inferred the subsequent history of size change within, and gene flow between, these populations, reaching the current estimated sizes of [~]220,000 individuals in the Chinese population and [~]14,000 individuals in the Indian population. The robust baseline demographic model established in this study will serve as a valuable resource for future research on this species, including for improved fine-scale recombination mapping, selection inference, and association studies.

BackgroundAlpha satellites, a superfamily of AT-rich tandem repeats, are the primary DNA component of centromeres in Platyrrhini and Catarrhini. Analyses of the human genome suggest that centromeres behave like biological ridges, with new alpha satellite families expanding at the centromere core, splitting and displacing older ones towards the pericentromeres. The Cercopithecini tribe, which displays an unusual chromosomal evolution involving multiple chromosomal fissions and centromere formations, represents a promising model to enhance our understanding of alpha satellite DNA evolutionary history. We previously applied targeted sequencing to centromere DNA from two distant species drawn from the Cercopithecini terrestrial and arboreal lineages, and characterized six alpha satellite families exhibiting varying mean sequence identities. MethodsCombining classical and molecular cytogenetics, we mapped the chromosomal distribution of these alpha satellite families across 13 Cercopithecini, one Papionini, and one Colobinae species. A nuclear marker-based phylogeny provided an evolutionary framework for interpretation. ResultsOur phylogeny identifies the terrestrial and arboreal lineages, and a newly designated swamp clade. We observed significant interspecies variations in alpha satellite patterns, including differences in presence/absence and distinct chromosomal distribution patterns (centromeric, pericentromeric, or subtelomeric). Families previously described as heterogeneous (83-87% mean sequence identity) exhibit a centromeric position in the swamp lineage, which is characterized by conserved karyotypes. In contrast, these families show a pericentromeric distribution in the terrestrial and arboreal lineages, replaced at the centromere core by more homogeneous families (95-98% mean sequence identity). In the arboreal clade, which is characterized by highly fissioned karyotypes, putative evolutionary new centromeres show a unique co-occurrence of highly homogeneous and heterogeneous families. Conclusion & ImplicationsWe propose a comprehensive evolutionary scenario for alpha satellite DNA in Cercopithecini, where younger families arise at the centromere core, shift toward the pericentromeres as they age, and eventually face extinction. Our study suggests that alpha satellite DNA and chromosomes evolve in an interdependent manner, with satellite diversification and displacement occurring in parallel with chromosome fissions and centromere repositioning. This comparative cytogenomic approach provides both support for the human-based evolutionary model for alpha satellite DNA and novel temporal insights into its diversification dynamics. Beyond evolutionary genomics, our findings highlight the potential of alpha satellite DNA to complement systematic studies in deciphering complex primate evolutionary histories.

Molecular evolution is often modeled as proceeding at consistent rates over time, with some deviations accommodated by relaxed molecular clock models. Here, we quantify the full extent of variability in branch-specific substitution rates across relatively well-calibrated eukaryotic phylogenies, confirming that punctuated change at the molecular level underlies evolution at the morphological level where punctuated dynamics are more commonly recognized. We also show how inferred substitution rates decrease systematically when measured across increasing time intervals. This scale-dependence persists across alternative clock models, calibration strategies, and prior assumptions, but disappears in simulated data evolved under a constant rate - suggesting that the phenomenon arises from time-varying substitution rates and reflects genuine properties of evolutionary histories rather than model artifacts. The observed pattern is analogous to the Sadler effect in sedimentary geology, where time-averaged rates decline with increasing measurement interval because sedimentation is episodic, with longer hiatuses occurring less frequently. The recognized scale-dependent bias in molecular evolution is not captured in current molecular clock models and significantly impacts inferences of evolutionary history, such as estimating the age of Metazoa and understanding the timing and nature of the Cambrian Explosion. Significance StatementRates of molecular evolution are central to reconstructing the history of life, yet they are often assumed to be approximately constant over sufficiently long timescales. By analyzing relatively well-dated evolutionary trees of eukaryotes, we show how inferred rates of genome change systematically decrease as the timescale of measurement increases. This pattern is analogous to a well-known phenomenon in sedimentary geology where apparent sedimentation rates decline over longer intervals due to episodic processes. Our results demonstrate how long-term variability in evolutionary rates similarly produces a significant scale-dependent bias which is overlooked in current evolutionary models. Recognizing and quantifying this effect is important for dating key evolutionary events, such as the origin of animals, and for understanding the cadence of evolutionary processes.

Pleiotropic genes control multiple traits. This can result in evolutionary antagonism because adaptation that favors one trait can interfere with the function of another. While pleiotropic genes show statistical signatures of evolutionary constraint, many of them contain multiple domains that may evolve under different selective pressures. This could either strengthen or alleviate gene-level constraint. Here, we study pleiotropy within the immune system of six Drosophila species to disentangle gene and domain-level evolution. We hypothesized that the multifunctional nature of pleiotropic genes may promote within-gene variation in evolutionary rates of their domains compared to non-pleiotropic genes. Consistently, we found a greater within-gene variation in evolutionary rate among domains of pleiotropic genes than other gene classes, despite relatively low between-gene variation in evolutionary rates among pleiotropic genes. Non-pleiotropic genes, on the other hand, show a more heterogeneous selective pressure at the gene level. Regardless of pleiotropy status, domains within antiviral proteins show elevated evolutionary rates, while signaling protein domains show elevated ratios of radical to conservative amino acid substitutions, which likely have a significant effect on protein structure and function. Finally, an examination of plasticity in infection-induced gene expression responses across species revealed that non-pleiotropic genes with elevated evolutionary rates were also more likely to demonstrate variation in plasticity, but this relationship did not extend to pleiotropic genes. Overall, our results identify differences in evolutionary patterns across various biological levels (i.e., gene, domain, protein, and expression), showing that domain-specific evolution can potentially alleviate gene-level constraints.

The Down syndrome cell adhesion molecule (DSCAM) family, conserved across metazoans, plays key roles in neural development by mediating cell-cell recognition. Invertebrate Dscam evolved extensive molecular diversity through isoform diversification, whereas the vertebrate paralogs DSCAM and DSCAML1 followed a distinct evolutionary trajectory. However, how these vertebrate paralogs evolved after duplication, particularly with respect to functional divergence, remains poorly understood. Here, we investigated the evolutionary history and post-duplication divergence of these paralogs using phylogenetic, molecular evolutionary, sequence comparison, and transcriptomic analyses. Our phylogenetic analyses suggest an ancestral gene duplication predating the split between gnathostomes and cyclostomes. We found distinct patterns of selective constraint between the paralogs, particularly in the intracellular domain. In tetrapods, the intracellular domain of DSCAM showed strengthened purifying selection, whereas no comparable reinforcement was evident for DSCAML1, despite strong constraint in mammals. We also found distinct patterns of lineage- and site-specific positive selection between DSCAM and DSCAML1. Consistent with these evolutionary differences, comparative analysis of the intracellular domains revealed distinct repertoires of short linear motifs (SLiMs) predicted to mediate protein-protein interactions. Reanalysis of published transcriptomic data further suggested distinct downstream responses elicited by the intracellular domains of DSCAM and DSCAML1. Together, these findings suggest that post-duplication functional divergence of vertebrate DSCAM paralogs may have contributed to the evolution of molecular mechanisms underlying vertebrate neural development and circuit formation.

Evolutionary innovation is a key driver of the colonization of new environments and the adaptive radiations of major groups. Novel traits typically evolve through the modification of pre-existing characters but the genetic paths underlying their origin have been challenging to trace, and the general requirements for and relative order of different kinds of gene mutations have been difficult to assess. Here, we trace the genomic origins of four procoagulant venom toxins (factor X, factor V, group I phospholipase A2, and Kunitz-type toxins) that collectively underlie a novel, especially potent blood-clotting venom type in the recently evolved Australian brown snake and taipan clade. We discover evidence for a previously unknown fifth toxin, coagulation factor VII, and show that the toxins evolved through two distinct genetic paths. The factor X and factor V toxins evolved through the sequential de novo co-option of ancestral clotting factor proteins that entailed their heterotopic expression in the venom gland, the fixation of segmental duplications containing each locus, and subsequent gain-of-function mutations that rendered factor X and factor V constitutively active. In contrast, the phospholipase A2 and Kunitz-type toxins evolved by modifying the functions of neurotoxins that were part of the venom arsenal. Our findings support models in which innovative mutations in single-copy genes precede gene duplication in the evolution of novel proteins and offer a rare view into the genesis of a complex trait that has played a central role in a major adaptive radiation. Significance StatementThis study investigates how an entirely new blood-clotting venom type evolved during the recent radiation of Australias iconic venomous snakes. We traced the key genetic events that occurred on the evolutionary path to one of the worlds most potent venoms. We found that the novel venom activity evolved through the sequential co-option of multiple proteins of the snakes own blood-clotting system, followed by the modification of two venom neurotoxins into proteins with procoagulant activities. We suggest that these unique de novo gene co-options are seminal events that can unlock new ecological strategies, which in turn, may enable major adaptive radiations.

BackgroundSynonymous mutations, once considered neutral, can affect translation efficiency through mRNA folding and splicing, generating codon usage bias. This bias is often linked to genomic GC content, which also influences gene regulation. In the parasitoid wasp Lysiphlebus fabarum, GC content was previously shown to shift between developmental stages, with larvae showing higher GC than adults. Whether this phenomenon is widespread among insects remains unknown. ResultsTranscriptomic data from six insect species spanning Diptera, Hymenoptera, and Lepidoptera was used to compare GC content between expressed genes in larvae and adults. In five species, larval transcripts exhibited higher GC content than adult transcripts. Differential expression analysis revealed that stage-biased genes displayed consistent GC shifts, and orthologous gene families with representatives across species showed particularly GC-rich larval-biased genes in Hymenoptera and Diptera. At the genome scale, modeling in 317 insect species demonstrated an association between parasitic lifestyle and reduced mean GC content in Hymenoptera and Diptera, providing a possible ecological explanation for AT-rich genomes. ConclusionsOur results show that GC content is dynamic across developmental stages, independent of overall genome composition. Stage-specific GC enrichment may reflect adaptive codon usage optimizing translation during energetically demanding life-history stages such as larval development. Furthermore, the association between parasitism and reduced genomic GC highlights how ecological lifestyle might with genome content and evolution. Lastly, this work identifies candidate genes underlying stage-specific GC bias and provides new insights into the interplay between molecular evolution, development, and parasitic adaptation in insects.

Hearing in Lepidoptera mediates a range of ecologically important behaviours, including mate communication, predator avoidance, and acoustic signalling. In moths, the evolution of predator-prey interactions with bats has further shaped hearing through a sensory arms race, with repeated co-option of auditory organs to detect and evade echolocating predators. Despite significant prior characterization of the neurophysiology and behaviour of hearing in moths, the genetic basis of hearing is poorly understood in most insects. In this study, we identify a core set of putative auditory genes in Lepidoptera using a combination of homology-based searches from Drosophila and evolutionary rate analyses. We find 56 genes present across all species and investigate whether gene copy number varies among non-hearing and hearing lineages and among 3 different ear types. We discovered seven genes associated with ear type and one with ear presence, but did not find significant losses in gene copy number in non-hearing species. We identified three genes (btv, Dnai2, and nompB) with strong evidence of selection in hearing clades and five genes with weaker evidence of selection. We discuss the potential roles of btv, nompB, and Dnai2 in ciliary transport and the aging of hair cells, as well as the possibility of actively amplified hearing. Our study serves as a primer and resource for further gene mining and functional testing of auditory genes in moths and other insects.

Lysozyme has long been a model for understanding enzyme structure, function, and evolution. Early studies revealed a conflict between organismal phylogeny and the distribution of three functionally important amino acid residues in galliform birds. Lysozymes differing at all three amino acids appear functionally equivalent, but intermediates exhibit reduced stability and have not been observed in nature. However, the phylogeny suggests two independent occurrences of the three mutations, requiring two separate transitions through low fitness intermediates. We reexamined this apparent paradox using phylogenomic methods, accounting for incomplete lineage sorting and intralocus recombination. The lysozyme locus tree conflicts with an estimated species tree, but the conflict involves a short branch in coalescent units, consistent with incomplete lineage sorting. We also found evidence for recombination, with different parts of the lysozyme locus supporting alternative relationships. The three amino acids are encoded by exons located in different recombination-defined segments with different evolutionary histories. These results support a model where ancestral polymorphism, coupled with recombination between independently arising mutations, allowed rapid transitions between peaks in the fitness landscape without fixation of deleterious intermediates. Our findings resolve this long-standing question in lysozyme evolution and highlight the importance of considering complex genealogical processes such as incomplete lineage sorting and recombination when reconstructing ancestral proteins and interpreting apparent cases of molecular convergence.

Reconstructing the spatio-temporal history of human genetic lineages is fundamental to understanding human evolution and population distribution. While succinct tree sequences and maximum parsimony reconstruction methods applied to large-scale genomic data have improved our ability to trace the geographic history of genetic ancestry, they have essentially relied on Euclidean distances, which ineluctably ignore opportunity costs that have shaped human mobility patterns since the earliest human migrations and settlement formations. Here we propose an approach to incorporate realistic geographical migration costs through a human movement friction surface. Using simulated data mimicking the dispersal process of human migration out of Africa, we found that, compared to the Euclidean-based benchmark (M0), the proposed friction-based model (Mf) leads to a more accurate estimation of the geographical origin (n = 346, accuracy M0 = 0.18, f = 0.27) and genetic flux (n = 30, MSE M0 = 0.20, Mf = 0.12) through the Mandeb corridor in the Horn of Africa. We further illustrate these findings in a case study, in which our model seems to better identify plausible human migration paths from Eurasia to the Americas by accounting for geographic factors affecting migration opportunity costs, such as the Alaska Range and Rocky Mountains that represent physical barriers that constraint migration. While important migration drivers such as climate change, technological advances, social organization, and culture remain omitted here, our work highlights the importance of explicitly accounting for geographic constraints to improve our ability to reconstruct past human mobility and, ultimately, understand the evolution of human populations.

Immunoglobulin genes are a central component of jawed-vertebrate adaptive immunity. A previous study showed that the blunt-snouted clingfish Gouania willdenowi lacks immunoglobulin genes and T-cell receptor gamma/delta loci, while retaining T-cell receptor alpha/beta genes, MHC genes, and RAG1 /RAG2. Here I extend that observation to the family Gobiesocidae using all seven chromosome-level Gobiesocidae genome assemblies currently available. Manual tblastn and synteny-guided searches found no convincing immunoglobulin heavy-chain or light-chain loci in G. willdenowi, Gouania pigra, Gobiesox punctulatus, Apletodon dentatus, Lepadogaster candolii, Lepadogaster purpurea, or Diplecogaster bimaculata. Thus, the absence of antibody genes is best interpreted as a root-level character of clingfishes. The latest seven-species screen of 40 additional immune-associated genes shifts the broader interpretation in the same direction: the B-cell/adaptive core genes CD79A, CD79B, CIITA, TNFRSF13B, and TNFSF13B lack strong tblastn support in all sampled Gobiesocidae, and 37 of the 40 tested targets show an all-zero binary pattern at the presence threshold. Only IL21R.1, TYROBP, and TNFRSF11A show strong hits in one or more species. I therefore interpret the principal immune-gene erosion as occurring at or near the Gobiesocidae root rather than as a recent Gouania-specific process, while keeping weak, paralog-sensitive, and patchy loci provisional. RAG2 comparisons show a shared Gobiesocidae PHD-domain C-to-S replacement in the zinc-binding motif, with apparently intact RAG2 coding sequence. A family-wide TRG/TRD screen did not recover TRGV V segments or accepted TRDC constant-region exons, but it did detect TRGC-like constant exons in several genomes. These TRGC-like sequences are probably not canonical TRG constant exons without further validation, so I treat the gamma/delta system as eroded or rearranged rather than as a complete root-level loss equivalent to the Ig loss. The RAG2 variant provides a plausible molecular context for antigen-receptor remodeling, but it is not evidence that RAG genes are pseudogenized, because TCR alpha/beta, MHC genes, and RAG1 /RAG2 are retained. Gobiesocidae are therefore best described as a vertebrate family with ancestral loss of canonical immunoglobulin genes and associated root-level erosion of B-cell and immune-related genes, not as a lineage lacking adaptive immunity in its entirety. HighlightsO_LISeven chromosome-level Gobiesocidae genomes lack convincing canonical IgH and IgL loci. C_LIO_LIThe strongest non-Ig losses map to the B-cell/adaptive core: CD79A, CD79B, CIITA, TNFRSF13B, and TNFSF13B. C_LIO_LITCR alpha/beta, MHC genes, and RAG1 /RAG2 are retained, so Gobiesocidae should not be described as lacking adaptive immunity in full. C_LIO_LIA shared Gobiesocidae RAG2 PHD-domain C-to-S variant provides candidate molecular context for antigen-receptor remodeling. C_LI

Mutations are often thought to destabilize protein structures. However, many proteins are naturally unstructured and the effect of mutations on such proteins especially in the absence of selection, remains unclear. Here, we develop a computational model to study the effects of mutations on structural disorder in both random and natural sequences, including those derived from evolutionary conserved proteins, and evolutionarily novel de novo proteins. We find that while structured proteins tend to lose structure, unstructured proteins exhibit the opposite trend, becoming more structured in the absence of directional selection. This bidirectional dynamics is robust to mutation biases, genetic code structure, and sequence origin, suggesting that it arises from the topology of the sequence-structure landscape rather than intrinsic directional mechanisms. Our results are consistent with a diffuse landscape in which structured and disordered sequences are interspersed throughout sequence space. These findings suggest that neutral evolution can result in structure formation and may facilitate the early structural evolution of de novo proteins prior to strong selection.

Fossil data is crucial to construct phylogenetic time trees, which serve as the basis to test a wide range of evolutionary hypotheses. While the fossil record is known to be incomplete, modern stratigraphy provides predictions of the structure of the fossil record as expressed by gap location and duration. Advances in phylogenetic model development allow us to propagate this information into Bayesian phylogenetic inference in the form of priors on time-variable fossil sampling. However, the impact and role of stratigraphic architectures on time tree inference has so far remained unexplored. We introduce a novel simulation framework that combines realistic stratigraphic forward models with phylogenetic simulations. Using this framework, we examine (1) how stratigraphically plausible model violations of fossil sampling due to gaps affect total-evidence inference under the fossilized birth-death model and (2) if stratigraphic knowledge on gap duration and timing improves inference when incorporated in priors on fossil sampling. We find that total-evidence analysis is robust to stratigraphically plausible distribution of gaps in disparate stratigraphic architectures, with results being instead dominated by the number of morphological characters. Surprisingly, incorporating information on prominent gaps in the stratigraphic record does not improve phylogenetic inference. Our results suggest that phylogenetic inference is robust to model violations introduced by stratigraphic gaps over short timescales, with results being dominated by a priori known data availability constraints such as morphological character matrix size. This research establishes the foundations for joint modeling of phylogenetic and stratigraphic processes and narrows the knowledge gap between paleontology, stratigraphy, and neontology.

Limb loss in vertebrate animals is surprisingly common despite imposing strong functional constraints. These pressures funnel species towards regions of limited ecological and phenotypic space. To date, snakes have been considered unique in having escaped this pattern. Using a new species-level phylogeny and comparative morphological and dietary datasets, we show that pygopods, a group of limbless Australo-Papuan geckos, have undergone a similar evolutionary trajectory to snakes. Our analyses provide evidence of exceptional morphological and diet evolution. This is exemplified by strong niche partitioning among genera through dietary specialization and greater than expected dietary disparity. Diversification in pygopods has also been driven by extreme phenotypic evolution, with pygopods encompassing much of the morphological space covered by all other limb-reduced lizards. Interestingly, the diversification of pygopods has resulted in only a modest number of species, emphasizing the decoupling of diversity and richness possible in adaptive radiations.

Mitochondrial loci were for long considered as markers of choice to reconstruct phylogenies. The development of high-throughput sequencing over the past two decades fostered the sequencing of mitogenomes, allowing further macroevolutionary questions to be tested. Several biological traits of birds (e.g. body mass, migration distances) have been related to mitochondrial substitution rates. Environmental parameters in ectothermics vertebrates, and potentially in endotherms, have been further suggested to impact substitution rates for specific taxa or loci. Yet, the relative importance of biological traits versus bioclimatic variables is unknown because the former were not systematically controlled for in studies that underlined the effect of the bioclimatic variables. To assess the importance of bioclimatic variables on selection regimes, we analysed the thirteen mitochondrial protein-coding genes for 176 Piciformes (toucans, honeyguides, woodpeckers), a clade with homogeneous life-history traits that can be found in diverse bioclimatic environments. Our analyses highlighted a negative relationship between temperature annual range and the non synonymous to synonymous substitutions ratio. The higher purifying selection in temperate environments may be a result of the strong constraints on maintaining an optimal metabolism in broader climatic variations. Our results further highlight that care should be taken when applying general mitochondrial clocks to estimate divergence times among avian lineages distributed in different climatic conditions.