Molecular biology and evolution最新文献

Due to their remarkable diversity and rapid evolution, conotoxins-peptide toxins from predatory marine cone snails-provide a powerful system for exploring how gene diversification may contribute to the development of lineage-specific adaptations. We previously demonstrated that 2-loop Tau conotoxins represent an evolutionary innovation associated with mollusk-hunting behaviors in cone snails. Here, we investigate the evolutionary history of these toxins as a model to understand the mechanism of ancestral gene neofunctionalization, which may have contributed to the emergence of mollusk-hunting in cone snails. Using ancestral sequence reconstruction, we present a model in which ancestral T-superfamily conotoxins neofunctionalized into the 2-loop Tau conotoxins. Predicted ancestral sequences reveal an intermediate structure between the classic T-superfamily conotoxins and the derived 2-loop Tau forms. Notably, these ancestral intermediates acquired a new cysteine scaffold that facilitated a structural transition from a globular to a ribbon fold. This conformational shift was followed by sequence-level changes that presumably enhanced activity against molecular targets in mollusks. We propose that the emergence of 2-loop Tau conotoxins may have been one factor that contributed to the emergence of molluscivory, providing insight into how gene innovation may underlie ecological diversification.

Shared fusions between ancestral chromosomal linkage groups have previously been used to support phylogenetic groupings, notably sponges with cnidarians and bilaterians to the exclusion of ctenophores, rendering ctenophores the sister group to all other animals. The linkage groups used to identify these fusions were assessed for statistical significance relative to a model of randomly shuffled genes. I argue that the method of random shuffling treated all species as equally distant from each other and so overestimated the significance of the observed linkages. I calculate alternative statistics and further argue that there are likely to be real linkage groups that are not identified as significant. If linkage groups are not supported statistically, they cannot reliably be used to identify shared derived chromosomal rearrangements, and hence phylogenetic hypotheses derived from them are suspect.

Whole-genome duplication (WGD), a widespread macromutation across eukaryotes, is predicted to affect the tempo and modes of evolutionary processes. By theory, the additional set(s) of chromosomes present in polyploid organisms may reduce the efficiency of selection while, simultaneously, increasing heterozygosity and buffering deleterious mutations. Despite the theoretical significance of WGD, empirical genomic evidence from natural polyploid populations is scarce and direct comparisons of selection footprints between autopolyploids and closely related diploids remains completely unexplored. We therefore combined locally sampled soil data with resequenced genomes of 76 populations of diploid-autotetraploid Arabidopsis arenosa and tested whether the genomic signatures of adaptation to distinct siliceous and calcareous soils differ between the ploidies. Leveraging multiple independent transitions between these soil types in each ploidy, we identified a set of genes associated with ion transport and homeostasis that were repeatedly selected for across the species' range. Notably, polyploid populations have consistently retained greater variation at candidate loci compared with diploids, reflecting lower fixation rates. In tetraploids, positive selection predominantly acts on such a large pool of standing genetic variation, rather than targeting de novo mutations. Finally, selection in tetraploids targets genes that are more central within the protein-protein interaction network, potentially impacting a greater number of downstream fitness-related traits. In conclusion, both ploidies thrive across a broad gradient of substrate conditions, but WGD fundamentally alters the ploidies adaptive strategies: tetraploids leverage their greater genetic variation and redundancy to compensate for the predicted constraints on the efficacy of positive selection.

Bayesian phylodynamic models have become essential for reconstructing population history from genetic data, yet their accuracy depends crucially on choosing appropriate demographic models. To address uncertainty in model choice, we introduce a Bayesian model averaging (BMA) framework that integrates multiple parametric coalescent models-including constant, exponential, logistic, and Gompertz growth-along with their "expansion" variants that account for non-zero ancestral populations. Implemented in a Bayesian setting with Metropolis-coupled Markov chain Monte Carlo, this approach allows the sampler to switch among candidate growth functions, thereby capturing demographic histories without having to pre-specify a single model. Simulation studies verify that the logistic and Gompertz models may require specialized sampling strategies such as adaptive multivariate proposals to achieve robust mixing. We demonstrate the performance of these models on datasets simulated under different substitution models, and show that joint inference of genealogy and population parameters is well-calibrated when properly incorporating correlated-move operators and BMA. We then apply this method to two real-world datasets. Analysis of Egyptian Hepatitis C virus sequences indicates that models with a founder population followed by a rapid expansion are well supported, with a slight preference for Gompertz-like expansions. Our analysis of a metastatic colorectal cancer single-cell dataset suggests that exponential-like growth is plausible even for an advanced stage cancer patient. We believe this highlights that tumor subclones may retain substantial proliferative capacity into the later stages of the disease. Overall, our unified BMA framework reduces the need for restrictive model selection procedures and can also provide deeper biological insights into epidemic spread and tumor evolution. By systematically integrating multiple growth hypotheses within a standard Bayesian setting, this approach naturally avoids overfitting and offers a powerful tool for inferring population histories across diverse biological domains.

Some of the most striking examples of phenotypic variation within species are controlled by supergenes. However, most research on supergenes has focused on their emergence and long-term maintenance, leaving the later stages of their life cycle largely unexplored. Specifically, what happens to a derived supergene haplotype when the trait it controls reaches fixation? Here we answer this question using the ancient supergene system of Formica ants, where (monogynous) single-queen colonies typically carry only the ancestral haplotype M while the derived haplotype P is exclusive to (polygynous) colonies with multiple queens. Through comparative population genomics of 264 individuals from all seven European wood ant species, we found that the P haplotype was present in only 1/3 obligately polygynous species (Formica polyctena). In the two others (Formica aquilonia and Formica paralugubris), the P haplotype was completely missing except for duplicated P-specific paralogs of two genes, Zasp52 and TTLL2, with Zasp52 being directly involved in wing muscle development. We hypothesize that these genes play a direct role in polygyny and contribute to differences in body size and/or dispersal behavior between monogynous and polygynous queens. A complete lack of P/P genotypes among the 261 workers suggests strong selection against such genotypes. While our analyses did not reveal evidence of increased mutation load on the P, it is possible that this skew in genotype distributions is driven by a few loci with strong fitness effects. We propose that selection to escape P-associated fitness costs underlies the loss of this haplotype in obligately polygynous wood ants.

Some genes encoding proteins within the co-evolved pre- and postsynaptic compartments are present in genomes long preceding the origination of the synapse within the animal kingdom. DLG4, gene encoding PSD-95, is one of the most abundant synaptic proteins. It is a MAGUK family member that shares a conserved domain structure comprised of one or multiple PDZ domains, a Src homology 3 (SH3), and a guanylate kinase (GK) domain. Here, we construct the phylogeny of the tri-PDZ domains in DLG4 to its deep ancestral origin in Filozoa, which includes animals and their nearest unicellular relatives. PDZ domain architecture appears to be a strong organizing feature of this gene lineage that originated with a single ancestral PDZ3-like domain in Capsaspora owczarzaki from which PDZ1 and PDZ2 were derived. The strong conservation of individual PDZ domain identities was captured by Evolutionary Scale Modeling (ESM2) across the boundary to the animal kingdom, corroborating distinct clades formed by the divergence of PDZ1, PDZ2, and PDZ3 in the phylogeny. CRIPT, PDZ3 ligand, is present in all Filozoa genomes studied here. AlphaFold2 Multimer demonstrates conserved binding function; however, conserved binding does not completely depend on either sequence motifs or hydrophobicity profiles. Rather, the most conserved feature is hydrogen bonds at the 0 and -2 positions of the ligand as an ancient foundational innovation for PDZ3 ligand interaction. Hydrogen bonds may loosen the sequence requirements for binding to allow a more extensive search space for protein-protein interactions that enhance fitness before the mutations that secure those interactions occur.

Parasitic lifestyles often impose profound evolutionary pressures, affecting molecular evolution through both adaptive and non-adaptive mechanisms. Among barnacles (subclass Cirripedia), the obligate parasitic Rhizocephala differ markedly from their filter-feeding thoracican relatives in morphology, ecology, and life history. However, how the shift to parasitism has shaped mitochondrial genome evolution within Cirripedia remains unclear. Here, we present the first comprehensive comparative analysis of mitochondrial genomes between parasitic and non-parasitic barnacles, including three newly sequenced and one unpublished species of parasitic Rhizocephala, a clade whose mitochondrial genomes had not been characterized until now. Phylogenomic and molecular evolutionary analyses reveal that Rhizocephala species exhibit extremely long branches likely attributed to the clade-specific tempo (high substitution rate) and mode (selection pressure) of mtDNA sequence evolution associated with their parasitic lifestyle. A two-cluster molecular clock test reveals significantly elevated substitution rates across rhizocephalans, consistent with reduced effective population sizes (Ne) linked to their opportunistic, host-dependent life cycles. We also detect signatures of positive selection in protein-coding genes encoding key components of the electron transport chain complexes III and IV. Structural modeling highlights amino acid substitutions at functionally critical sites for electron transfer and proton pumping, suggesting adaptive modifications to mitochondrial bioenergetics under hypoxic conditions within host tissues. Together, our findings underscore that both non-adaptive (genetic drift, relaxed selection) and adaptive (positive selection) processes have driven the rapid sequence divergence of mitochondrial genomes in parasitic Rhizocephala. Further experimental study is needed to elucidate how mitochondrial and nuclear-encoded subunits of oxidative phosphorylation coevolve in this specialized parasitic group.

Ultraconserved elements are segments of DNA that are identical or nearly identical in distantly related species. Finding 100% identity over long evolutionary times is unexpected, but pioneering research in human-mouse pairwise alignment uncovered something even more puzzling: these elements are not as rare as previously suspected. Furthermore, their sizes are distributed as a power-law, a feature that cannot be explained by standard models of genome evolution where conservation is expected to decay exponentially. Despite the power-law behavior having been reported and investigated in a wide variety of biological and physical contexts, from cell-division to protein family evolution, why it appears in the size distribution of ultraconserved elements remains elusive. To address this question, I propose a model of DNA sequence evolution by mutations of arbitrary length based on a classical integro-differential equation that arises in various applications in biology. The model captures the ultraconserved size distribution observed in pairwise alignments between human and 40 other vertebrates, encompassing more than 400 million years of evolution, from chimpanzee to zebrafish. I also show that the model can be used to predict other important aspects of genome evolution, such as indel rates and conservation in functional classes.