Molecular biology and evolution最新文献

Recombination suppression often evolves around sex-determining loci and extends stepwise, resulting in adjacent regions with different levels of divergence between sex chromosomes, called evolutionary strata. In Ascomycota fungi, evolutionary strata around the mating-type (MAT) locus have been reported only in pseudo-homothallic species, which have a diploid-like life cycle with mycelia carrying nuclei of both mating types. In contrast, no recombination suppression has been observed in heterothallic fungi, where colonies contain only a single mating type. Here, we investigated the evolution of recombination suppression in a clade of dung fungi encompassing 16 pseudo-homothallic and three heterothallic sibling species from the Schizothecium genus (Ascomycota, Sordariales). The analysis of genetic divergence based on genome sequencing indicated recombination suppression around the MAT locus in all 13 pseudo-homothallic species examined. The nonrecombining region ranged from 600 kb to 1.6 Mb and harbored multiple evolutionary strata, varying in size and number among species. The clustering of alleles according to mating type in gene genealogies, the high linkage disequilibrium, and an inversion in one species supported the lack of recombination in the MAT-proximal region in pseudo-homothallic species. The overall lack of trans-specific polymorphism suggested multiple independent recombination suppression events or occasional recombination/genic conversion. In heterothallic species, progeny analyses showed that recombination occurs in regions at physical distances from the MAT locus similar to those in which it is lacking in the pseudo-homothallic species. We thus revealed here multiple, likely independent evolutionary strata, associated with an extended diploid-like stage in Schizothecium fungi.

Molecular convergence, where specific nonsynonymous changes in protein-coding genes lead to identical amino acid substitutions across multiple lineages, provides strong evidence of adaptive evolution. Detecting this signal across diverse taxa can reveal adaptive variation that may not be apparent when studying individual lineages. In this study, we search for convergent substitutions in the most speciose group of vertebrates, teleost fishes. Using an unsupervised approach, we detected convergence in 89 protein-coding gene families across 143 chromosomal-level genomes. To assess their functional implications, we integrate data on protein properties, gene expression across species and tissues, single-cell RNA sequencing of zebrafish embryonic development, and gene perturbation experiments in zebrafish. We found that, on average, the convergent genes had more gene copies as compared to background sets of genes. The convergent genes were associated with diverse processes including embryonic development, tissue morphogenesis, metabolism, and heat stress response. We found evidence that convergent substitutions were more radical than nonconvergent substitutions. When analyzing the expression of the convergent genes, we found that only one-third of them were tissue-specific, while the majority were expressed across multiple tissues and cell types. Genetic perturbation data further showed that the convergent genes can affect multiple structures across diverse tissues. These results highlight the important functional roles of the convergent genes, their potential pleiotropic nature, and suggest that they may underlie the evolution of lineage-specific adaptations in teleost fishes.

The insulin and insulin-like growth factor (IGF) system regulates essential biological functions such as growth, metabolism, and development. While its physiological roles are well characterized, the evolutionary origins and molecular diversification of its ligands and receptors remain incompletely defined. Here, we present the most comprehensive phylogenetic and sequence conservation analysis of this system to date, using over 1,000 sequences from vertebrates, invertebrates, and viruses. Our analyses reveal that insulin, IGF-1, and IGF-2 form distinct monophyletic clades that diverged after the emergence of vertebrates, with IGF-1 being the most conserved ligand. We show that IGF1R-binding residues, especially in the A- and B-domains of IGF-1, are highly conserved across vertebrates, while insulin's Site 2 residues, which overlap with its dimerization and hexamerization surface, are more variable-correlating with the loss of hexamer formation in hystricomorphs, reptiles, and jawless fish. Unexpectedly, we identify a 12-amino acid insert in the insulin receptor (IR) of turtles and tortoises, previously thought to be unique to mammalian IR-B isoform, challenging the view that receptor isoform diversity is a mammalian innovation. We also show that marsupials and monotremes retain ancestral receptor domain features shared with reptiles and birds and that avian insulins, particularly A-chain residues, are unusually conserved. Viral insulin/IGF-like peptides fall into two distinct clades that resemble either IGFs or insulin. Together, these findings illuminate the evolutionary architecture of the insulin/IGF system, highlight unexpected lineage-specific adaptations, and provide a framework for understanding hormone-receptor function across biology and therapeutic design.

MicrobeTrace is a free, secure, browser-based bioinformatics tool to integrate and visualize epidemiologic, laboratory, and molecular data for outbreak investigations, with over 14,000 users from 127 countries. Regular testing, user feedback, and comparison with other bioinformatics tools identified areas for improvement, prompting major architectural and functional upgrades. In MicrobeTrace 2.0, we refactored the codebase using Angular to improve scalability, performance, and usability. We also replaced the D3.js visualization engine with Cytoscape.js for faster, more efficient rendering of large networks. The update adds enhanced visualizations, new analytical tools, and expanded functionality within existing views. It also supports seamless integration with external phylogenetic platforms, such as Nextstrain and UShER (Ultrafast Sample Placement on Existing Trees), enabling users to import phylogenetic trees, visualize them as genetic networks, and securely enrich them with epidemiological and demographic metadata. These enhancements position MicrobeTrace as a next-generation, interoperable tool for genomic epidemiology and data-driven public health response.

The Central Plain of China, the cradle of Chinese civilization, experienced major demographic upheavals during the Qing era (1644-1912 AD), yet its population's genetic history during this critical period remains largely uncharacterized. Here, we generated genome-wide data for 46 Qing Dynasty individuals from the Sanzhiyuan cemetery in Sanmenxia, Henan province. The Sanzhiyuan population exhibits remarkable genetic homogeneity and shows substantial genetic continuity with preceding populations of the Yellow River region dating back to the Late Neolithic. We successfully model them as direct descendants of Tang Dynasty populations. Notably, despite the Qing being ruled by the ethnically distinct Manchu elite, we detected no evidence of large-scale genetic admixture with Manchu, Mongol, or other northern or West Eurasian groups. Furthermore, we demonstrate that these Qing-era individuals are direct ancestors of the modern Han population in Henan, completing an unbroken multi-millennial genetic lineage. Our findings further demonstrate the stability of the genetic profile of the Central Plains population-a stability that has persisted for millennia and remained profoundly unaffected by major historical upheaval.

Endogenous retroviral envelope (ERV env) genes, notably syncytins, are known for driving placental development in mammals and lizards. However, their broader contributions to non-mammalian vertebrates, particularly viviparous fish, remain largely unexplored. Here, we present the discovery and functional characterization of three co-opted/captured ERV env gene clades, including a Percom-env clade comprising previously reported percomORF in the viviparous teleost Sebastes schlegelii. Our findings reveal that each gene clade plays a distinct and critical role in neural regulation, reproductive maturation, and viviparity. Notably, Percom-env percomORF retains fusogenic activity and its brain-specific expression is driven by conserved regulatory elements across Percomorpha. Meanwhile, Seb-env4 env genes, expressed uniquely in the testis, support seasonal gonadal maturation and Sertoli cell maintenance. Lastly, Seb-env3 env genes, localized at the maternofetal interface, retain a robust fusion capacity essential for follicular placentation, and have persisted for approximately 15 million years in the Sebastes genus, thus identified as candidate syncytin-Seb, likely underpinning the emergence of viviparity. These findings demonstrate env co-option/capture drives teleost adaptations, extending retroviral env-mediated placentation beyond mammals and lizards, and highlight conserved mechanisms in vertebrate reproductive evolution.

Evolutionary simulations of multiple chromosomes, even up to the scale of full-genome simulations, are becoming increasingly important in population genetics and evolutionary ecology. Unfortunately, the popular simulation framework SLiM has always been intrinsically limited to simulations of a single diploid chromosome. Modeling multiple chromosomes of different types, such as sex chromosomes, has always been cumbersome, even with scripting, presenting a substantial barrier to the development of full-genome simulations. Here we present SLiM 5, a major extension of SLiM's capabilities for simulating multiple chromosomes. Modeling up to 256 chromosomes is now possible, and each chromosome may belong to any of a wide variety of types-not just autosomes (diploid and haploid), but also sex chromosomes (X, Y, Z, and W), haploid mitochondrial and chloroplast DNA, and more. This new functionality is integrated across all of SLiM, including not only the mechanics of reproduction and inheritance, but also input and output of multi-chromosome data in formats like VCF, and tree-sequence recording across multiple chromosomes. New recipes in the SLiM manual demonstrate these new features, and SLiM's graphical modeling environment, SLiMgui, has been extended in many ways for the visualization of multi-chromosome models. These new features will open new horizons and enable a heightened level of realism for full-genome simulations.

Our understanding of the vertebrate immune system is dominated by a few model organisms such as mice. This use of a few model systems is reasonable if major features of the immune systems evolve slowly and are conserved across most vertebrates, but may be problematic if there is substantial macroevolutionary change in immune responses. Here, we present a test of the macroevolutionary stability, across 14 species of ray-finned fishes, of the transcriptomic response to a standardized immune challenge. Intraperitoneal injection of an immune adjuvant (alum) induces a fibrosis response in nearly all jawed fishes, which in some species contributes to anti-helminth protection. Despite this conserved phenotypic response, the underlying transcriptomic response is highly inconsistent across species. Although many gene orthogroups exhibit differential expression between saline versus alum-injected fish in at least one species, few orthogroups exhibit consistent differential expression across species. This result suggests that although the phenotypic response to alum (fibrosis) is highly conserved, the underlying gene regulatory architecture is very flexible and cannot readily be extrapolated from any one species to fishes (or vertebrates) more broadly. The vertebrate immune response is remarkably changeable over macroevolutionary time, requiring a diversity of model organisms to describe effectively.

The growing availability of genomes from non-model organisms offers new opportunities to identify functional loci underlying trait variation through comparative genomics. While cis-regulatory regions drive much of phenotypic evolution, linking them to specific functions remains challenging. We identified 514 cis-regulatory motifs enriched in regulatory regions of five diverse grass species, with 73% consistently enriched across all, suggesting a deeply conserved regulatory code. Leveraging 57 new contig-level genome assemblies, we then quantified shared occupancy of specific motif instances within gene-proximal regions across 589 grass species, revealing widespread gain and loss over evolutionary time. Shared occupancy declined rapidly over the first few million years of divergence, yet ∼50% of motif instances were shared back to the origin of grasses ∼100 million years ago. We used phylogenetic mixed models to identify motif gains and losses associated with ecological niche transitions. Our models revealed significant environmental associations across 1282 motif-orthogroup combinations, including convergent gains of HSF/GARP motifs at an alpha-N-acetylglucosaminidase gene associated with occurrence in temperate environments. Our findings support a "stable motifs, variable binding sites" model in which cis-regulatory evolution involves turnover of thousands of individual binding site instances while largely preserving transcription factors' binding preferences. Our results highlight the potential of comparative genomics and phylogenetic mixed models to reveal the genetic basis of complex traits.