Molecular biology and evolution最新文献

Selection is a fundamental evolutionary force that shapes patterns of genetic variation across species. However, simulations incorporating realistic selection along heterogeneous genomes in complex demographic histories are challenging, limiting our ability to benchmark statistical methods aimed at detecting selection and to explore theoretical predictions. stdpopsim is a community-maintained simulation library that already provides an extensive catalog of species-specific population genetic models. Here, we present a major extension to the stdpopsim framework that enables simulation of various modes of selection, including background selection, selective sweeps, and arbitrary distributions of fitness effects (DFE) acting on annotated subsets of the genome (for instance, exons). This extension maintains stdpopsim's core principles of reproducibility and accessibility while adding support for species-specific genomic annotations and published DFE estimates. We demonstrate the utility of this framework by comparing methods for demographic inference, DFE estimation, and selective sweep detection across several species and scenarios. Our results demonstrate the robustness of demographic inference methods to selection on linked sites, reveal the sensitivity of DFE-inference methods to model assumptions, and show how genomic features, like recombination rate and functional sequence density, influence power to detect selective sweeps. This extension to stdpopsim provides a powerful new resource for the population genetics community to explore the interplay between selection and other evolutionary forces in a reproducible, user-friendly framework.

Mechanisms of X chromosome dosage compensation have been studied in model organisms with distinct sex chromosome ancestry. However, the diversity of mechanisms as a function of sex chromosome evolution is largely unknown. Here, we anchor ourselves to the nematode Caenorhabditis elegans, where dosage compensation is accomplished by an X chromosome-specific condensin that belongs to the family of structural maintenance of chromosomes (SMC) complexes. By combining a phylogenetic analyses of the C. elegans dosage compensation complex with a comparative analysis of its epigenetic signatures, such as X-specific topologically associating domains and enrichment of H4K20me1, we show that the condensin-mediated mechanism evolved recently in the lineage leading to Caenorhabditis following an SMC-4 duplication. Unexpectedly, we found an independent duplication of SMC-4 in Pristionchus pacificus along with X-specific topologically associating domains and H4K20me1 enrichment, which suggests that condensin-mediated dosage compensation evolved more than once in nematodes. Differential expression analysis between sexes in several nematode species indicates that dosage compensation itself precedes the evolution of X-specific condensins. In Rhabditina, X-specific condensins may have evolved in the presence of an existing mechanism linked to H4K20 methylation as Oscheius tipulae X chromosomes are enriched for H4K20me1 without SMC-4 duplication or topologically associating domains. In contrast, Steinernema hermaphroditum lacks H4K20me1 enrichment, SMC-4 duplication, and topologically associating domains. Together, our results indicate that dosage compensation mechanisms continue to evolve in species with shared X chromosome ancestry, and SMC complexes may have been co-opted at least twice in nematodes, suggesting that the process of evolving chromosome-wide gene regulatory mechanisms are constrained.

Trichomonas species are a diverse group of microbial eukaryotes (also commonly referred to as protists) that are obligate extracellular symbionts associated with or attributed to various inflammatory diseases. They colonize mucosal surfaces across a wide range of hosts, all of which harbor a resident microbiota. Their evolutionary history likely involved multiple host transfers, including zoonotic events from columbiform birds to mammals. Using comparative transcriptomics, this study examines Trichomonas gallinae co-cultured with Escherichia coli, identifying a molecular toolkit that Trichomonas species may use to interact with bacterial members of the microbiota. Integrating transcriptomic data with comparative genomics and phylogenetics revealed a conserved repertoire of protein-coding genes likely acquired through multiple lateral gene transfers (LGTs) in a columbiform-infecting ancestor. These LGT-derived genes encode muramidases, glucosaminidases, and antimicrobial peptides-enzymes and effectors capable of targeting bacterial cell walls, potentially affecting the bacterial-microbiota composition across both avian and mammalian hosts. This molecular toolkit suggests that Trichomonas species can actively compete with and exploit their surrounding microbiota for nutrients, potentially contributing to dysbiosis associated with Trichomonas infections. Their ability to target bacterial populations at mucosal surfaces provides insight into how Trichomonas species may have adapted to diverse hosts and how they could influence inflammatory mucosal diseases in birds and mammals.

Transposable elements (TEs) are abundant selfish genetic elements that can mobilize in their host genome, causing DNA damage, mutations, and chromosome rearrangements. TE silencing is thus critical, and is initiated by maternally loaded piRNAs, leading to their repression. Consistently, paternally inherited TEs are derepressed in the progeny of Drosophila crosses involving a naive female. TEs have also been found to be derepressed in interspecific crosses, which is proposed to result from suboptimal interactions of piRNA pathway proteins. Fundulus heteroclitus and F. diaphanus hybridize in nature and produce viable and fertile offspring that sometimes reproduce asexually. We characterized the repetitive DNA content of these species and their asexually reproducing hybrids. TE load was slightly higher than expected in hybrids and associated with younger repeats. Two biparentally inherited active Neptune subfamilies showed a remarkable ∼3- to 4-fold accumulation in hybrids. These results are consistent with suboptimal piRNA pathway function, leading to active TE accumulation.

Plasmids are important drivers of evolutionary transformations and ecological adaptation in prokaryotes. Plasmids supplying the host with beneficial functions may become domesticated and gain a stable inheritance within the host lineage. Domesticated plasmids may comprise core genes that are present in all taxon members. The origin of plasmid core genes remains poorly understood and alternative scenarios entailing gene translocation or genetic redundancy are debated. Studying plasmid evolution in the plant-associated Pantoea, we show that the large Pantoea plasmids (LPP-1 and LPP-2) are domesticated. We infer that the LPP-1 was acquired in the ancestor of plant-associated Pantoea species. The LPP-2 acquisition is traced to the ancestor of plant growth-promoting species. We show that both plasmids are vertically inherited and the LPP-1 replication is furthermore coordinated with chromosome replication. Both plasmids harbor core gene families at the genus (LPP-1) or species (LPP-2) level. Using phylogenomics we infer a deep divergence between plasmid and chromosomal core genes, indicating rare gene translocation between the replicons. Our results suggest that the LPP-1 and LPP-2 acquisition introduced genetic redundancy with chromosomal genes, that was followed by successive waves of differential gene loss. The domestication of both plasmids likely contributed to species divergence in Pantoea.

Mutator phenotypes are short-lived due to the rapid accumulation of deleterious mutations. Yet, recent observations reveal that certain fungi can undergo prolonged accelerated evolution after losing genes involved in DNA repair. Here, we surveyed 1,154 yeast genomes representing nearly all known yeast species of the subphylum Saccharomycotina (phylum Ascomycota) to examine the relationship between reduced gene repertoires broadly associated with genome stability functions (eg DNA repair, cell cycle) and elevated evolutionary rates. We identified 3 distantly related lineages-encompassing 12% of species-that had both the most streamlined sets of genes involved in genome stability (specifically DNA repair) and the highest evolutionary rates in the entire subphylum. Two of these "faster-evolving lineages" (FELs)-a subclade within the order Pichiales and the Wickerhamiella/Starmerella (W/S) clade (order Dipodascales)-are described here for the first time, while the third corresponds to a previously documented Hanseniaspora FEL. Examination of genome stability gene repertoires revealed a set of genes predominantly absent in these 3 FELs, suggesting a potential role in the observed acceleration of evolutionary rates. In the W/S clade, genomic signatures are consistent with a substantial mutational burden, including pronounced A|T bias and endogenous DNA damage. Interestingly, we found that the W/S clade also contains DNA repair genes possibly acquired through horizontal gene transfer, including a photolyase of bacterial origin. These findings highlight how hypermutators can persist across macroevolutionary timescales, potentially linked to the loss of genes related to genome stability, with horizontal gene transfer as a possible avenue for partial functional compensation.

Many Mycobacterium tuberculosis genome sites experience different selective forces depending on whether a patient is treated with antibiotics. Here, we searched for pairs of such sites that evolve interdependently. We reconstructed the phylogeny of more than 11,000 Mycobacterium tuberculosis clinical isolates with known phenotypes for at least one of the 13 antitubercular drugs. By analyzing the distributions of substitutions and phenotypic state changes on the phylogeny, we identified sites where substitutions were associated with the acquisition of drug resistance or occurred preferentially in resistant or susceptible lineages. Among these sites, we searched for concordantly and discordantly evolving site pairs, carefully accounting for the presence of drug-associated selection and other coordinated selective forces. We identified one concordantly evolving site pair and 14 discordantly evolving site pairs between sites that are known to be strongly associated with resistance to antitubercular drugs. The concordantly evolving site pair and five out of 14 discordantly evolving site pairs were between sites whose substitutions were associated with resistance to different drugs, while the other nine discordantly evolving site pairs were between sites located either in the same genes or in different genes involved in alternative adaptive pathways to the same drugs. Overall, our findings emphasize the dual role of epistasis, which can both promote and limit the acquisition of resistance to multiple drugs.

Haplotype-based statistics are widely used for finding genomic regions under positive selection. At the heart of many such statistics is the computation of extended haplotype homozygosity (EHH), which captures the decay of homozygosity away from a focal site. This computation, repeated for potentially millions of sites, is computationally demanding, as it involves tracking counts of unique haplotypes iteratively over long genomic distances and across many individuals. Because of these computational challenges, existing tools do not scale well when applied to large-scale population datasets, such as the 1,000 Genomes Project, or the UK Biobank with 500,000 individuals. Optimizing computation becomes crucial when data sets grow large, especially when handling large sample sizes or generating training data for machine learning algorithms. Here, we propose a dynamic programming algorithm that substantially improves runtime and memory usage over existing tools on both real and simulated data. On real phased data, we achieve 5-50x speedup with minimal memory footprint. Our simulations show an even more pronounced performance gap with large populations (up to 15x speedup and 46x memory reduction). EHH-based statistics designed for unphased genotypes run an order of magnitude faster, and multi-parameter support results in 20x runtime improvement. Source code and binaries are available at https://github.com/szpiech/selscan as selscan v2.1.

Ribosomes are essential for protein synthesis and require ribosome biogenesis factors for assembly. To uncover the evolutionary diversity of ribosome biogenesis, we analyzed over 30,000 bacterial genomes and revealed that Candidate Phyla Radiation, also known as the phylum Patescibacteria, characterized by reduced genomes and smaller ribosomes, has about half the average number of ribosome biogenesis factors compared with non-Candidate Phyla Radiation bacteria. Notably, key ribosome biogenesis factors such as der, obgE, and rbfA, considered indispensable, are conserved in only around 20%-70% of Candidate Phyla Radiation genomes. Since such repertoires were not observed in reduced genomes of other phyla, Candidate Phyla Radiation presumably diverged early in bacterial evolution. We further confirmed that ribosomal structural changes correlate with reduced ribosome biogenesis factor, evidencing co-evolution between ribosome biogenesis factor and the ribosome. These findings suggest that ribosomal biogenesis is more flexible than recognized, and the small cell and genome sizes of Candidate Phyla Radiation bacteria and their early divergence may influence the unusual repertoires of ribosome biogenesis factors.