Molecular biology and evolution最新文献

Sex chromosomes are widespread in species with separate sexes. They have evolved many times independently and display a truly remarkable diversity. New sequencing technologies and methodological developments have allowed the field of molecular evolution to explore this diversity in a large number of model and nonmodel organisms, broadening our vision on the mechanisms involved in their evolution. Diverse studies have allowed us to better capture the common evolutionary routes that shape sex chromosomes; however, we still mostly fail to explain why sex chromosomes are so diverse. We review over half a century of theoretical and empirical work on sex chromosome evolution and highlight pending questions on their origins, turnovers, rearrangements, degeneration, dosage compensation, gene content, and rates of evolution. We also report recent theoretical progress on our understanding of the ultimate reasons for sex chromosomes' existence.

Caspase-1 and related proteases are key players in inflammation and innate immunity. Here, we characterize the evolutionary history of caspase-1 and its close relatives across 19 primates and 21 rodents, focusing on differences that may cause discrepancies between humans and animal studies. While caspase-1 has been retained in all these taxa, other members of the caspase-1 subfamily (caspase-4, -5, -11, -12, and CARD16, 17, and 18) each have unique evolutionary trajectories. Caspase-4 is found across simian primates, whereas we identified multiple pseudogenization and gene loss events in caspase-5, caspase-11, and the CARDs. Because caspases-4 and -11 are both key players in the non-canonical inflammasome pathway, we expected that these proteins would be likely to evolve rapidly. Instead, we found that these two proteins are largely conserved, whereas caspase-4's close paralog, caspase-5, showed significant indications of positive selection, as did primate caspase-1. Caspase-12 is a non-functional pseudogene in humans. We find this extends across most primates, although many rodents and some primates retain an intact, and likely functional, caspase-12. In mouse laboratory lines, we found that 50% of common strains carry non-synonymous variants that may impact the functions of caspase-11 and -12, and therefore recommend specific strains to be used (and avoided). Finally, unlike rodents, primate caspases have undergone repeated rounds of gene conversion, duplication, and loss leading to a highly dynamic pro-inflammatory caspase repertoire. Thus we uncovered many differences in the evolution of primate and rodent pro-inflammatory caspases, and discuss the potential implications of this history for caspase gene functions.

Hybrid sterility is a reproductive isolation barrier between diverging taxa securing the early steps of speciation. Hybrid sterility is ubiquitous in the animal and plant kingdoms, but its genetic control is poorly understood. In our previous studies, we have uncovered the sterility of hybrids between musculus and domesticus subspecies of the house mouse, which is controlled by the Prdm9 gene, the X-linked Hstx2 locus, and subspecific heterozygosity for genetic background. To further investigate this form of genic-driven chromosomal sterility, we constructed a simplified hybrid sterility model within the genome of the domesticus subspecies by swapping domesticus autosomes with their homologous partners from the musculus subspecies. We show that the "sterility" allelic combination of Prdm9 and Hstx2 can be activated by a musculus/domesticus heterozygosity of as few as two autosomes, Chromosome 17 (Chr 17) and Chr 18 and is further enhanced when another heterosubspecific autosomal pair is present, whereas it has no effect on meiotic progression in the pure domesticus genome. In addition, we identify a new X-linked hybrid sterility locus, Hstx3, at the centromeric end of Chr X, which modulates the incompatibility between Prdm9 and Hstx2. These results further support our concept of chromosomal hybrid sterility based on evolutionarily accumulated divergence between homologous sequences. Based on these and previous results, we believe that future studies should include more information on the mutual recognition of homologous chromosomes at or before the first meiotic prophase in interspecific hybrids, as this may serve as a general reproductive isolation checkpoint in mice and other species.

Ancient environmental DNA (aeDNA) is becoming a powerful tool to gain insights about past ecosystems, overcoming the limitations of conventional fossil records. However, several methodological challenges remain, particularly for classifying the DNA to species level and conducting phylogenetic analysis. Current methods, primarily tailored for modern datasets, fail to capture several idiosyncrasies of aeDNA, including species mixtures from closely related species and ancestral divergence. We introduce soibean, a novel tool that utilizes mitochondrial pangenomic graphs for identifying species from aeDNA reads. It outperforms existing methods in accurately identifying species from multiple closely related sources within a sample, enhancing phylogenetic analysis for aeDNA. soibean employs a damage-aware likelihood model for precise identification at low coverage with a high damage rate. Additionally, we reconstructed ancestral sequences for soibean's database to handle aeDNA that is highly diverged from modern references. soibean demonstrates effectiveness through simulated data tests and empirical validation. Notably, our method uncovered new empirical results in published datasets, including using porpoise whales as food in a Mesolithic community in Sweden, demonstrating its potential to reveal previously unrecognized findings in aeDNA studies.

Understanding variation in chromatin contact patterns across diverse humans is critical for interpreting noncoding variants and their effects on gene expression and phenotypes. However, experimental determination of chromatin contact patterns across large samples is prohibitively expensive. To overcome this challenge, we develop and validate a machine learning method to quantify the variation in 3D chromatin contacts at 2 kilobase resolution from genome sequence alone. We apply this approach to thousands of human genomes from the 1000 Genomes Project and the inferred hominin ancestral genome. While patterns of 3D contact divergence genome wide are qualitatively similar to patterns of sequence divergence, we find substantial differences in 3D divergence and sequence divergence in local 1 megabase genomic windows. In particular, we identify 392 windows with significantly greater 3D divergence than expected from sequence. Moreover, for 31% of genomic windows, a single individual has a rare divergent 3D contact map pattern. Using in silico mutagenesis, we find that most single nucleotide sequence changes do not result in changes to 3D chromatin contacts. However, in windows with substantial 3D divergence just one or a few variants can lead to divergent 3D chromatin contacts without the individuals carrying those variants having high sequence divergence. In summary, inferring 3D chromatin contact maps across human populations reveals variable contact patterns. We anticipate that these genetically diverse maps of 3D chromatin contact will provide a reference for future work on the function and evolution of 3D chromatin contact variation across human populations.

Sheep was one of the first domesticated animals in Neolithic West Eurasia. The zooarchaeological record suggests that domestication first took place in Southwest Asia, although much remains unresolved about the precise location(s) and timing(s) of earliest domestication, or the post-domestication history of sheep. Here, we present 24 new partial sheep paleogenomes, including a 13,000-year-old Epipaleolithic Central Anatolian wild sheep, as well as 14 domestic sheep from Neolithic Anatolia, two from Neolithic Iran, two from Neolithic Iberia, three from Neolithic France, and one each from Late Neolithic/Bronze Age Baltic and South Russia, in addition to five present-day Central Anatolian Mouflons and two present-day Cyprian Mouflons. We find that Neolithic European, as well as domestic sheep breeds, are genetically closer to the Anatolian Epipaleolithic sheep and the present-day Anatolian and Cyprian Mouflon than to the Iranian Mouflon. This supports a Central Anatolian source for domestication, presenting strong evidence for a domestication event in SW Asia outside the Fertile Crescent, although we cannot rule out multiple domestication events also within the Neolithic Fertile Crescent. We further find evidence for multiple admixture and replacement events, including one that parallels the Pontic Steppe-related ancestry expansion in Europe, as well as a post-Bronze Age event that appears to have further spread Asia-related alleles across global sheep breeds. Our findings mark the dynamism of past domestic sheep populations in their potential for dispersal and admixture, sometimes being paralleled by their shepherds and in other cases not.

Transcriptional enhancers orchestrate cell type- and time point-specific gene expression programs. Genetic variation within enhancer sequences is an important contributor to phenotypic variation including evolutionary adaptations and human disease. Certain genes and pathways may be more prone to regulatory evolution than others, with different patterns across diverse organisms, but whether such patterns exist has not been investigated at a sufficient scale. To address this question, we identified signatures of accelerated sequence evolution in conserved enhancer elements throughout the mammalian phylogeny at an unprecedented scale. While different genes and pathways were enriched for regulatory evolution in different parts of the tree, we found a striking overall pattern of pleiotropic genes involved in gene regulatory and developmental processes being enriched for accelerated enhancer evolution. These genes were connected to more enhancers than other genes, which was the basis for having an increased amount of sequence acceleration over all their enhancers combined. We provide evidence that sequence acceleration is associated with turnover of regulatory function. Detailed study of one acceleration event in an enhancer of HES1 revealed that sequence evolution led to a new activity domain in the developing limb that emerged concurrently with the evolution of digit reduction in hoofed mammals. Our results provide evidence that enhancer evolution has been a frequent contributor to regulatory innovation at conserved developmental signaling genes in mammals.

Interspecific introgression is a potentially important source of novel variation of adaptive significance. Although multiple cases of adaptive introgression are well documented, broader generalizations about its targets and mechanisms are lacking. Multiallelic balancing selection, particularly when acting through rare allele advantage, is an evolutionary mechanism expected to favor adaptive introgression. This is because introgressed alleles are likely to confer an immediate selective advantage, facilitating their establishment in the recipient species even in the face of strong genomic barriers to introgression. Vertebrate major histocompatibility complex genes are well-established targets of long-term multiallelic balancing selection, so widespread adaptive major histocompatibility complex introgression is expected. Here, we evaluate this hypothesis using data from 29 hybrid zones formed by fish, amphibians, squamates, turtles, birds, and mammals at advanced stages of speciation. The key prediction of more extensive major histocompatibility complex introgression compared to genome-wide introgression was tested with three complementary statistical approaches. We found evidence for widespread adaptive introgression of major histocompatibility complex genes, providing a link between the process of adaptive introgression and an underlying mechanism. Our work identifies major histocompatibility complex introgression as a general mechanism by which species can acquire novel, and possibly regain previously lost, variation that may enhance defense against pathogens and increase adaptive potential.

It has been proposed that the phenotypic differences in cognitive abilities between humans and our closest living relatives, chimpanzees, are largely due to changes in the regulation of neurodevelopmental genes. We have previously found that the neurodevelopmental transcription factor gene NPAS3 accumulates the largest number of human accelerated regions (HARs), suggesting it may play some role in the phenotypic evolution of the human nervous system. In this work, we performed a comparative functional analysis of NPAS3-HAR202 using enhancer reporter assays in transgenic zebrafish and mice. We found that the Homo sapiens HAR202 ortholog failed to drive reporter expression to the zebrafish nervous system, in high contrast to the strong expression displayed by the rest of the vertebrate ortholog sequences tested. Remarkably, the HAR202 ortholog from archaic humans (Neanderthals/Denisovans) also displayed a pan-vertebrate expression pattern, despite the fact that archaic and modern humans have only one nucleotide substitution. Moreover, similar results were found when comparing enhancer activity in transgenic mice, where we observed a loss of activity of the modern human version in the mouse developing brain. To investigate the functional importance of HAR202, we generated mice lacking HAR202 and found a remarkable decrease of Npas3 expression in the forebrain during development. Our results place HAR202 as one of the very few examples of a neurodevelopmental transcriptional enhancer displaying functional evolution in the brain as a result of a fast molecular evolutionary process that specifically occurred in the human lineage.

Plasmids are ubiquitous mobile genetic elements, that can be either costly or beneficial for their bacterial host. In response to constant viral threat, bacteria have evolved various immune systems, such as the prevalent restriction modification (innate immunity) and CRISPR-Cas systems (adaptive immunity). At the molecular level, both systems also target plasmids, but the consequences of these interactions for plasmid spread are unclear. Using a modeling approach, we show that restriction modification and CRISPR-Cas are effective as barriers against the spread of costly plasmids, but not against beneficial ones. Consequently, bacteria can profit from the selective advantages that beneficial plasmids confer even in the presence of bacterial immunity. While plasmids that are costly for bacteria may persist in the bacterial population for a certain period, restriction modification and CRISPR-Cas can eventually drive them to extinction. Finally, we demonstrate that the selection pressure imposed by bacterial immunity on costly plasmids can be circumvented through a diversity of escape mechanisms and highlight how plasmid carriage might be common despite bacterial immunity. In summary, the population-level outcome of interactions between plasmids and defense systems in a bacterial population is closely tied to plasmid cost: Beneficial plasmids can persist at high prevalence in bacterial populations despite defense systems, while costly plasmids may face extinction.