Molecular biology and evolution最新文献

Ornamental medaka strains derived from wild Japanese medaka (Oryzias latipes species complex) are bred worldwide. Over 200 years of selective breeding have produced over 700 strains with a wide variety of phenotypes, including diverse body coloration, scales, eyeball morphology, and fin and body shapes. In this study, we first identified and described 34 phenotypes in ornamental medaka strains. To understand the genomic basis of this phenotypic diversity and the domestication process, we performed whole genome sequencing on 181 individuals of 86 ornamental Japanese medaka strains. Population genomic analyses revealed that modern ornamental medaka strains are genetically closer to the wild Southern Japan population of the Kansai-Setouchi regions, suggesting the origin of ornamental strains. In addition, the gene loci poc1a, tyr, nme2a, and gabrr2b have undergone selection during domestication. We performed GWAS analysis for 29 phenotypes observed in ornamental medaka strains and identified strong candidate genes for some phenotypes, including kcnq5a for hirenaga and swallow, bmp5 for deme, adcy5 for orochi, and kitlga for aurora, respectively. We found that loss of exon 8 of adcy5 caused melanism, a dark body color phenotype, in medaka, providing a molecular insight on this phenomenon in vertebrates and human inherent dyskinesia. In addition, we uncovered the predominant candidate peaks of GWAS, including a total of 3,328 genes associated with 26 phenotypes. Our findings highlight the potential of population genomics to explore genotype-phenotype correlations and the genomic basis of body coloration and morphogenesis in medaka.

The genetics of complex traits has been fundamentally transformed by the dramatic reduction in short-read sequencing costs, leading to a dramatic reversal in the relative costs of genotyping versus phenotyping. We explore this new scientific landscape by examining key experimental strategies that leverage inexpensive sequencing, including low-coverage whole-genome sequencing with imputation (lcWGS+I) for genotyping large cohorts. Although somewhat limited in outbred populations, lcWGS+I can be extremely effective in multi-parent populations (MPPs) and in founder-unknown closed colonies, where imputation accuracy can exceed 98%. We further explore pooled-sequencing (Pool-seq) approaches for dissecting complex traits, such as Evolve and Resequence (E&R) for tracking adaptive changes in allele frequency over several generations, and Extreme QTL (X-QTL) mapping that identifies loci by contrasting pooled samples from phenotypic extremes. We show that X-QTL mapping in MPPs, by testing for shifts in founder haplotype frequencies across small genomic windows, can be extremely powerful and cost-effective. Finally, we discuss methods where sequencing reads serve as the phenotype itself. DNA barcoding enables massive-scale fitness assays, while the "*-seq" toolkit (e.g., RNA-seq, ATAC-seq) allows for mapping molecular QTLs, though this introduces a significant multiple testing burden. Systems leveraging certain breeding designs in concert with low cost sequencing can greatly accelerate progress towards a mechanistic understanding of the genotype-phenotype relationship.

Meiotic drivers are selfish genetic elements that gain transmission advantages by distorting equal, Mendelian segregation. For decades, biologists have considered meiotic drivers as interesting, albeit esoteric, case studies. It is now clear, however, that meiotic drive is more common and phylogenetically widespread than previously supposed. Indeed, intensive study of a few well-known cases has begun to reveal the evolutionary genomic consequences of meiotic drive. We argue here that many features of genome evolution, content, and organization that are seemingly inexplicable by organismal adaptation or nearly neutral processes are instead best accounted for by recurrent histories of meiotic drive. We review how meiotic drive can affect the evolution of sequences, gene copy numbers, genes with functions in meiosis and gametogenesis, signatures of "selection", chromosome rearrangements, and karyotype evolution. We also explore the interactions of meiotic drive elements with other classes of selfish genetic elements, including satellite DNAs, transposable elements, and with the endogenous host genes involved in drive suppression. Finally, we argue that some aspects of drive-mediated genome evolution are now sufficiently well established that we might reverse the direction of discovery- rather than ask how drive affects genome evolution, we can use genome data to discover new putative drive elements.

Adaptation to ant and/or termite consumption (myrmecophagy) in mammals constitutes a textbook example of convergent evolution, being independently derived in several mammalian lineages. Myrmecophagous species are characterized by striking convergent morphological adaptations such as skull elongation, enlargement of salivary glands, and long claws to dig into ant and termite nests. These evolutionary modifications also include anatomical regression, such as dental simplification or loss, reduction of masticatory muscles, and possessing a reduced set of taste buds. To gain insights into the molecular changes underlying the regression of these morpho-anatomical traits, we investigated the functionality of candidate genes related to dentition, gustation, and mastication in nine convergent myrmecophagous mammalian lineages. We examined these genes in a comparative phylogenetic context, paired with molecular evolutionary analyses, to estimate the relative timing of loss of gene function over the evolutionary history of each convergent lineage. We found that gustatory reduction and pseudogenization of masticatory myosin often were associated with the regression of dental genes. Evidence of pseudogenization events linked to oral anatomy dates to as early as the Cretaceous/Paleogene boundary, and is an ongoing process including examples of incipient gene inactivations. Whereas we found evidence for gene inactivations across all three functional categories occurring during distinct temporal intervals, there was variation in the sets of genes lost and the relative timing of inactivation events. The combined evidence suggests that the convergent evolution of myrmecophagy has occurred as a protracted process with distinct phases of anatomical evolution, over timescales as long as 60 Myr.

Ancient and modern genomic data provide insights into continuous human migrations and subsequent admixture and gene flow throughout human history. These demographic events and natural selection contribute to the genetic and phenotypic variation that gives the African population its unique characteristics. This genomic data have provided scientists with insights into complex migratory events, patterns of admixture and the spatial distribution of ancestral lineages. For example, the return migration from western Eurasia to Africa introduced pastoralism, and the remarkable expansion of Bantu-speaking groups brought agricultural practices to a wider area of eastern and southern Africa. In addition, the continent's vast and diverse environmental conditions as well as complex human history and higher-level genetic diversity contribute to varying degrees of susceptibility and resistance to complex diseases. With all these complex demographic histories of African populations and a multi-ethnic genomic diversity, it remains essential to deepen our understanding of the genetic basis of complex traits and diseases. This review provides an overview of insights into population admixture and complex disease states based on data from ancient and modern genomes. These include the major waves of population movement and patterns of admixture that influence the diverse, complex traits observed among populations within the African continent. Overall, this review will provide a deep insight into prehistoric demographic events and the genomic profiles of modern Africans and highlights the importance of integrated international cooperation to strengthen African genomics research.

Cancer as a selective force in human evolution remains largely unexplored in the field of cancer evolution and ecology. In this review, we examine one such proposal about the evolution of skin pigmentation in ancestral humans. The skin cancer hypothesis posits that deaths from sun-induced skin cancers in part favored the evolution of darker skin in early hominins as they dispersed into savanna mosaics. Evolutionary mismatch, where migrants and albinos with fair or extremely pale skin settle in high-UVR environments, has been used to support the hypothesis, but only the case involving albinos has been subject to examination and discussion. Using current data on skin cancer rates in Australians, we test the case of migration-related mismatch and find that, although skin cancers with metastatic potential are common, their typical onset occurs after reproductive age. This suggests that the protective effects of dark skin in ancestral humans were likely selected not for protection against skin cancers, but for mitigating other UV-related risks, e.g. maintaining thermoregulation and water barrier integrity. We then discuss several ad hoc explanations, and their criticisms, to preserve the skin cancer hypothesis, concerning melanoma as a selection pressure, life history traits of ancestral humans, and the grandmother effect. We conclude that lethal skin cancers may have shaped human evolution indirectly, insofar as post-reproductive elderly contributed to ancestral social structures by providing alloparental care to their kin.

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.