Abstract
Understanding natural selection is crucial to unveiling evolution of modern humans. Here, we report natural selection signatures in the Japanese population using 2234 high-depth whole-genome sequence (WGS) data (25.9×). Using rare singletons, we identify signals of very recent selection for the past 2000–3000 years in multiple loci (ADH cluster, MHC region, BRAP-ALDH2, SERHL2). In large-scale genome-wide association study (GWAS) dataset (n = 171,176), variants with selection signatures show enrichment in heterogeneity of derived allele frequency spectra among the geographic regions of Japan, highlighted by two major regional clusters (Hondo and Ryukyu). While the selection signatures do not show enrichment in archaic hominin-derived genome sequences, they overlap with the SNPs associated with the modern human traits. The strongest overlaps are observed for the alcohol or nutrition metabolism-related traits. Our study illustrates the value of high-depth WGS to understand evolution and their relationship with disease risk.
Highlights
Understanding natural selection is crucial to unveiling evolution of modern humans
Given dense mapping of the variants obtained through highthroughput single-nucleotide polymorphism (SNP) array and whole-genome sequencing (WGS), a variety of analytical methods, such as F-statistics (FST)[2], integrated haplotype score[3], cross-population extended haplotype homozygosity (XP-EHH)[4], and composite of multiple signals (CMS)[5], have been developed to fine-map natural selection signatures embedded in the human genome sequences
We assessed site frequency spectrum (SFS) of the wholegenome sequence (WGS) datasets, as well as those in worldwide populations obtained from the Genome Aggregation Database[17] and the UK10K project[13] (Fig. 1a and Supplementary Fig. 2)
Summary
Understanding natural selection is crucial to unveiling evolution of modern humans. Here, we report natural selection signatures in the Japanese population using 2234 high-depth wholegenome sequence (WGS) data (25.9×). Given dense mapping of the variants obtained through highthroughput single-nucleotide polymorphism (SNP) array and whole-genome sequencing (WGS), a variety of analytical methods, such as F-statistics (FST)[2], integrated haplotype score (iHS)[3], cross-population extended haplotype homozygosity (XP-EHH)[4], and composite of multiple signals (CMS)[5], have been developed to fine-map natural selection signatures embedded in the human genome sequences These methods have successfully detected genetic loci under extensive natural selection, which highlighted relationship between human evolution and both monogenic traits (e.g., lactose tolerance at LCT in Europeans[6], high-altitude adaptations at EPAS1 in Tibetans[7], and malaria resistance at HBB in Africans8) and polygenic traits (e.g., anthropometric traits[9,10,11]). We examine selection signature profiles on human genome sequences derived from archaic hominins, as well as risk variants on a range of modern human complex traits, to assess underlying impacts of adaptive evolution in Japanese
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