Deep whole-genome sequencing reveals recent selection signatures linked to evolution and disease risk of Japanese

Yukinori Okada; Yukihide Momozawa; Saori Sakaue; Masahiro Kanai; Kazuyoshi Ishigaki; Masato Akiyama; Toshihiro Kishikawa; Yasumichi Arai; Takashi Sasaki; Kenjiro Kosaki; Makoto Suematsu; Koichi Matsuda; Kazuhiko Yamamoto; Michiaki Kubo; Nobuyoshi Hirose; Yoichiro Kamatani

doi:10.1038/s41467-018-03274-0

Deep whole-genome sequencing reveals recent selection signatures linked to evolution and disease risk of Japanese

Nat Commun. 2018 Apr 24;9(1):1631. doi: 10.1038/s41467-018-03274-0.

Authors

Yukinori Okada^{1

2

3}, Yukihide Momozawa⁴, Saori Sakaue^{5

6

7}, Masahiro Kanai^{5

6

8}, Kazuyoshi Ishigaki⁶, Masato Akiyama⁶, Toshihiro Kishikawa^{5

9}, Yasumichi Arai¹⁰, Takashi Sasaki¹⁰, Kenjiro Kosaki¹¹, Makoto Suematsu¹², Koichi Matsuda¹³, Kazuhiko Yamamoto¹⁴, Michiaki Kubo¹⁵, Nobuyoshi Hirose¹⁰, Yoichiro Kamatani^{6

16}

Affiliations

¹ Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan. [email protected].
² Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan. [email protected].
³ Laboratory of Statistical Immunology, Immunology Frontier Research Center (WPI-IFReC), Osaka University, Suita, 565-0871, Japan. [email protected].
⁴ Laboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
⁵ Department of Statistical Genetics, Osaka University Graduate School of Medicine, Suita, 565-0871, Japan.
⁶ Laboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
⁷ Department of Allergy and Rheumatology, Graduate School of Medicine, the University of Tokyo, Tokyo, 113-8655, Japan.
⁸ Department of Biomedical Informatics, Harvard Medical School, Boston, MA, 02115, USA.
⁹ Department of Otorhinolaryngology-Head and Neck Surgery, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan.
¹⁰ Center for Supercentenarian Medical Research, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo, 160-8582, Japan.
¹¹ Center for Medical Genetics, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo, 160-8582, Japan.
¹² Department of Biochemistry, Keio University School of Medicine, Shinanomachi 35, Shinjuku-ku, Tokyo, 160-8582, Japan.
¹³ Department of Computational Biology and Medical Sciences, Graduate school of Frontier Sciences, The University of Tokyo, Tokyo, 108-8639, Japan.
¹⁴ Laboratory for Autoimmune Diseases, RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
¹⁵ RIKEN Center for Integrative Medical Sciences, Yokohama, 230-0045, Japan.
¹⁶ Center for Genomic Medicine, Kyoto University Graduate School of Medicine, Sakyo-ku, Kyoto, 606-8507, Japan.

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.

Publication types

Meta-Analysis
Research Support, Non-U.S. Gov't

MeSH terms

Aldehyde Dehydrogenase, Mitochondrial / genetics
Animals
Asian People / genetics*
Disease / genetics*
Evolution, Molecular*
Gene Frequency
Genome, Human*
Genome-Wide Association Study
Hominidae / genetics
Humans
Japan
Polymorphism, Single Nucleotide
Quantitative Trait Loci
Selection, Genetic
Whole Genome Sequencing

Substances

ALDH2 protein, human
Aldehyde Dehydrogenase, Mitochondrial