Positive selection on schizophrenia-associated ST8SIA2 gene in post-glacial Asia

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  • 松井, 淳
    School of Advanced Sciences, SOKENDAI (The Graduate University for Advanced Studies), Hayama
  • Satta, Yoko
    School of Advanced Sciences, SOKENDAI (The Graduate University for Advanced Studies), Hayama
  • Hane, Masaya
    Bioscience and Biotechnology Center, Nagoya University
  • Matsui, Atsushi
    Primate Research Institute, Kyoto University
  • Yashima, Kenta
    School of Advanced Sciences, SOKENDAI (The Graduate University for Advanced Studies), Hayama
  • Kitajima, Ken
    Bioscience and Biotechnology Center, Nagoya University
  • Sato, Chihiro
    ioscience and Biotechnology Center, Nagoya University
  • Takahata, Naoyuki
    School of Advanced Sciences, SOKENDAI (The Graduate University for Advanced Studies), Hayama
  • Hayakawa, Toshiyuki
    Graduate School of Systems Life Sciences, Kyushu University･Faculty of Arts and Science, Kyushu University
  • Kazuya Iwamoto
    editor

説明

A number of loci are associated with highly heritable schizophrenia and the prevalence of this mental illness has had considerable negative fitness effects on human populations. Here we focused on one particular schizophrenia-associated gene that encodes a sialyltransferase (ST8SIA2) and is expressed preferentially in the brain with the level being largely determined by three SNPs in the promoter region. It is suggested that the expression level of the ST8SIA2 gene is a genetic determinant of schizophrenia risk, and we found that a geographically differentiated non-risk SNP type (CGC-type) has significantly reduced promoter activity. A newly developed method for detecting ongoing positive selection was applied to the ST8SIA2 genomic region with the identification of an unambiguous sweep signal in a rather restricted region of 18 kb length surrounding the promoter. We also found that while the CGC-type emerged in anatomically modern humans in Africa over 100 thousand years ago, it has increased its frequency in Asia only during the past 20–30 thousand years. These findings support that the positive selection is driven by psychosocial stress due to changing social environments since around the last glacial maximum, and raise a possibility that schizophrenia extensively emerged during the Upper Paleolithic and Neolithic era.

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  • PLOS ONE

    PLOS ONE 13 (7), e0200278-, 2018-07-25

    Public Library of Science (PLoS)

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