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A human-specific mutation leads to the origin of a novel splice form of neuropsin (KLK8), a gene involved in learning and memory

Authors

  • Zhi-xiang Lu,

    1. Key Laboratory of Cellular and Molecular Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China
    2. Kunming Primate Research Center, Chinese Academy of Sciences, Kunming, China
    3. Graduate School, Chinese Academy of Sciences, Beijing, China
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  • Jia Peng,

    1. Key Laboratory of Cellular and Molecular Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China
    2. Kunming Primate Research Center, Chinese Academy of Sciences, Kunming, China
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  • Bing Su

    Corresponding author
    1. Key Laboratory of Cellular and Molecular Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, China
    2. Kunming Primate Research Center, Chinese Academy of Sciences, Kunming, China
    • Kunming Institute of Zoology, Chinese Academy of Sciences, 32 East Jiao-Chang Rd., Kunming 650223, Yunnan, China
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  • Communicated by David Cooper

Abstract

Neuropsin (kallikrein 8, KLK8) is a secreted-type serine protease preferentially expressed in the central nervous system and involved in learning and memory. Its splicing pattern is different in human and mouse, with the longer form (type II) only expressed in human. Sequence analysis suggested a recent origin of type II during primate evolution. Here we demonstrate that the type II form is absent in nonhuman primates, and is thus a human-specific splice form. With the use of an in vitro splicing assay, we show that a human-specific T to A mutation (c.71–127T>A) triggers the change of splicing pattern, leading to the origin of a novel splice form in the human brain. Using mutation assay, we prove that this mutation is not only necessary but also sufficient for type II expression. Our results demonstrate a molecular mechanism for the creation of novel proteins through alternative splicing in the central nervous system during human evolution. Hum Mutat 28(10), 978–984, 2007. © 2007 Wiley-Liss, Inc.

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