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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
Author(s) -
Lu Zhixiang,
Peng Jia,
Su Bing
Publication year - 2007
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.20547
Subject(s) - biology , rna splicing , alternative splicing , mutation , splice , genetics , splice site mutation , gene , microbiology and biotechnology , exon , rna
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.