1098-1004/asset/cover.gif?v=1&s=b02ab57a64d28403f477b09d50f72a4d63f4c8eb "Human Mutation")
Communicated by David Cooper
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Research Article
A human-specific mutation leads to the origin of a novel splice form of neuropsin (KLK8), a gene involved in learning and memory†
Article first published online: 8 MAY 2007
DOI: 10.1002/humu.20547
© 2007 Wiley-Liss, Inc.
Additional Information
How to Cite
Lu, Z.-x., Peng, J. and Su, B. (2007), A human-specific mutation leads to the origin of a novel splice form of neuropsin (KLK8), a gene involved in learning and memory. Hum. Mutat., 28: 978–984. doi: 10.1002/humu.20547
- †
Publication History
- Issue published online: 6 SEP 2007
- Article first published online: 8 MAY 2007
- Manuscript Accepted: 26 MAR 2007
- Manuscript Received: 10 FEB 2007
Funded by
- Natural Science Foundation of Yunnan Province of China
- Chinese Academy of Sciences. Grant Number: KSCX1-YW-R-34
- National Natural Science Foundation of China. Grant Numbers: 30370755, 30525028, 30630013
- National 973 Project of China. Grant Number: 2006CB701506
Keywords:
- neuropsin;
- kallikrein 8;
- KLK8;
- alternative splicing;
- cognition;
- human evolution
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.