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doi:10.1534/genetics.105.040527
A more recent version of this article appeared on June 1, 2005.
REGULAR RESEARCH PAPERS |
Accelerated Evolution of the PACAP Precursor Gene During Human Origin
Yinqiu Wang 1, Yaping Qian 2, Su Yang 1, Hong Shi 1, Chenghong Liao 1, Hongkun Zheng 3, Jun Wang 3, Alice Lin 4, Luca Cavalli-Sforza 4, Peter Underhill 4, Ranajit Chakraborty 2, Li Jin 2 and Bing Su 5*
1 Kunming Institute of Zoology, Chinese Academy of Sciences
2 Center for Genome Information, University of Cincinnati
3 Beijing Genomics Institute, Chinese Academy of Sciences
4 Stanford University
5 Kunming Institute of Zoology, Chinese Academy of Science
* To whom correspondence should be addressed. E-mail: sub{at}mail.kiz.ac.cn.
Submitted on January 5, 2005
Revised on February 8, 2005
Accepted on 2 March 2005
Pituitary adenylate cyclase-activating polypeptide (PACAP) is a neuropeptide abundantly expressed in the central nervous system, and involved in regulating neurogenesis and neuronal signal transduction. The amino acid sequence of PACAP is extremely conserved across vertebrate species, indicating a strong functional constraint during the course of evolution. However, through comparative sequence analysis, we demonstrated that the PACAP precursor gene underwent an accelerated evolution in the human lineage since the divergence from chimpanzees, and the amino acid substitution rate in humans is at least seven times faster than in other mammal species resulting from strong Darwinian positive selection. Eleven human-specific amino acid changes were identified in the PACAP precursors which are conserved from murine to African apes. Protein structural analysis suggested that a putative novel neuropeptide might have originated during human evolution and functioned in the human brain. Our data suggested that the PACAP precursor gene underwent adaptive changes during human origin and may contribute to the formation of human cognition.
Key Words: Darwinian positive selection, PACAP, brain evolujtion, human origin
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