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Originally published as Genetics Published Articles Ahead of Print on April 16, 2005.

Genetics, Vol. 170, 801-806, June 2005, Copyright © 2005
doi:10.1534/genetics.105.040527

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Accelerated Evolution of the Pituitary Adenylate Cyclase-Activating Polypeptide Precursor Gene During Human Origin

Yin-qiu Wang*,{dagger}, Ya-ping Qian{ddagger}, Su Yang*,{dagger}, Hong Shi*,{dagger}, Cheng-hong Liao*,{dagger}, Hong-Kun Zheng§, Jun Wang§, Alice A. Lin**, L. Luca Cavalli-Sforza**, Peter A. Underhill**, Ranajit Chakraborty{ddagger}, Li Jin{ddagger},{dagger}{dagger} and Bing Su*,{ddagger},1

* Key Laboratory of Cellular and Molecular Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650223, China
{ddagger} Center for Genome Information, Department of Environmental Health, University of Cincinnati, Cincinnati, Ohio 45267
§ Beijing Genomics Institute, Chinese Academy of Sciences, Beijing 101300, China
** Department of Genetics, Stanford University, Stanford, California 94305
{dagger}{dagger} State Key Laboratory of Genetics Engineering and Center for Anthropological Studies, School of Life Sciences, Fudan University, Shanghai 200433, China
{dagger} Graduate School of the Chinese Academy of Sciences, Beijing 100049, China

1 Corresponding author: Key Laboratory of Cellular and Molecular Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, 32 Jiao-Chang-Dong-Lu, Kunming, Yunan 650223, China.
E-mail: sub{at}mail.kiz.ac.cn

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 that 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 have contributed to the formation of human cognition.




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