Accelerated evolution of the pituitary adenylate cyclase-activating polypeptide precursor gene during human origin

Yin Qiu Wang, Ya Ping Qian, Su Yang, Hong Shi, Cheng Hong Liao, Hong Kun Zheng, Jun Wang, Alice A. Lin, L. Luca Cavalli-Sforza, Peter A. Underhill, Ranajit Chakraborty, Li Jin, Bing Su

Research output: Contribution to journalArticlepeer-review

25 Scopus citations

Abstract

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.

Original languageEnglish
Pages (from-to)801-806
Number of pages6
JournalGenetics
Volume170
Issue number2
DOIs
StatePublished - Jun 2005

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