title: Accelerated evolution of the pituitary adenylate cyclase-activating polypeptide precursor gene during human origin.
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.
authors.affiliation: Key Laboratory of Cellular and Molecular Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Yunnan.
authors.forename: Yin-Qiu
authors.initials: YQ
authors.lastname: Wang
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Qian
authors.forename: Su
authors.initials: S
authors.lastname: Yang
authors.forename: Hong
authors.initials: H
authors.lastname: Shi
authors.forename: Cheng-Hong
authors.initials: CH
authors.lastname: Liao
authors.forename: Hong-Kun
authors.initials: HK
authors.lastname: Zheng
authors.forename: Jun
authors.initials: J
authors.lastname: Wang
authors.forename: Alice A
authors.initials: AA
authors.lastname: Lin
authors.forename: L Luca
authors.initials: LL
authors.lastname: Cavalli-Sforza
authors.forename: Peter A
authors.initials: PA
authors.lastname: Underhill
authors.forename: Ranajit
authors.initials: R
authors.lastname: Chakraborty
authors.forename: Li
authors.initials: L
authors.lastname: Jin
authors.forename: Bing
authors.initials: B
authors.lastname: Su
mesh_terms: D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D005075:Biological Evolution; D001921:Brain / Q000378:metabolism; D003071:Cognition; D004247:DNA / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D019143:Evolution, Molecular; D005091:Exons; D006801:Humans; D051379:Mice; D008969:Molecular Sequence Data; D009474:Neurons / Q000378:metabolism; D002679:Pan troglodytes; D010802:Phylogeny; D016133:Polymerase Chain Reaction; D017434:Protein Structure, Tertiary; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
chemical_list: D017931:DNA Primers; D004247:DNA