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MIM.102980 18p11

Sunday 29 April 2007

Pituitary adenylate cyclase-activating polypeptide (PACAP) is a bioactive peptide that was originally isolated from ovine hypothalamus on the basis of its ability to stimulate adenylate cyclase in rat anterior pituitary cell cultures.

The N-terminal amino acid sequence of PACAP shares 68% identity with vasoactive intestinal peptide (VIP) (MIM.192320) and more limited similarity with growth hormone-releasing hormone (GHRH) (MIM.139190).

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.

Human evolution

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, it has been shown 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.

The PACAP precursor gene underwent adaptive changes during human origin and may have contributed to the formation of human cognition.


- Dorus, S.; Vallender, E. J.; Evans, P. D.; Anderson, J. R.; Gilbert, S. L.; Mahowald, M.; Wyckoff, G. J.; Malcom, C. M.; Lahn, B. T. : Accelerated evolution of nervous system genes in the origin of Homo sapiens. Cell 119: 1027-1040, 2004. PubMed ID : 15620360