Peptide YY-2 (PYY2) and pancreatic polypeptide-2 (PPY2): species-specific evolution of novel members of the neuropeptide Y gene family.

Abstract Several gene duplication events have led to the creation of at least five distinct members of the neuropeptide Y gene family. We now reveal that the most recent of these events, involving the PYY–PPY gene cluster on chromosome 17q21.1, has led to the creation of novel PYY- and PP-like genes on chromosome 17q11 in the human genome. Sequence analysis of the novel human PYY2 and PPY2 genes shows an extensive homology to the peptide YY–pancreatic polypeptide genes, at the level of gene structure, nucleotide sequence, and primary amino acid sequence. The extremely high degree of homology between the PYY–PPY and the PYY2–PPY2 gene clusters, in both coding regions and especially noncoding regions, suggests that the PYY2 and PPY2 genes have arisen by a very recent gene duplication. Similar gene duplication events of the PYY–PPY gene cluster have also occurred in other species, including cow and baboon, but have not been confirmed in the rat and mouse genomes. Interestingly, despite the greater than 92% nucleotide sequence identity between these new genes, a few specific mutations have resulted in significantly altered peptide sequences. These altered sequences are accompanied by acquisition of new functions apparently unrelated to the neurotransmitter/endocrine role of PYY and PPY, as demonstrated by the major involvement of bovine PYY2, also known as seminalplasmin, in the fertilization process.