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

Several gene duplication events have led to the creation of at least five d istinct members of the neuropeptide Y gene family. We now reveal that the m ost recent of these events, involving the PYY-PPY gene cluster on chromosom e 17q21.1, has led to the creation of novel PYY- and PP-like genes on chrom osome 17q11 in the human genome. Sequence analysis of the novel human PYY2 and PPY2 genes shows an extensive homology to the peptide W-pancreatic poly peptide genes, at the level of gene structure, nucleotide sequence, and pri mary amino acid sequence. The extremely high degree of homology between the PYY-PPY and the PYY2-PPY2 gene clusters, in both coding regions and especi ally noncoding regions, suggests that the PYY2 and PPY2 genes have arisen b y a very recent gene duplication. Similar gene duplication events of the PY Y-PPY gene cluster have also occurred in other species, including cow and b aboon, but have not been confirmed in the rat and mouse genomes. Interestin gly, despite the greater than 92% nucleotide sequence identity between thes e new genes, a few specific mutations have resulted in significantly altere d peptide sequences. These altered sequences are accompanied by acquisition of new functions apparently unrelated to the neurotransmitter/ endocrine r ole of PYY and PPY, as demonstrated by the major involvement of bovine PYY2 , also known as seminalplasmin, in the fertilization process, (C) 2000 acad emic Press.