Proposed evolutionary history of GnIH and NPFF genes.

<p>GnIH and NPFF genes, originating from a common ancestral PQRFa gene, may have evolved through the whole-genome duplication. The amphioxus PQRFa peptides possess inhibitory action, suggesting that the common ancestor of GnIH and NPFF group peptides was an inhibitory peptide. After the 2 rounds of whole-genome duplications and subsequent loss of paralogous genes, the ancestral gene may have diverged into GnIH gene and NPFF gene. In the present vertebrates, GnIH group peptides inhibit GTH and GnRH in mammals, birds and fish, whereas they stimulate GTH in some fish and agnathans. NPFF group peptides modulate pain transmission in mammals and stimulate GTH in agnathans. It is possible that NPFF group peptides stimulate GTH in mammals and modulate pain transmission in agnathans.