Neuropeptide families: evolutionary perspectives.

Examination of neuropeptide families can provide information about phyletic relationships and evolutionary processes. In this article the oxytocin/vasopressin family, growth hormone releasing factor (GRF) superfamily and the substance P/tachykinin family have been considered in detail because they have been isolated from an extraordinarily diverse array of species from several vertebrate classes and invertebrate phyla. More important is that the nucleotide sequence of mRNA or cDNA encoding many of these peptides has been determined, which has allowed evolutionary distances to be estimated based on the DNA mutation rate. The origin of a given family lies in a primordial gene that arose many millions of years ago, and through time, exon duplication and insertion, gene duplication, point mutation and exon loss, the family developed into the forms that are now recognised. For example, in birds, GRF and pituitary adenylate cyclase activating peptide (PACAP) are encoded by the same gene, which probably arose as a result of exon duplication and tandem insertion of the ancestral GRF gene. In mammals GRF is the sole product on one gene, and PACAP is the product of a gene that also produces PACAP-related peptide (PRP), which is homologous to GRF. Thus it appears that between birds and mammals the GRF/PACAP gene duplicated: exon loss gave rise to the mammalian GRF gene, while mutation led to the formation of the mammalian PRP/PACAP gene. The neuropeptide Y superfamily is considered briefly, as is cionin, which is an invertebrate peptide that is closely related to the mammalian gastrin/cholecystokinin family.