Neuropeptide families and their receptors: evolutionary perspectives.

Examination of families of neuropeptides and their receptors can provide information about phyletic relationships and evolutionary processes. Within an individual a given signal molecule may serve many diverse functions, mediated via subtypes of the receptor which may be coupled to their transduction mechanisms in different ways. The rate of evolution of a peptide may reflect or be reflected in the rate of evolution of its receptor. For example, in the neuropeptide Y (NPY) family, pancreatic polypeptide (PP) shows significant structural diversity, while NPY is highly conserved. Molecular forms of a given subtype of NPY receptor that is selectively activated by NPY (Y1 or Y2 or Y5) are also highly conserved, but the subtype that is primarily activated by PP (Y4), shows remarkable diversity. Also, between receptor subtypes there can be remarkable diversity. This is evident in several neuropeptide families, where a neuropeptide sequence is highly conserved across a wide range of species but where the receptor homology of subtypes with species tends to be much lower than homology between species. For example, human and rat vasopressin are identical, but the human V(1)- or V(2)-vasopressin receptors are approximately 80% homologous with rat V(1)- or V(2)-receptors, but within humans or rats the V(1)-receptor is less than 50% homologous with the V(2)-receptor. Furthermore, duplication of an ancestral gene is thought to have led to the co-presence in eutherian mammals of oxytocin and vasopressin, which have maintained a close structural similarity, yet in many species the oxytocin receptor is only 30 to 50% homologous with vasopressin receptors. Thus it appears that there has been greater evolutionary pressure to conserve the signal molecule, than to conserve the structure of the receptor. Evaluation of the evolution of neuropeptides and their receptors may be useful in determining phyletic relationships. Traditional classification places the guinea pig as a hystricomorph rodent within the same order (Rodentia) as the muriform or myomorph rat and mouse. However, molecular analyses of polypeptides have led to the suggestion that guinea pigs belong to a distinct order. Analysis of several neuropeptide sequences and the Y4 receptor supports this view. In general terms for both neuropeptides and receptors, sequence homology reflects phylogeny and taxonomy as based on morphological features. Within the oxytocin/vasopressin family in which peptides and receptors have been characterised in invertebrate representatives as well as fish and amphibia in addition to mammals, the molecular diversity correlates well with evolutionary diversity.