Evolution of the Neuropeptide Y System in Vertebrates with Focus on Fishes

Sammanfattning: Gene families in vertebrates often contain more dulicates (paralogs) than in invertebrates. This has been attributed to genome duplications, i.e., tetraploidizations. Two of the gene families that have expanded in vertebrate evolution are the neuropeptide Y (NPY) family of peptides and the neuropeptide Y receptors (NPYR) that are involved in many brain functions including appetite regulation.Two NPYR genes, Y2 and Y7, were cloned in the rainbow trout. Although they arose from a common ancestral gene in early vertebrate evolution, their ligand-binding properties are very similar. Two NPYR genes were cloned in the coelacanth Latimeria chalumnae and found to be orthologs of Y5 and Y6 discovered in mammals.Analyses of gene families close to the NPYR genes in the pufferfishes T. nigroviridis and T. rubripes showed that at least 25 additional gene families had an evolutionary history similar to the NPYR family, thereby providing evidence for fish specific-duplications of these chromosomes. Cloning and phylogenetic analysis of 22 NPYR gene fragments from several ray-finned fishes showed that basal species seem to have the same repertoire as tetrapods. Despite the tetraploidization in the teleost fish lineage, many teleosts seem to have fever genes than the gnathostome ancestor due to gene loss. Only one duplicate seems to have survived.The NPY peptide family was found to have expanded in the teleost tetraploidization with duplicates of both NPY and PYY (peptide YY) in some teleosts. Fourteen neighboring gene families were found to have evolved in a similar manner as the NPY-family genes. Positional information fascilitated orthology assignment of peptide genes in teleost fishes and allowed correction of previously misidentified genes.In summary, the evolutionary history of the NPY and NPYR gene families involve large-scale duplication events coinciding with the proposed tetraploidizations. The appearance of new genes in early vertebrates and in teleost fishes probably had important implications for the evolution of new functions in this system.