Molecular evolution of the neuropeptide Y receptor family : Insights from mammals and fish

Sammanfattning: Most genes in the genomes of vertebrates form families with multiple members that are more or less closely related. This thesis concerns investigations of the neuropeptide Y (NPY) family of peptides and the family of receptors to which these peptides bind, the NPY receptors. This ligand-receptor system relays signals through the cell membrane and is involved in the regulation of various responses including feeding, vasoconstriction, anxiolytic effects and gut activity.The vertebrate lineage diverged some 500 million years ago from the invertebrates, after which time two rounds of large-scale gene duplications are thought to have occurred. This played a major role in the generation of multigene families and facilitated evolution of the increased complexity of the vertebrates. To investigate the NPY receptor family, genes for different subtypes were isolated from mammals and bony fishes, primarily, pig and zebrafish. Analyses of DNA and protein sequences and genome location were used to deduce the evolution of these receptors. We propose that the three main receptor subtypes Y1, Y2, and Y5 arose through tandem duplications, as they are located in a cluster on the same chromosome. Their low sequence identities indicate that the duplications occurred prior to the radiation of the vertebrates. This cluster was subsequently duplicated through two large-scale duplications, generating the Y1-like genes Y4 and y6. Our results suggest that there are probably additional NPY receptor subtypes to be found in mammals as well as fishes. More detailed studies were carried out with regard to the evolution of the receptors in mammals through studies of the sister group to pigs, tayassuidae, represented by collared peccary. As well as studies of the functional properties of the fish NPY receptors and anatomical distribution of zebrafish NPY and PYY. Chromosomal mapping of thezebrafish genes encoding NPY and PYY to a region in conserved synteny with human strengthened the scheme previously proposed for the evolution of this peptide family.These studies provide evolutionary explanations for the complexity of the NPY-peptide and NPY-receptor families and will be helpful for future studies of this complicated receptor-ligand system.