Molecular evolution of NPY receptor subtypes

• Published in: Neuropeptides Vol. 38; no. 4; pp. 141 - 151
• Main Authors: Larhammar, D., Salaneck, E.
• Format: Book Review Journal Article
• Language: English
• Published: Netherlands Elsevier Ltd 01.08.2004
• Subjects: Amphibia; Animals; Appetite; Chromosomes, Human; Danio rerio; Evolution, Molecular; G-protein-coupled receptor; Gene Duplication; Humans; Lamprey; Neuropeptide Y - metabolism; Paralogon; Phylogeny; Protein Isoforms - genetics; Protein Isoforms - metabolism; Pseudogene; Receptors, Neuropeptide Y - classification; Receptors, Neuropeptide Y - genetics; Receptors, Neuropeptide Y - metabolism; Shark; Teleost fish; Tetraploidization; Tetrapod; Appetite; Pseudogene; Tetraploidization; Paralogon; Teleost fish; G-protein-coupled receptor; Shark; Gene duplication; Lamprey; Tetrapod
• ISSN: 0143-4179; 1532-2785
• DOI: 10.1016/j.npep.2004.06.002

The neuropeptide Y (NPY) system consists in mammals of three peptides and 4–5 G-protein-coupled receptors called Y receptors that are involved in a variety of physiological functions such as appetite regulation, circadian rhythm and anxiety. Both the receptor family and the peptide family display unexpected evolutionary complexity and flexibility as shown by information from different classes of vertebrates. The vertebrate ancestor most likely had a single peptide gene and three Y receptor genes, the progenitors of the Y 1, Y 2 and Y 5 subfamilies. The receptor genes were probably located in the same chromosomal segment. Additional gene copies arose through the chromosome quadruplication that took place before the emergence of jawed vertebrates (gnathostomes) whereupon differential losses of the gene copies ensued. The inferred ancestral gnathostome gene repertoire most likely consisted of two peptide genes, NPY and PYY, and no less than seven Y receptor genes: four Y 1-like (Y 1, Y 4/a, Y 6, and Y b), two Y 2-like (Y 2 and Y 7), and a single Y 5 gene. Whereas additional peptide genes have arisen in various lineages, the most common trend among the Y receptor genes has been further losses. Mammals have lost Y b and Y 7 (the latter still exists in frogs) and Y 6 is a pseudogene in several mammalian species but appears to be still functional in some. One challenge is to find out if mammals have been deprived of any functions through these gene losses. Teleost fishes like zebrafish and pufferfish, on the other hand, have lost the two major appetite-stimulating receptors Y 1 and Y 5. Nevertheless, teleost fishes seem to respond to NPY with increased feeding why some other subtype probably mediates this effect. Another challenge is to deduce how Y 2 and Y 4 came to evolve an inhibitory effect on appetite. Changes in anatomical distribution of receptor expression may have played an important part in such functional switching along with changes in receptor structures and ligand preferences.