Zebrafish Genes for Neuropeptide Y and Peptide YY Reveal Origin by Chromosome Duplication from an Ancestral Gene Linked to the Homeobox Cluster

Abstract

Neuropeptide Y (NPY) and peptide YY (PYY) are related 36-amino acid peptides. NPY is widely distributed in the nervous system and has several physiological roles. PYY serves as an intestinal hormone as well as a neuropeptide. We report here cloning of the npy and pyy genes in zebrafish (Danio rerio). NPY differs at only one to four amino acid positions from NPY in other jawed vertebrates. Zebrafish PYY differs at three positions from PYY from other fishes and at 10 positions from mammals. In situ hybridization showed that neurons containing NPY mRNA have a widespread distribution in the brain, particularly in the telencephalon, optic tectum, and rhombencephalon. PYY mRNA was found mainly in brainstem neurons, as reported previously for vertebrates as divergent as the rat and the lamprey, suggesting an essential role for PYY in these neurons. PYY mRNA was observed also in the telencephalon. These results were confirmed by immunocytochemistry. As in the human, the npy gene is located adjacent to homeobox (hox) gene cluster A (copy a in zebrafish), whereas the pyy gene is located close to hoxBa. This suggests that npy and pyy arose from a common ancestral gene in a chromosomal duplication event that also involved the hox gene clusters. As zebrafish has seven hox clusters, it is possible that additional NPY family genes exist or have existed. Also, the NPY receptor system seems to be more complex in zebrafish than in mammals, with at least two receptor genes without known mammalian orthologues.

Identification, tissue distribution and evaluation of brain neuropeptide Y gene expression in the Brazilian flounder Paralichthys orbignyanus

“…Rats submitted to chronic food restriction had differentially affected NPY gene expression in the hypothalamus and liver, suggesting that NPY expression may also be differentially regulated in other tissues (Sucajtys-Szulc et al 2008), while in fi sh it has not yet been demonstrated. Therefore, it may be risky to draw functional conclusions from anatomical studies in a single species (Soderberg et al 2000).…”

Birth and death of neuropeptide Y receptor genes in relation to the teleost fish tetraploidization

“…All tetrapods have three related peptides, namely NPY, peptide YY (PYY) and pancreatic polypeptide (PP) (Cerdá-Reverter and Larhammar, 2000). The NPY and PYY genes are located adjacent to Hox clusters and presumably arose as a result of a chromosome duplication prior to the origin of gnathostomes (Soderberg et al, 2000;. PP is a duplicate of PYY in tetrapods (Larhammar et al, 1998).…”

Chicken neuropeptide Y-family receptor Y4: a receptor with equal affinity for pancreatic polypeptide, neuropeptide Y and peptide YY

“…It is likely that pancreatic polypeptide and PYY stimulate Y4 receptor function in peripheral organs and that central functions are signalled by NPY. However, it will be interesting to see if PYY and pancreatic polypeptide are present in the chicken CNS, as PYY is more abundant in the CNS in fishes (Cerda-Reverter & Larhammar 2000, Söderberg et al 2000 and lamprey (Söderberg et al 1994) than in mammals.…”

“…NPY is extremely well conserved and has only one amino acid replacement between human and chicken, and four replacements between human and zebrafish (Blomqvist et al 1992, Larhammar 1996, CerdaReverter & Larhammar 2000, Söderberg et al 2000. PYY is more divergent, and pancreatic polypeptide differs greatly between species, with only 16 of 36 positions identical between human and chicken (Kimmel et al 1975, Larhammar 1996, Cerda-Reverter & Larhammar 2000.…”