Cloning of a neuropeptide Y/peptide YY receptor from the Atlantic cod: the Yb receptor

Neuropeptide Y (NPY) belongs to a family of structurally related neuroendocrine peptides that bind to G protein-coupled receptors. Five different receptor subtypes have recently been cloned in mammals and we have found another three receptor genes in the zebrafish, called zYa, zYb, and zYc, that appear to be distinct subtypes as deduced from their widely different sequences. To elucidate the evolutionary relationships between the mammalian and zebrafish receptors, we have used the zebrafish probes to isolate genomic clones from another teleost fish, the Atlantic cod, Gadus morhua. We present here the sequence of the cod Yb gene, whose deduced protein sequence is equally identical to the zebrafish Yb (69%) and Yc proteins (66%). The two zebrafish receptors are 76% identical to each other, suggesting that they arose by gene duplication in the zebrafish lineage after divergence from the cod lineage. The five cloned mammalian NPY-family receptors and the three cloned zebrafish NPY receptors indicate that this is the largest receptor family among all peptide receptors that belong to the superfamily of G protein-coupled receptors.