A neuropeptide Y receptor Y1-subfamily gene from an agnathan, the Europeanriver lamprey - A potential ancestral gene

We report here the isolation and functional expression of a neuropeptide Y (NPY) receptor from the river lamprey, Lampetra fluviatilis. The receptor d isplays approximate to 50% aminoacid sequence identity to all previously cl oned Y1-subfamily receptors including Y1, Y4, and y6 and the teleost subtyp es Ya, Yb and Yc. Phylogenetic analyses point to a closer relationship with Y4 and Ya/b/c suggesting that the lamprey receptor could possibly represen t a pro-orthologue of some or all of those gnathostome receptors. Our resul ts support the notion that the Y1 subfamily increased in number by genome o r large-scale chromosome duplications, one of which may have taken place pr ior to the divergence of lampreys and gnathostomes whereas the second dupli cation probably occurred in the gnathostome lineage after this split. Funct ional expression of the lamprey receptor in a cell line facilitated specifi c binding of the three endogenous lamprey peptides NPY, peptide YY and pept ide MY with picomolar affinities. Binding studies with a large panel of NPY analogues revealed indiscriminate binding properties similar to those of a nother nonselective Y1-subfamily receptor, zebrafish Ya. RT-PCR detected re ceptor mRNA in the central nervous system as well as in several peripheral organs suggesting diverse functions. This lamprey receptor is evolutionaril y the most distant NPY receptor that clearly belongs to the Y1 subfamily as defined in mammals, which shows that subtypes Y2 and Y5 arose even earlier in evolution.