Neuropeptides and neuropeptide receptors in the Drosophila melanogaster genome

Recent genetic analyses in worms, flies, and mammals illustrate the importa nce of bioactive peptides in controlling numerous complex behaviors, such a s feeding and circadian locomotion. To pursue a comprehensive genetic analy sis of bioactive peptide signaling, we have scanned the recently completed Drosophila genome sequence for G protein-coupled receptors sensitive to bio active peptides (peptide GPCRs). Here we describe 44 genes that represent t he vast majority, and perhaps all, of the peptide GPCRs encoded in the fly genome. We also scanned for genes encoding potential ligands and describe 2 2 bioactive peptide precursors. At least 32 Drosophila peptide receptors ap pear to have evolved from common ancestors of 15 monophyletic vertebrate GP CR subgroups (e.g., the ancestral gastrin/ cholecystokinin receptor). Six p airs of receptors are paralogs, representing recent gene duplications. Toge ther, these Findings shed light on the evolutionary history of peptide GPCR s, and they provide a template for physiological and genetic analyses of pe ptide signaling in Drosophila.