Background: Vertebrate odorant receptors comprise at least three types of G protein-coupled receptors (GPCRs): the OR, VIR, and V2R/V2R-like receptors, the latter group belonging to the C family of GPCRs. These receptor families are thought to receive chemosensory information from a wide spectrum of odorant and pheromonal cues that influence critical animal behaviors such as feeding, reproduction and other social interactions. Results: Using genome database mining and other informatics approaches, we identified and characterized the repertoire of 54 intact V2R-like olfactory C family GPCRs in the zebrafish. Phylogenetic analysis - which also included a set of 34 C family GPCRs from fugu - places the fish olfactory receptors in three major groups, which are related to but clearly distinct from other C family GPCRs, including the calcium sensing receptor, metabotropic glutamate receptors, GABA-B receptor, TIR taste receptors, and the major group of V2R vomeronasal receptor families. Interestingly, an analysis of sequence conservation and selective pressure in the zebrafish receptors revealed the retention of a conserved sequence motif previously shown to be required for ligand binding in other amino acid receptors. Conclusion: Based on our findings, we propose that the repertoire of zebrafish olfactory C family GPCRs has evolved to allow the detection and discrimination of a spectrum of amino acid and/or amino acid-based compounds, which are potent olfactory cues in fish. Furthermore, as the major groups of fish receptors and mammalian V2R receptors appear to have diverged significantly from a common ancestral gene(s), these receptors likely mediate chemosensation of different classes of chemical structures by their respective organisms.
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