THE EVOLUTIONARY HISTORY OF THE OREXIN/ALLATOTROPIN GPCR FAMILY: FROM PLACOZOA AND CNIDARIA TO VERTEBRATA

Cell-cell communication is a basic principle in all organisms, necessary to facilitate the coordination and integration between cell populations. These systems act by mean of chemical messengers. Peptides constitute a highly diversified group of intercellular messengers widely distributed in nature, and regulate a great number of physiological processes in Metazoa. Being crucial for life, it would seem that they have appeared in the ancestral group from which Metazoa evolved, and were highly conserved along the evolutionary process. Peptides act mainly through G-protein coupled receptors (GPCRs), a great family of transmembrane molecules. GPCRs are also widely distributed in nature being present not only in metazoan, but also in Choanoflagellata (unicellular eukariotes related with metazoans), and even in Fungi. Among GPCRs, the Allatotropin/Orexin (AT/Ox) family is particularly characterized by the presence of the DRW motif in the second intracellular loop (IC Loop 2), and seems to be present in Cnidaria, Placozoa and in Bilateria, suggesting that it also was present in the common ancestor of Metazoa. Looking for the evolutionary history of this GPCR family we searched in the GenBank for sequences corresponding to this family of receptors (i.e. seven transmembrane domain and the E/DRW motif at the second IC Loop 2). Our results show that AT/Ox receptors were highly conserved along evolutionary history of Metazoa, and that they might be defined by the presence of the E/DRWYAI motif at the level of IC Loop 2. Molecular phylogenetic analyses performed by Maximum Likelihood method suggest that AT/Ox family of receptors reflects evolutionary relationships that agree with current understanding of phylogenetic relationships in Actinopterygii and Sauropsida, including also the largely discussed position of Testudines.