The Evolutionary History of The Orexin/Allatotropin GPCR Family: from Placozoa and Cnidaria to Vertebrata

María Eugenia Alzugaray,Jorge Rafael Ronderos,María José Villalobos Sambucaro,María Cecilia Bruno

doi:10.1038/s41598-019-46712-9

Abstract

Peptidic messengers constitute a highly diversified group of intercellular messengers widely distributed in nature that regulate a great number of physiological processes in Metazoa. Being crucial for life, it 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 family of transmembrane molecules. GPCRs are also widely distributed in nature being present in metazoan, but also in Choanoflagellata and 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 was present in the common ancestor of Metazoa. Looking for the evolutionary history of this GPCRs we searched for corresponding sequences in public databases. Our results suggest that AT/Ox receptors were highly conserved along evolutionary process, and that they are characterized by the presence of the E/DRWYAI motif at the IC Loop 2. Phylogenetic analyses show that AT/Ox family of receptors reflects evolutionary relationships that agree with current phylogenetic understanding in Actinopterygii and Sauropsida, including also the largely discussed position of Testudines.

Highlights

Cell-cell communication is a basic principle in all organisms, necessary to facilitate the coordination and integration between cell populations, and with their environment
The Allatotropin/Orexin receptors ancestral signature. As it is described above, G-protein coupled receptors (GPCRs) are characterized by the presence of the E/DR motif associated to the TMIII (i.e. IC Loop 2)
After the analysis of 392 complete sequences, including N-terminal, C-terminal and the presence of 7 TM domains, we found that the motif E/DRWYI in the IC Loop 2 can be tracked from Chordata and Arthropoda, to Cnidaria and Placozoa

Summary

Introduction

Cell-cell communication is a basic principle in all organisms, necessary to facilitate the coordination and integration between cell populations, and with their environment. Integrative mechanisms as nervous and endocrine systems have appeared early along the evolutionary process and play a very important role, regulating many physiological processes in all animal phyla As it is known, these systems act by mean of messengers which can be basically grouped as hormones and neuromodulators. These systems act by mean of messengers which can be basically grouped as hormones and neuromodulators Among these chemical messengers, peptides constitute a highly diversified group of molecules widely distributed in nature, and regulate a great number of physiological processes in most groups of Metazoa, from cardiac and visceral muscle activity, to more complex phenomena as sleep-wakefulness, and appetite. The Rhodopsin family seems to be the most widely distributed in Metazoa and it is characterized by the existence of a E/DR motif associated to the third transmembrane domain (TM III) (i.e. IC Loop 2), which seems to be relevant for the transmission of the message, facilitating the activity of the associated G-proteins[13,14]

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Results

Conclusion