Background. Olfactory Receptors (ORs) form the largest multigene family in vertebrates. Their evolution and their expansion in the vertebrate genomes was the subject of many studies. In this paper we apply a motif-based approach to this problem in order to uncover evolutionary characteristics. Results. We extract deterministic motifs from ORs belonging to ten species using the MEX (Motif Extraction) algorithm, thus defining Common Peptides (CPs) characteristic to ORs. We identify species-specific CPs and show that their relative abundance is high only in fish and frog, suggesting relevance to water-soluble odorants. We estimate the origins of CPs according to the tree of life and track the gains and losses of CPs through evolution. We identify major CP gain in tetrapods and major losses in reptiles. Although the number of human ORs is less than half of the number of ORs in other mammals, the fraction of lost CPs is only 11%. By examining the positions of CPs along the OR sequence, we find two regions that expanded only in tetrapods. Using CPs we are able to establish remote homology relations between ORs and non-OR GPCRs. Selecting CPs according to their evolutionary age, we bicluster ORs and CPs for each species. Clean biclustering emerges when using relatively novel CPs. Evolutionary age is used to track the history of CP acquisition in the collection of mammalian OR families within HORDE (Human Olfactory Receptor Data Explorer). Conclusion. The CP method provides a novel perspective that reveals interesting traits in the evolution of olfactory receptors. It is consistent with previous knowledge, and provides finer details. Using available phylogenetic trees, evolution can be rephrased in terms of CP origins.
Gottlieb, A., Olender, T., Lancet, D., & Horn, D. (2009). Common peptides shed light on evolution of Olfactory Receptors. BMC Evolutionary Biology, 9(1). https://doi.org/10.1186/1471-2148-9-91