A unified nomenclature for vertebrate olfactory receptors

Olfactory receptors (ORs) are G protein-coupled receptors with a crucial role in odor detection. A typical mammalian genome harbors ~ 1000 OR genes and pseudogenes; however, different gene duplication/deletion events have occurred in each species, resulting in complex orthology relationships. While the human OR nomenclature is widely accepted and based on phylogenetic classification into 18 families and further into subfamilies, for other mammals different and multiple nomenclature systems are currently in use, thus concealing important evolutionary and functional insights.

Here, we describe the Mutual Maximum Similarity (MMS) algorithm, a systematic classifier for assigning a human-centric nomenclature to any OR gene based on inter-species hierarchical pairwise similarities. MMS was applied to the OR repertoires of seven mammals and zebrafish. Altogether, we assigned symbols to 10,249 ORs. This nomenclature is supported by both phylogenetic and synteny analyses. The availability of a unified nomenclature provides a framework for diverse studies, where textual symbol comparison allows immediate identification of potential ortholog groups as well as species-specific expansions/deletions; for example, Or52e5 and Or52e5b represent a rat-specific duplication of OR52E5. Another example is the complete absence of OR subfamily OR6Z among primate OR symbols. In other mammals, OR6Z members are located in one genomic cluster, suggesting a large deletion in the great ape lineage. An additional 14 mammalian OR subfamilies are missing from the primate genomes. While in chimpanzee 87% of the symbols were identical to human symbols, this number decreased to ~ 50% in dog and cow and to ~ 30% in rodents, reflecting the adaptive changes of the OR gene superfamily across diverse ecological niches. Application of the proposed nomenclature to zebrafish revealed similarity to mammalian ORs that could not be detected from the current zebrafish olfactory receptor gene nomenclature.

We have consolidated a unified standard nomenclature system for the vertebrate OR superfamily. The new nomenclature system will be applied to cow, horse, dog and chimpanzee by the Vertebrate Gene Nomenclature Committee and its implementation is currently under consideration by other relevant species-specific nomenclature committees.