A unified nomenclature for vertebrate olfactory receptors

Abstract

Background 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. Results 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. Conclusions 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.

Decoding the olfactory map: targeted transcriptomics link olfactory sensory neurons to glomeruli

“…We further examined this relationship by comparing ORs above the 40% (family level ORs), 60% (subfamily level ORs) and 80% (highly similar, used to define OR orthologs) protein identity thresholds (48,49) using the pairwise alignment score thresholds 993 and 1337 respectively. Comparisons between family (567-993), subfamily (993-1337), and highly similar ORs (>1337) revealed similar results among the Class II ORs (Fig.…”

The Multilocus Multispecies Coalescent: A Flexible New Model of Gene Family Evolution

“…However, even in mammals, studies of closely related species have demonstrated the potential importance of ILS when short time frames are considered (Hobolth et al, 2011;Kutschera et al, 2014), suggesting that, as larger and larger data sets are generated and analysed, the pertinence of MLMSC should increase. Similarly, the modelling of genetic linkage between duplicates might be superfluous when relatively small and ancient gene families are considered, but should be crucial for the analyses of large and dynamic gene families, such as venom toxins (Fry et al, 2009) or olfactive receptors (Niimura et al, 2014), in which paralogous gene copies are often organized in clusters across the genome (Olender et al, 2020).…”

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“…[23,25] Species with a well-developed sense of olfaction, such as rats, have about 1400 olfactory receptor (OR) genes, whereas other mammals have fewer OR genes (cows 1000; dogs 800) but have a more extensive olfactory epithelium. [27][28][29][30] Humans have approximately 350 OR genes but have a dense network of receptors within the olfactory bulb. [29][30][31] Olfactory pathways arise in the two olfactory regions of the nasal cavity which contains receptor neurons, supporting cells, basal cells and microvillus cells.…”

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