Olfactory Receptors


The sense of smell is mediated by olfactory receptors belonging to the seven‐transmembrane G‐protein‐coupled receptor superfamily. They are expressed at the surface of the cilia of olfactory sensory neurons that emerge in the olfactory epithelium of the nasal cavity, and for some of them in mature spermatozoa. The specific binding of odorant ligands initiates signals transmitted to the central nervous system through different relays, allowing an individual to identify precisely a particular odour. In mammals, olfactory receptors are encoded by a large multigene family of about 1000 members whose evolution of the number of functional genes is related to species‐specific olfactory needs and to olfactory ability.

Keywords: sense of smell; multigene family; gene clusters; gene expression; tissue specificity

Figure 1.

Functional anatomy and structure of the olfactory system. (a) Sagittal view of a human head. The main olfactory epithelium (MOE) is circled together with the cribriform plate (bone) and the olfactory bulb. (b) The olfactory neuroepithelium is a tissue consisting of three cell types: olfactory sensory neurons (OSN, neuronal cell type), supporting cells and basal cells (stem cells) from which OSNs are generated. The cells of the MOE send their unbranched axons to target in the glomeruli of the (OB). Each OSN expresses only one olfactory receptor (OR) and the axons from all cells expressing that particular OR converge on to two glomeruli in the OB. Mitral axons leaving the OB project widely to higher brain structures. (c) Olfactory signal transduction pathway in higher vertebrates. The odorant interacts with the OR, resulting in G‐protein activation, stimulation of adenyl cyclase activity, opening of a cyclic nucleotide gated channel by elevated cAMP levels, influx of cations and depolarization generating an electrical signal that can be transmitted to the brain. Adapted from Firestein S (2001) How the olfactory system makes sense of scents. Nature 413: 211–218 and Mombaerts P (2001) How smell develops. Nature Neuroscience 4: 1192–1198.

Figure 2.

Schematic diagram of the OR protein structure. The membrane is represented as a shaded rectangle and the seven transmembrane domains (TM1–TM7) are indicated. The main conserved motifs as cited in the text are indicated, as well as the seven cysteine residues and the extracellular disulfide bonds. EC: extracellular; IC: intracellular.

Figure 3.

Evolution of the olfactory gene repertoire in mammals. The schematic phylogenetic tree shows the time scale of separation of the different clades in million years (MYA). On the right side is indicated the number of functional OR genes in the different species, showing that catarrhines present the highest degree of decimation of the olfactory system whereas mouse and dog have the highest count of functional OR genes.

Figure 4.

Chromosomal locations of the human OR gene repertoire. OR clusters are indicated on the right of each chromosome: 12/21, 1@155, means the cluster at 155 Mb from the p tip of chromosome 1 and containing 12 potentially functional genes (uninterrupted ORF) among a total of 21 genes. The names of the main clusters are indicated in bold (1@255, etc.) and the positions of the three ancestral clusters including 11@4 that contains all the fish‐like class I human ORs are boxed. Singletons are indicated by arrows on the left and additional chromosomal localizations determined by fluoresence in situ hybridization are indicated by open triangles. More than a half of the OR loci lie in telomeric and pericentromeric regions. Clustering of segments of diverse origin seems to occur near pericentromeric and subtelomeric regions. Regions near the chromosome tips are known to be gene rich and recombigenic. This nonrandom distribution of the OR gene repertoire could have arisen through frequent duplications (regional), transpositions, exchange of subtelomeric regions and pericentric inversions. Adapted from Rouquier S, Taviaux S, Trask B et al. Nature Genetics 18: 243–250 and Glusman et al. .

Figure 5.

Generation of the class II OR multigene family in the human genome. The filiation of the clusters is based on sequence comparisons. Clusters are named according to the nomenclature ‘chromosome@Mb coordinate’. The ancestral clusters are double boxed. The putative class I (11@4)®class II (11@52) initial duplication is indicated by an arrowed dashed line. The class II repertoire originated from the ancestral duplication 11@52®1@255 (bold arrow). Cluster 1@255 duplicated in multiple chromosomal locations (boxes on the right side) is followed by further duplications leading to the present OR gene repertoire. Intra‐ and interchromosomal duplication periods are indicated at the bottom. Adapted from Glusman et al. .



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Further Reading

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Trask B, Massa H, Brand‐Arpon V et al. (1998) Large multi‐chromosomal duplications encompass many members of the olfactory receptor gene family in the human genome. Human Molecular Genetics 7: 2007–2020.

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Giorgi, Dominique, Gaillard, Isabelle, and Rouquier, Sylvie(Jul 2007) Olfactory Receptors. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005666.pub2]