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 olfactory bulb (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. Nature413: 211–218 and Mombaerts P (2001) How smell develops. Nature Neuroscience4: 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 Genetics18: 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. .



Araneda RC, Kini AD and Firestein S (2000) The molecular receptive range of an odorant receptor. Nature Neuroscience 3: 1248–1255.

Brand‐Arpon V, Rouquier S, Massa H et al. (1999) A genomic region encompassing a cluster of olfactory receptor genes and a myosin light chain kinase (MYLK) gene is duplicated on human chromosome regions 3q13–21 and 3p13. Genomics 56: 98–110.

Buck L and Axel R (1991) A novel multigene family may encode odorant receptors: a molecular basis for odor recognition. Cell 65: 175–187.

Chess A, Simon I, Cedar H and Axel R (1994) Allelic inactivation regulates olfactory receptor gene expression. Cell 78: 823–834.

Glusman G, Sosinsky A, Ben‐Asher E et al. (2000) Sequence, structure, and evolution of a complete human olfactory receptor gene cluster. Genomics 63: 227–245.

Glusman G, Yanai I, Rubin I and Lancet D (2001) The complete human olfactory subgenome. Genome Research 11: 685–702.

Krautwurst D, Yau K‐W and Reed R (1998) Identification of ligands for olfactory receptors by functional expression of a receptor library. Cell 95: 917–926.

Liberles S and Buck L (2006) A second class of chemosensory receptors in the olfactory epithelium. Nature 442: 645–650.

Lomvardas S, Barnea G, Pisapia D et al. (2006) Interchromosomal interactions and olfactory receptor choice. Cell 126: 403–413.

Mombaerts P (1999) Seven‐transmembrane proteins as odorant and chemosensory receptors. Science 286: 707–711.

Olender T, Fuchs T, Linhart C et al. (2004) The canine olfactory subgenome. Genomics 83: 361–372.

Quignon P, Kirkness E, Cadieu E et al. (2003) Comparison of the canine and human olfactory receptor gene repertoires. Genome Biology 4: R80.

Rodriguez I (2005) Remarkable diversity of mammalian pheromone receptor repertoires. Proceedings of the National Academy of Sciences of the USA 102: 6639–6640.

Rouquier S, Blancher A and Giorgi D (2000) The olfactory receptor gene repertoire in primates and mouse: evidence for reduction of the functional fraction in primates. Proceedings of the National Academy of Sciences of the USA 97: 2870–2874.

Rouquier S, Taviaux S, Trask B et al. (1998) Distribution of olfactory receptor genes in the human genome. Nature Genetics 18: 243–250.

Serizawa S, Miyamichi K, Nakatani H et al. (2003) Negative feedback regulation ensures the one receptor–one olfactory neuron rule in mouse. Science 302: 2088–2094.

Sodergren E, Weinstock GM, Davidson EH et al. (2006) The genome of the sea urchin Strongylocentrotus purpuratus. Science 314: 941–952.

Spehr M, Gisselmann G, Poplawski A et al. (2003) Identification of a testicular odorant receptor mediating human sperm chemotaxis. Science 299: 2054–2058.

Spehr M, Kelliher K, Li X et al. (2006) Essential role of the main olfactory system in social recognition of major histocompatibility complex peptide ligands. Journal of Neurosciences 26: 1961–1970.

Weizmann Institute. Database for the analysis of olfactory receptor gene and protein sequences http://bioinfo.weizmann.ac.il/HORDE/

Zhao H, Ivic L, Otaki J et al. (1998) Functional expression of a mammalian odorant receptor. Science 279: 237–242.

Further Reading

Asai H, Kasai H, Matsuda Y et al. (1996) Genomic structure and transcription of a murine odorant receptor gene: differential initiation of transcription in the olfactory and testicular cells. Biochemical and Biophysical Research Communications 221: 240–247.

Eisenbach M and Giojalas L (2006) Sperm guidance in mammals – an unpaved road to the egg. Nature Reviews Molecular Cell Biology 7: 276–285.

Gilad Y, Man O and Glusman G (2005) A comparison of the human and chimpanzee olfactory receptor gene repertoires. Genome Research 15: 224–230.

Hubbard TJ, Aken BL, Beal K et al. (2007) Ensembl 2007. Nucleic Acids Research 35(Database issue): D610–617.

Imai T, Suzuki M and Sakano H (2006) Odorant receptor‐derived cAMP signals direct axonal targeting. Science 314: 657–661.

Malnic B, Hirono J, Sato T and Buck LB (1999) Combinatorial receptor codes for odors. Cell 96: 713–723.

Malnic B, Godfrey PA and Buck LB (2004) The human olfactory receptor gene family. Proceedings of the National Academy of Sciences of the USA 101: 2584–2589.

Mombaerts P (2004) Genes and ligands for odorant, vomeronasal and taste receptors. Nature Reviews Neuroscience 5: 263–278.

Mombaerts P (2004) Odorant receptor gene choice in olfactory sensory neurons: the one receptor–one neuron hypothesis revisited. Current Opinions in Neurobiology 14: 31–36.

Quignon P, Giraud M, Rimbault M et al. (2005) The dog and rat olfactory receptor repertoires. Genome Biology 6: R83.

Spehr M, Schwane K, Heilmann S et al. (2004) Dual capacity of a human olfactory receptor. Current Biology 14: R832–R833.

Spehr M, Spehr J, Ukhanov K et al. (2006) Parallel processing of social signals by the mammalian main and accessory olfactory systems. Cellular and Molecular Life Sciences 63: 1476–1484.

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]