The sense of smell: genomics of vertebrate odorant receptors

Olfactory receptor (OR) proteins interact with odorant molecules in the nose, initiating a neuronal response that triggers the perception of a smell. The OR family is one of the largest known mammalian gene families, with around 900 genes in human and 1500 in mouse. After discounting pseudogenes, the functional repertoire in mouse is more than three times larger than that of human. OR genes encode G-protein-coupled receptors containing seven transmembrane domains. ORs are arranged in clusters of up to 100 genes dispersed in 40-100 genomic locations. Each neuron in the olfactory epithelium expresses only one allele of one OR gene. The mechanism of gene choice is still unknown, but must involve locus, gene, and allele selection. The gene family has expanded mainly by tandem duplications, many of which have occurred since the divergence of the rodent and primate lineages. Interchromosomal segmental duplications including OR genes have also occurred, but more commonly in the human than the mouse family. As a result, many human OR genes have several possible mouse orthologs, and vice versa. Sequence and copy number polymorphisms in OR genes have been described, which may account for interindividual differences in odorant detection thresholds.