The human olfactory receptor gene family

Abstract

Humans perceive an immense variety of chemicals as having distinct odors. Odor perception initiates in the nose, where odorants are detected by a large family of olfactory receptors (ORs). ORs have diverse protein sequences but can be assigned to subfamilies on the basis of sequence relationships. Members of the same subfamily have related sequences and are likely to recognize structurally related odorants. To gain insight into the mechanisms underlying odor perception, we analyzed the human OR gene family. By searching the human genome database, we identified 339 intact OR genes and 297 OR pseudogenes. Determination of their genomic locations showed that OR genes are unevenly distributed among 51 different loci on 21 human chromosomes. Sequence comparisons showed that the human OR family is composed of 172 subfamilies. Types of odorant structures that may be recognized by some subfamilies were predicted by identifying subfamilies that contain ORs with known odor ligands or human homologs of such ORs. Analysis of the chromosomal locations of members of each OR subfamily revealed that most subfamilies are encoded by a single chromosomal locus. Moreover, many loci encode only one or a few subfamilies, suggesting that different parts of the genome may, to some extent, be involved in the detection of different types of odorant structural motifs.

Fig. 2.

Phylogenetic tree of sequence relationships among ORs. This tree compares the 339 members of the human OR family, 23 rodent ORs of known function, and 28 fish ORs. Green branches represent fish ORs, and red branches represent human and rodent ORs with known odorant specificities. Odorants detected are indicated near the tip of each red branch. The majority of human homologs of rodent ORs for aliphatic odorants are located in one distinct branch of the tree. This branch (shaded in gray) also contains all of the fish ORs, suggesting a distant evolutionary relationship between receptors for aliphatic odorants and fish ORs.

Fig. 1.

Chromosome locations of human OR genes. Six hundred thirty OR genes were localized to 51 different chromosomal loci distributed over 21 human chromosomes. OR loci containing one or more intact OR genes are indicated in red; loci containing only pseudogenes are indicated in green. The cytogenetic position of each locus is shown on the left, and its distance in megabases from the tip of the small arm of the chromosome is shown on the right (chromosome-Mb). The number of OR genes at each locus is indicated in parentheses, and the number of OR genes on each chromosome is indicated below. Most human homologs of rodent ORs for n-aliphatic odorants are found at a single locus, chromosome 11p15.