The mouse olfactory receptor gene family

Abstract

In mammals, odor detection in the nose is mediated by a diverse family of olfactory receptors (ORs), which are used combinatorially to detect different odorants and encode their identities. The OR family can be divided into subfamilies whose members are highly related and are likely to recognize structurally related odorants. To gain further insight into the mechanisms underlying odor detection, we analyzed the mouse OR gene family. Exhaustive searches of a mouse genome database identified 913 intact OR genes and 296 OR pseudogenes. These genes were localized to 51 different loci on 17 chromosomes. Sequence comparisons showed that the mouse OR family contains 241 subfamilies. Subfamily sizes vary extensively, suggesting that some classes of odorants may be more easily detected or discriminated than others. Determination of subfamilies that contain ORs with identified ligands allowed tentative functional predictions for 19 subfamilies. Analysis of the chromosomal locations of members of each subfamily showed that many OR gene loci encode only one or a few subfamilies. Furthermore, most subfamilies are encoded by a single locus, suggesting that different loci may encode receptors for different types of odorant structural features. Comparison of human and mouse OR subfamilies showed that the two species have many, but not all, subfamilies in common. However, mouse subfamilies are usually larger than their human counterparts. This finding suggests that humans and mice recognize many of the same odorant structural motifs, but mice may be superior in odor sensitivity and discrimination.

Fig. 1.

Chromosome locations of mouse OR genes. Mouse OR genes were mapped to 51 loci on 17 chromosomes. OR loci are indicated in red, except for those with no intact OR genes, which are shown in green. The position of each locus (blue) is shown on the left in Mb from the centromere (top). The number of intact OR genes and OR pseudogenes and the number of subfamilies encoded are indicated on the right for each locus and above for each chromosome [intact genes (subfamilies)/pseudogenes].

Fig. 2.

Comparison of mouse and human ORs. An unrooted phylogenetic tree showing protein sequence relationships among representatives of all mouse (green) and human (red) OR subfamilies. One member of each subfamily was used (435 sequences) in addition to 25 ORs with known ligands (black). Mouse and human ORs are interspersed throughout the tree, indicating that the OR repertoires of the two species are similar. Many ORs that detect aliphatic odorants (S19-S86) are located in a distinct branch, which is shaded in gray.

Fig. 3.

Sizes of OR subfamilies in human vs. mouse. Each human (red) and mouse (green) subfamily is indicated by a horizontal bar. The number of ORs per subfamily is shown on the x axis. The 150 subfamilies shared by the two species are indicated by pairs of red and green bars. Most of the shared subfamilies have more members in mouse than in human. Subfamilies unique to mouse or human, or found in both species, are indicated on the left.