H

Pyriform and entorhinal cortex (primary olfactory cortex)

Odor molecules

Cilia of olfactory knob

Figure 13-1. Vertebrate (human) olfactory system showing olfactory epithelium, olfactory bulb of the brain and the pathway of olfactory neurons to the olfactory regions of the brain.

Olfactory bulb

Olfactory bulb neurons

Cribriform plate of ethmoid bone

Olfactory receptor cell

Supporting cells

Mucus layer

Odor molecules

Cilia of olfactory knob

Figure 13-1. Vertebrate (human) olfactory system showing olfactory epithelium, olfactory bulb of the brain and the pathway of olfactory neurons to the olfactory regions of the brain.

OR genes are the largest subset of this gene family and comprise about 3-4 percent of the entire genomes of some species (see Crasto et al. 2003; Crasto et al. 2002; Crasto et al. 2001; Skoufos et al. 1999). Like the number of ONs, the number of OR genes reflects the importance of olfaction and varies greatly among species. For example, there are about 1,000 in the rat, which exceeds their number of immunoglobulin and T cell receptor genes combined (Mombaerts 2001; 2001). Among vertebrates, the number of OR genes varies considerably and in interesting ways that can be related to function. Some of the genes have been mutated to pseudogenes, which may relate to sloppy copying during meiosis of tandemly repeated genes—the same process that generates the useful variety of ORs—but may also be affected by selection. Birds typically have relatively few OR genes, but this varies among species. Fish have about 100 OR genes. Primates have roughly the same number of OR genes as other mammals (about 1000 in humans); however, among species that have been studied, about 60 percent of primate OR genes are pseudogenes; a typical human may have around 350 functional OR genes (Crasto, Singer et al. 2001; Glusman et al. 2001; Mombaerts 2001; Sosinsky et al. 2000). Interestingly, New World monkeys have few OR pseudogenes (Rouquier et al. 2000).

As shown below in Figure 13-4, ORs are distributed on almost all chromosomes in both mouse and human, and the pseudogenes have roughly similar proportional distribution. The high fraction of pseudogenes in humans thus is likely to have to do with selection or function, since the majority of mouse genes are still functional yet presumably the duplication and mutation processes are similar (but see some further thoughts at the end of this chapter).

Extracellular

Extracellular

Intracellular A

Figure 13-2. Odorant receptors and related genes. (A) Schematic of a seven transmembrane (7TMR) olfactory receptor molecule showing amino acids, specifically for receptor M71 in the mouse. The most highly conserved residues are shown in white and black, and the most variable are in shades of gray, presumably indicating the most important sites for odorant specificity. (See Firestein 2001); (B) General phylogenetic (gene sequence) relationships among major classes of chemoreceptors. The approximate numbers of genes in these classes are indicated (modified after Firestein 2001).

Intracellular A

Figure 13-2. Odorant receptors and related genes. (A) Schematic of a seven transmembrane (7TMR) olfactory receptor molecule showing amino acids, specifically for receptor M71 in the mouse. The most highly conserved residues are shown in white and black, and the most variable are in shades of gray, presumably indicating the most important sites for odorant specificity. (See Firestein 2001); (B) General phylogenetic (gene sequence) relationships among major classes of chemoreceptors. The approximate numbers of genes in these classes are indicated (modified after Firestein 2001).

Fish OR -100

Mammal ORs -500 - 1,000 (olfactory receptors)

Bird ORs?

T2Rs? (taste receptors)

T1Rs -80

V2Rs-150 (vomeronasal receptors)

V1Rs-150

DOR 61 (Drosophila odor receptors )

DGR-60 (Drosophila taste receptors)

Other GPCRs -400 in mammal

Figure 13-2. Continued

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