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Thursday, January 11, 2007

Olfactory Receptor Genes

The human genome contains 388 different olfactory receptor (OR) genes. These genes encode olfactory receptors, the molecules that detect odors [A Sense of Smell: Olfactory Receptors]. Our genome also has 414 olfactory receptor pseudogenes. These are stretches of DNA that resemble functional genes but they have accumulated mutations rendering them non-functional. In some cases, a single mutation has disrupted the open reading frame—these pseudogenes have recently evolved from functional genes. In most cases the olfactory receptor pseudogenes have multiple mutations, including extensive insertions and deletions, indicating that these pseudogene lost functionality millions of years ago.

None of the olfactory receptor genes have introns. This is a huge advantage because it is much easier to recognize functional genes and pseudogenes by scanning the genome.

The human genes and pseudogenes are clustered. Some clusters contain dozens of genes while others have only a few. There are 95 different clusters spread over all chromosomes except chromosome 20 and the Y chromosome. The first figure (below) is from a review by Niimura and Nei (2006). It shows the locations of the OR gene clusters. The vertical lines above the chromosome indicate the number of functional genes at that position—the taller the line the more genes. Lines below the chromosome indicate pseudogenes at that position.

A phylogenetic tree of the 388 functional OR genes reveals two main classes. All 57 class I genes are clustered together on chromosome 11. The class II genes can be subdivided into several subgroups labelled A to S in the figure below (Fig. 2 from Niimura and Nei (2006)). Several clusters are shown in order to illustrate the fact that genes of the same subclass tend to cluster together. Large letters indicate functional genes and small letters indicate related pseudogenes. Genes below the line are transcribed in the opposite direction from those above the line. (X identifies unclassified genes.)

Adjacent, closely related genes that are transcribed in the same direction are said to be tandemly duplicated, indicating that they probably arose by gene duplication. For example, most of the subclass A genes in cluster 11.11 probably resulted from repeated duplication of single A-type gene at that site.

The mouse genome contains 1037 functional genes and 354 pseudogenes in 69 clusters. Almost all of the clusters map to related clusters in the human genome. If we look at the relationship between the clusters on human chromosome 11 (Hs11) and mouse chromosome 2 Mm2), we see that the mouse cluster is larger and parts of it have been split up into four different clusters in humans. Nevertheless, the general order of genes is similar in mice and humans. There are more mouse OR genes, as expected. It has long been known that genes on human chromosome 11 are related to genes on mouse chromosome 2. (The figure is from Niimura and Nei (2006)).

How did this large gene family evolve? It seems clear that the common ancestor of mice and humans must have had many OR genes. It appears that the number of genes has probably changed considerably in one, or both, lineages. Why, and how, do some genes become inactivated? Is evolution of gene families due to natural selection or someting else? See "The Evolution of the Olfactory Receptor Gene Family" in tomorrow's posting.)

Niimura Y. and Nei M. (2006) Evolutionary dynamics of olfactory and other chemosensory receptor genes in vertebrates. J. Hum. Genet. 51:505-17


RPM said...

I like this figure on the frequency of types OR genes found in different vertebrates.

Larry Moran said...

Be patient. We'll get to it tomorrow. (It's in the Niimura and Nei paper that I'm discussing.) I need to set up the evolution of these genes first before we can understand the figure. It supports Nei's favorite mechanism of evolution of gene families.

Mihai said...

can you write some genes that are responsabile for pecetion of smell