Olfactory genes control complex system for smelling odors

Barbara Trask

When we breathe in an odorant, molecules travel through our nasal passages to our olfactory neuroepithelium, our smelling center, where they bind with olfactory receptors. These olfactory receptors are located on sensory neurons, which emit an electrical impulse that informs the brain. Considering that we can discern over 10,000 distinct odors and that we have an estimated 1,000 olfactory receptor genes, the complexity of our sense of smell is vast.

Dr. Barbara Trask, a UW School of Medicine professor of molecular biotechnology, suggests that as much as 0.1 percent of the entire human genome is made up of DNA that has duplicated over evolutionary time to make this large family of olfactory receptor genes (ORs). In other words, she says: “That is a lot of DNA to work with.”

Using fluorescence in situ hybridization (FISH) techniques, in which researchers deposit and detect a fluorescent signal at the sites of cloned genes, Trask and colleagues have located OR genes in over 40 locations of the genome, often near the ends, which tend to be more in “flux” than other areas.

How just one OR gene is “turned on” so that each sensory cell carries just one olfactory receptor — one out of the estimated 1,000 different olfactory receptors that are expressed our nose — is an area researchers are trying to learn more about.

Trask will discuss these efforts in a Science in Medicine Lecture on Thursday, April 29 from noon to 1 p.m., in room T-625 of the Health Sciences Center. Her lecture is titled “The Genomic Organization of the Olfactory Receptor Gene Family.”

Trask and colleagues recently discovered that some OR genes are expressed in different numbers in different people, which is very unusual. Most known genes are present in two copies, one maternal and one paternal, and the same number of copies are used in us all.

The finding that one individual may have 11 copies of a particular OR gene, while another has only seven, and that these can be located in different areas of the genome, will make such work as sequencing the human genome a much more difficult task. The Human Genome Project is established on the idea that a single map of the human genome will represent us all because the genetic differences that result in different hair, eyes or skin color are usually created by minor mutations of the same gene located in the same area of the chromosome.

“These data show that there are big structural differences between us, differences in the presence or absence of big blocks of DNA,” Trask said. “We’ve underestimated the complexity of the genome and the extent of its variability,” she said.

Also, a large number of the genes in the OR family have mutated and are no longer functional but appear to be sticking around in the genome, forming something like a genetic junk pile that researchers will have to sift through to uncover significant genes.

“We’ll need to look more closely at what functional consequences the unusual features of these OR genes have in human biology,” she said.

Trask received a B.S. in wildlife ecology and an M.S. degree from Purdue University in 1977 for biochemical and behavioral studies of a putative pheromone. She received a Ph.D. from the University of Leiden in Holland in 1985 for her flow cytometric analyses of chromosomes and nuclei.

Trask spent seven years as a staff scientist at the Lawrence Livermore National Laboratory in California before joining the Department of Molecular Biotechnology at the University of Washington in 1992. She serves on the National Institutes of Health Genome Study Section and the editorial boards of American Journal of Human Genetics, Chromosome Research, Genome Research, and Cytogenetics and Cell Genetics. ¶

Will Morton