Genetics Play A Large Part In Olfaction
December 14, 2013

Sense Of Smell Starts At The Genetic Level

April Flowers for - Your Universe Online

People react differently to the same smells. Something that smells wonderful to you could be offensive to your friend, but why this is so has been a mystery. The answer could lie in your genetic makeup, says a research team from Duke University. Their findings, published in the early online edition of Nature Neuroscience, reveal that a difference at the smallest level of DNA — one amino acid on one gene — determines whether or not you like a smell.

Approximately 400 genes code for the receptors in our noses, and according to the 1000 Genomes Project, there are more than 900,000 variations of those genes. How we smell odors is determined by sensors controlled by these receptors. A suite of receptors in the nose will be activated by a given odor, creating a specific signal for the brain.

According to Hiroaki Matsunami, Ph.D., associate professor of molecular genetics and microbiology at the Duke University School of Medicine, the receptors do not work the same for all of us. Matsunami, who is also a member of the Neurobiology Graduate Program and the Duke Institute for Brain Sciences, explained that there should be at least a 30 percent difference when comparing the receptors in any two people.

"There are many cases when you say you like the way something smells and other people don't. That's very common," Matsunami said. But what the researchers found is that no two people smell things the same way. "We found that individuals can be very different at the receptor levels, meaning that when we smell something, the receptors that are activated can be very different (from one person to the next) depending on your genome."

The study did not investigate the promoter regions of the genes, which are highly variable, or gene copy number variation, which is very high in odor receptors. Matsunami said that this means the 30 percent figure for the difference between individuals is probably conservative.

Prior studies have identified the genes that encode for odor receptors, however, it has remained a mystery how the receptors are activated. Matsunami's team cloned more than 500 receptors each from 20 people that had slight variations of only one or two amino acids and systematically exposed them to odor molecules that might excite the receptors.

They exposed the receptors to a very small concentration—1,10 or 100 micromoles—of 73 odorants, such as vanillin or guaiacol, allowing them to identify 27 receptors that had a significant response to at least one odorant. This doubles the number of known odorant-activated receptors, bringing the total to 40.

The research could have a big impact for the flavors, fragrance, and food industries, Matsunami added.

"These manufacturers all want to know a rational way to produce new chemicals of interest, whether it's a new perfume or new-flavored ingredient, and right now there's no scientific basis for doing that," he said. "To do that, we need to know which receptors are being activated by certain chemicals and the consequences of those activations in terms of how we feel and smell."