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Stanford Report, February 26, 2003

Bitter or sweet? Researcher spits out gene linked to taste sensation

By AMY ADAMS

Hate broccoli? Take heart. Researchers have discovered a single gene that helps explain why some people love their leafy greens while others simply can’t bear the bitter taste.

More than 10 million American high-school and college students have experienced this bitter taste through a biological taste test that has become a staple of science classes. Those who recoil in horror upon chewing on a piece of paper soaked in phenylthiocarbamide, or PTC, are called tasters while those who chomp on the paper without gagging are called nontasters.

Now, researchers at the medical center have helped identify the gene responsible for the ability to taste PTC and found variations within the gene that lead some people to be tasters and others to be nontasters.

Their findings appear in the Feb. 22 issue of the journal Science.

"This is exciting because the ability to taste PTC is one of the oldest and most studied traits in humans," said Neil Risch, PhD, professor of genetics, statistics, and health research and policy, and a senior author on the study.

In addition to explaining a longtime high-school experiment, finding the gene for tasting PTC could help explain research at other labs that has linked a person’s taster status to his or her food preferences and overall health.

In one series of studies, tasters were more sensitive to spicy and sweet foods and found fatty foods less appealing. They tended to avoid broccoli and grapefruit juice, found spicy food painful and shunned fat. These preferences made themselves visible in older women. Tasters tended to be thinner and had more "good" (HDL or high density lipoproteins) cholesterol than nontasters.

Researchers had previously narrowed the ability to taste PROP, a chemical similar to PTC, to a small region of chromosome 7.

Risch and his colleagues followed up on this work by searching the genome for variations that related to whether a person could taste PTC. Like the previous studies, they connected taster status with a region of chromosome 7.

To pin down the exact location of the gene, the team sequenced all taste- and odor-detecting genes in this region. Risch and graduate student Eric Jorgenson then statistically analyzed the data and found one gene with a variation that was strongly associated with taster status. This gene turns out to be very similar to other genes whose proteins detect bitter tastes.

When the researchers sequenced the PTC gene in all the people in their sample, they found three genetic changes that related to whether the people were tasters. Each of these genetic changes caused a molecular switch in the protein made by the gene.

In the most common form of the gene, the protein has an amino acid designated "A" at the first variable location, an amino acid designated "V" at the second location and one designated "I" at the third location.

Researchers called this form of the gene AVI. The other common form of the gene was designated PAV for the sequence of amino acids in its variable regions. Least common was a sequence designated AAV.

It turns out that those people who inherit the AVI version of the gene from both parents don’t taste PTC, whereas those who inherit two PAV genes are extremely sensitive to the bitter chemical.

Those who inherit one of each gene version can taste PTC, but not as strongly as those with two copies of PAV. The AAV version is less clear-cut. Those who inherited AAV from one parent and PAV from the other are tasters, whereas those who inherit AAV with AVI may be somewhat able to taste PTC.

Risch pointed out that the PTC gene alone doesn’t account for the full range of how well a person can taste PTC. "The gene we identified explains 60 percent to 70 percent of the variability between people," he said. What’s more, he pointed out that the range of tasters and nontasters is more like a continuum than a sharp divide: some tasters seem to taste more than others. What makes up the rest of the story is still unknown, he said.

In addition to giving those who hate broccoli and grapefruit juice a biological excuse to be picky, Risch said this work could lend insight to human genetic diversity.

In Risch’s analysis, Caucasians had all three variations of the PTC gene, but people from eastern or western Asia only had the AVI or PAV variations. Native Americans are almost all tasters, containing almost exclusively the PAV gene variation.

What’s particularly interesting is that people of African descent had additional variations that Risch didn’t find in other populations. He said according to one explanation of human diversity, people left Africa and traveled across Europe and over to the Americas. Those who left Africa may not have taken all the PTC variants with them.

"What we see here really parallels what has been seen in other population surveys," Risch said. "Variation diminishes as you move farther from Africa."

Other institutions involved in this research include the National Institute on Deafness and Other Communication Disorders (National Institutes of Health) and the University of Utah Medical Center.




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