BITTER OR SWEET?

STANFORD RESEARCH SPITS OUT GENE LINKED TO TASTE

SENSATION
2/20/03 News Release
STANFORD, Calif. 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 Stanford University 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 their 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 that 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. They 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.