June 2004

University of Utah Health Sciences Center

Natural selection at work in genetic variation to taste

Utah researchers find evidence at molecular level for PTC

SALT LAKE CITY - A genetic variation seen worldwide in which people either taste or do not taste a bitter, synthetic compound called PTC has been preserved by natural selection, University of Utah and National Institutes of Health researchers have reported.

Phenylthiocarbamide (PTC) is not found in nature, but the ability to taste it correlates strongly with the ability to taste other bitter substances that occur naturally, especially toxins. Eons ago, the ability to discern bitter tastes developed as an evolutionary mechanism to protect early humans from eating poisonous plants.

"We found evidence at the molecular level that natural selection has maintained the variation in the gene that allows us to taste or not taste PTC," said geneticist Stephen Wooding, Ph.D., corresponding author on the study and a post-doctoral fellow at the Eccles Institute of Human Genetics at the University of Utah School of Medicine.

Today, the ability to taste, or not taste, the compound influences what people eat and even whether they smoke cigarettes.

People who can taste PTC are less likely to eat cruciferous vegetables such as broccoli, according to Wooding, which could be a problem because these vegetables contain important nutrients. If the ability to discern bitter tastes discourages PTC tasters from eating broccoli, it also may have the advantage of dissuading them from inhaling the acrid smoke of cigarettes. "Among smokers, there seems to be an excess of PTC non-tasters," Wooding said. "So it seems that PTC tasters are less likely to smoke."

The researchers recently published their findings in the American Journal of Human Genetics.

Typically, over hundreds of thousands years, genetic drift takes place, a process in which gene frequencies and genetic traits change randomly within a population. Under that expectation, everybody either would be a PTC taster or non-taster by now. But worldwide the ratio has remained at roughly 75/25 between PTC tasters and non-tasters.

The U researchers found that two versions of the PTC allele (genes) are present worldwide, from America to Africa. After comparing thousands of genes, the researchers found that the presence of such divergent alleles is highly unusual. But the existence of two PTC alleles can be explained by evolutionary pressure to avoid the toxins that plants produce to defend themselves against herbivores.

Everybody carries two copies of the PTC taster gene, meaning any individual could carry two copies of the PTC taster allele, two of the non-taster allele, or one of each. "We hypothesize that people carrying one copy of each allele are able to taste a broader range of toxic, bitter compounds, and have an evolutionary advantage," Wooding said.

Last year, researchers at the National Institutes of Health and the University of Utah discovered the PTC gene and found that it comes in two major alleles. One allele encodes the receptor to bind PTC, and the other, which differs by three amino acids from the first, encodes a receptor that probably binds with different bitter compounds. Those researchers included the U of U medical school's Mark F. Leppert, Ph.D., professor and co-chair of the Department of Human Genetics, and Hilary Coon, Ph.D., associate professor of psychiatry.

The ability to taste or not taste PTC was discovered in 1930. An American chemist named Arthur Fox accidentally let loose a quantity of PTC in a laboratory and noticed that while some people could taste it, others could not. After that, it was long hypothesized that alleles were responsible for the ability to taste PTC, according to Wooding.

The PTC gene is only one of 24 bitter taste genes. Wooding and the others would like to research the remaining genes to make a stronger correlation to smoking and diet.

"I would like to know which genes contribute most to smoking tendencies," Wooding said.

Other authors of the latest study include: Lynn B. Jorde, Ph.D., professor of human genetics at the U of U School of Medicine; Michael J. Bamshad, M.D., associate professor of pediatrics, U of U School of Medicine; Un-kyung Kim and Jennifer Larsen, both of the National Institute of Deafness and Other Communication Disorders, National Institutes of Health.




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