Tuesday, February 20, 2007
Studies of population genetics, evolution are an exercise in bad taste
Scientific studies of why foods such as Brussels sprouts and stout beer are horribly bitter-tasting to some people but palatable to others are shedding light on a number of questions, from the mechanisms of natural selection to understanding how our genes affect our dietary habits (see "Origins and Evolution of Human Diet").
Dr. Stephen Wooding, a population geneticist at UT Southwestern Medical Center in Dallas, studies how slight variations in genes give rise to variations in traits among a given human population.
Part of Dr. Wooding's research focuses on variations in the genes responsible for bitter-taste receptors, tiny receptacles on the tongue that intercept harsh-tasting chemicals from food. Each of these genes comes in several forms, and the forms you carry help determine how you perceive bitter-tasting compounds.
The ability to taste or not taste bitter foods might have played a role in human evolution and may today account for such health-related behaviors as smoking and vegetable consumption, Dr. Wooding said. He presented an overview of his research on the bitter-taste receptor in San Francisco at the 2007 annual meeting of the American Association for the Advancement of Science (AAAS). The title of his talk is "Evolution: A Study in Bad Taste?" 
In the 1930s, scientists discovered differences in the ability of humans to taste a bitter synthetic compound called phenylthiocarbamide, or PTC, and they determined that the trait was controlled by genetics (the actual gene for PTC sensitivity was discovered in 2003). For PTC "tasters," even tiny concentrations of the compound are extremely bitter, while "nontasters" experience little or no taste to the same concentration of PTC.
"In some ways, bitter-taste sensitivity seems to be a trivial trait, but early geneticists recognized that this trait was special, for a variety of reasons," said Dr. Wooding, an assistant professor with UT Southwestern's Eugene McDermott Center for Human Growth and Development.
"Bitter-taste sensitivity is crucially important in protecting the human body from toxins in the environment. By enabling us to perceive noxious chemicals in potential foods - especially toxins used by plants to defend themselves against herbivores - bitter taste probably helped our early ancestors avoid poisoning," he said.
If that is the case, then why are both tasters and nontasters still present in the human population? Based on the rules of natural selection, shouldn't all of the nontasters have died off early in our evolution?
The answer is complex, Dr. Wooding said, noting that some things that taste bitter are used as medicine, such as compounds in certain tree barks that help protect against malaria.
He and his colleagues - Drs. Dennis Drayna and Un-kyung Kim at the National Institutes of Health, along with Drs. Lynn Jorde and Michael Barnshad at the University of Utah - analyzed the gene for PTC sensitivity for certain "signatures" of natural selection that would tell them how the gene has changed over time. They found very strong evidence that within humans, a process called "balancing natural selection" has taken place.
"This is a kind of natural selection that keeps two different forms of the same gene active in a population," Dr. Wooding said. "In this case they are the taster and the nontaster forms. In the absence of this type of natural selection, you would expect one form to dominate. That hasn't happened here because for some reason, there is not a strong advantage of one over the other. It's an unusual situation."
One hypothesis is that PTC nontasters can taste something that tasters can't.
"When we look at the nontaster form of the PTC receptor, it looks functional, so we think it probably responds to something," Dr. Wooding said. "One explanation could be that, long ago, it conferred some sort of protection from a different compound in these people."
Follow-up studies of variation in other bitter-taste receptor genes have revealed that different genes show different patterns of diversity. These might match up with other person-to-person differences in taste, Dr. Wooding said.
Regardless of the form of the PTC gene an individual carries, Dr. Wooding - who genetically is a taster - emphasized that taste preferences, upbringing and cultural issues clearly play very important roles in a person's diet.
"I personally like a little bit of bitter taste," he said.
Source (Adapted): University of Texas Southwestern Medical Center February 16, 2007
 See the 2005 Current Biology paper:
Evolution: A Study in Bad Taste?
Current Biology Volume 15, Issue 19, 11 October 2005, Pages R805-R807
Bitter tastes are among the most salient of life's experiences - who can forget one's first encounter with dandelion milk or a stout beer? Studies of the genes underlying these tastes are providing new perspectives on human origins and health.
Bitter-taste sensitivity, of course, begins on the tongue. Concentrated at the back of the tongue, on disc-like structures called circumvallate papillae, specialized bitter-taste receptor cells await contact with potentially bitter compounds. Upon exposure to an appropriate ligand, these receptor cells depolarize, generating a signal that is conveyed via the facial and glossopharyngeal nerves to the brain (Figure 1A). In principle, any mechanism that stimulates this neural pathway will lead to the sensation of bitter taste; however, recent studies have highlighted the importance of a small group of G-protein-coupled receptors encoded by the TAS2R (also called T2R) gene family.
In humans, this family includes roughly 25 functional genes and eight pseudogenes, each roughly a kilobase in length, found in three clusters on chromosomes 5, 7 and 12. The protein products of these genes are concentrated at the apex of bitter-taste receptor cells, near the taste pore, where they are positioned to bind bitter ligands as they wash past, dissolved in saliva (Figure 1A). Upon ligand binding, these receptors catalyze a series of reactions leading to the efflux of intracellular calcium, and the cascade of events leading to taste perception begins (Figure 1B).
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