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Bitter is Bigger Than Just a Bad Taste in Your Mouth: How a Tiny Genetic Mutation is Helping Us Map Human Migration Out of Africa

Dennis Drayna
Dr. Dennis Drayna
For someone who studies things that are very small, Dennis Drayna thinks big. A seemingly run-of-the-mill discussion on the molecular underpinnings of bitter taste receptors can quickly veer into a story about the migrations of ancient peoples out of Africa 70 thousand years ago. Remarkably, we can learn about more than just tastebuds by trying to figure out why some people taste bitter and others don’t.

 

Taste receptors are located on specialized taste cells that bundle together within a taste bud on the surface of the human tongue. Taste receptors are able to sense five basic tastes: sweet, sour, bitter, salty, and umami, which is the savory flavor we get from foods rich in glutamate, such as meat and cheese. The ability to taste bitter may be the most important, says Dr. Drayna, who is chief of the Section on Systems Biology of Communication Disorders in the Laboratory of Molecular Genetics at the NIDCD. “The reason why we have a sense of bitter taste is to protect us from ingesting toxic substances, primarily in plants.”

Variation in the ability to taste bitter substances was discovered by accident in the 1930s when a DuPont chemist found that crystals of a substance called PTC (phenylthiocarbamide) tasted very bitter to some people but were tasteless to others. Population studies of the numbers of tasters versus non-tasters revealed that about 75 percent of us perceive PTC as very bitter, while the remaining 25 percent don’t. This informed a body of research that initially proposed that non-tasters inherited the trait as a recessive gene.

As it turns out, it wasn’t that simple. In 2003, Dr. Drayna and his team of researchers at the NIDCD identified three variants in a gene that eventually came to be called TAS2R38. If you have two copies of this variant form, you are a non-taster. If you don’t, you would find PTC very bitter indeed.

However, the TAS2R38 gene had even more to tell us than just whether or not we are able to taste something as bitter. In studying the genetic code of TAS2R38, Dr. Drayna and his colleagues found that the non-taster variant was what scientists call a “founder gene,” in which the genetic variation is derived from a single ancestral individual, long lost in prehistory. They can tell this because the TAS2R38 variant is embedded in a larger piece of DNA that is identical in everyone else carrying that variant, in addition to the founder of a population. This suggests that all non-tasters, everywhere in the world, descended from the same individual.

The team then performed a bit of genetic detective work. Measuring the length of the stretch of DNA that surrounds the founder variant—the shorter it is, the older the gene—and determining who currently carries the founder variant and where they live, Dr. Drayna and his colleagues could estimate the approximate date at which the variant first appeared. They then followed its migration through time and space to trace the history of human migration out of Africa and into the rest of the world.

“Perhaps as few as a couple hundred people left Africa 70 thousand years ago and they spread rapidly,” says Dr. Drayna. “At least one of them had to have the TAS2R38 mutation, and in the course of thousands of years, the mutation was passed on over and over again,” and thus the non-taster form of the TAS2R38 gene became common worldwide.

Looking at patterns of variation in the TAS2R38 gene among Africans, Asians, and Europeans today reveals that the most variations for the PTC gene—seven different forms—were found in sub-Saharan Africa. Only two of these, called the major taster form and the major non-taster form, exist in high numbers in populations outside of sub-Saharan Africa. These appear to be the two major forms that emerged from Africa and rapidly spread around the world.

As much as taste research can tell us about human migration, it can tell us even more about the nature of food preferences and it has a key role to play in advances in other fields of study. “Half of the mechanics of taste is genetic, the other half is a combination of other factors,” says Dr. Drayna. “Now we’ve got our hands on half of it—the genetic part. Gaining an understanding of the underlying genetic differences in taste perception, we can help untangle all sorts of other studies, not only for food preferences and consumption, but also studies that have to do with nutrition research, obesity research, and metabolic research.”

Learn more about Dr. Dayna’s research. Read NIDCD fact sheets on smell and taste.

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