A bitter taste may elicit a grimace, and indeed many bitter substances are toxic and should be avoided. Yet some foods and drugs taste bitter but promote or protect health—think broccoli or quinine.

The tie between bitter taste perception and health make it an appealing research subject for scientists interested in evolution, including Penn geneticists Michael Campbell, a postdoctoral researcher in the Department of Genetics in the Perelman School of Medicine, and Sarah Tishkoff, a Penn Integrates Knowledge Professor with appointments in the Department of Genetics and the Department of Biology in the School of Arts & Sciences.

Most recently, Campbell, Tishkoff, and colleagues have studied the gene TAS2R16, which is involved in sensing the bitter-tasting compound salicin. This compound is found in aspirin, as well as some vegetables and fruits, and has anti-inflammatory properties—but it is toxic in large doses.

Writing in the journal Molecular Biology and Evolution, the researchers centered their study on Africa to begin to tease out the evolutionary history of TAS2R16.

“Because Africa is the site of origin of all modern humans, Africans are going to have a large amount of diversity, and non-Africans are going to have a subset of that diversity,” Tishkoff says.

In a three-part study, the Penn-led team studied TAS2R16 on the cellular level, on the genetic level, and on the level of sensory perception. They sequenced the gene in 595 Africans from 74 ethnically and culturally diverse populations, and compared the sequences to those of 94 non-Africans. They also had a subset of the Africans perform a taste test to determine their sensitivity to salicin.

Their investigations identified 15 TAS2R16 variants, one of which was found at high frequency in East African and non-African populations, and was associated with an increased sensitivity to bitter taste in the individuals tested. In cell-level experiments, this mutation appeared to result in increased surface expression of receptors that bind salicin molecules compared to the other variants.

“That does make you wonder if this mutation confers a selective advantage,” Tishkoff says.

The researchers’ genetic analyses showed signs that this may be the case, suggesting that this particular form of the gene was ferried through generations since arising 1.1 million years ago, and it was likely selected for at some point in our human history because it boosted the likelihood of survival and reproductive fitness in those individuals who carried it.

Yet, contrary to what might be expected, the reason for these advantages might not be related to taste, according to the researchers’ analyses. There was no discernable link between the diets of the populations studied and the prevalence of the “highly sensitive” form of the gene. Instead, the researchers hypothesize that TAS2R16 may not only alter tasting ability, but may also play a role in metabolism, lung function, or immune response.

“We’re starting to understand that these taste receptors are involved in so many functions other than just oral sensory perception,” Campbell says.