Plant toxins in the diets of early humans drove the evolution of taste

Plant toxins in the diets of early humans drove the evolution of a bitter taste receptor better able to detect them, suggests new genetic research by scientists at University College London, Duke University Medical Center, and the German Institute of Human Nutrition.

The ability to discern bitter flavors likely offered a survival advantage by protecting ancient people from poisonous fare, the researchers concluded. Today, however, the same sensory sensitivity may have adverse consequences for human health, they added, by causing an aversion to bitter-tasting nutrients, some of which might lower the risk of cancer and heart disease.

In their study, the researchers examined the sequence of one gene encoding the bitter taste receptor TAS2R16 in 60 human populations from all over the world. By reconstructing the history of the gene, the researchers found evidence of evolutionary selection. Specifically, they found that particular derived variants of the taste receptor rapidly rose to high frequency many thousands of years ago, before the expansion of early humans out of Africa. Through further analyses they showed that one of the selected gene variants confers an increased sensitivity to particular toxins, including five that release cyanide when digested. The receptor variant also is more sensitive to certain beneficial compounds, they showed.

The team reported its findings in the July 26, 2005, issue of Current Biology. The researchers included senior author David Goldstein, Ph.D., of the Duke Institute for Genome Sciences & Policy (IGSP) and lead author Nicole Soranzo, Ph.D., of the University College London. Formerly of the University College London, Goldstein is director of the Duke Center for Population Genomics & Pharmacogenetics, one of seven IGSP centers.

Human taste senses are generally less sensitive than those of primates or other mammals, Goldstein noted. However, the new evidence for positive selection on the gene for the bitter taste receptor suggests that the preservation of specific sensory abilities may have been particularly important, at least in the earlier stages of human evolution.

"Humans have devised a number of behavioral habits to inactivate toxins in foods, such as soaking of seeds, baking or cooking," Soranzo said. "Because of these other means of protection, it is generally thought that the ability to recognize compounds through the sense of taste is less important for people than it is for other animals.

"However, detecting signatures of selection for a bitter taste receptor suggests that sensory detection of dangerous foods played an important role at certain times during the course of our evolution," she added.

In mammals, including humans, taste receptors on the tongue can detect five primary flavors: bitter, sweet, sour, salty and umami -- a savory or meaty taste. Taste receptors are protein switches that trigger signals to the brain's taste-processing centers in response to particular foods or other chemicals.

In humans, 25 genes are responsible for encoding receptors that detect bitter flavors. The current study provides the second report in humans that different variants of those taste genes contribute to variation among people in their response to bitter foods.

The researchers sequenced the bitter taste receptor gene TAS2R16 from 997 individuals representing 60 human populations. The team then retraced the gene's history by comparing human gene variants to one another and to those of primates, including chimpanzees.

TAS2R16 responds to toxic compounds that release cyanide when digested. Such toxins, called glucopyranosides, comprise a wide class of natural defense compounds synthesized by over 2,500 plant and insect species. Glucopyranosides are present in various foods items, including cassava, almonds, green tea and some beans.

The researchers identified six common variants of the TAS2R16 bitter receptor, two of which alter the receptor's amino acid content and potentially its function, they reported. Genetic and other data pointed to one variant, dubbed K172N, as the target of positive selection in human evolution. The team estimated that K172N arose during the Middle Pleistocene, 78,700 to 791,000 years ago, before the expansion of early humans out of Africa.

Further study of the receptor variant found that K172N had a clear effect on receptor function. In particular, taste receptors carrying the K172N variant exhibited increased sensitivity for five different potentially harmful, cyanide-releasing compounds. The receptor variant also showed greater sensitivity to two other compounds, salicin and arbutin, with known beneficial effects.

"Bitter compounds are a heterogeneous class, some of which are toxic and some of which lower the risk of cancer and heart disease," Soranzo said. "Owing to their bitter taste, these compounds are routinely removed by the food industry and represent a key limitation in increasing the nutrient content of plant foods.

"While this gene variant may have been advantageous in our past through avoidance of natural toxins, one might speculate that it may now contribute to increasing disease risk through lowered intake of such beneficial compounds."

Also noteworthy, the team reported, human populations in Africa have retained moderately high frequencies of a lower-sensitivity K172 bitter taste receptor variant, with a geographic distribution similar to known malaria resistance genes. Earlier work has linked chronic ingestion of low levels of cyanide-releasing foods to protection against the disease, suggesting that more limited sensitivity to bitter flavors may have been advantageous in regions where malaria was most prevalent.