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AUGUST 2005

Toxins Drove Evolution Of Human Taste Sense

Edited By Herman Rosen, MD

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 poisons. Today, however, the same sensory sensitivity may have adverse consequences for human health, 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. 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 researchers included David Goldstein, Ph.D., of the Duke Institute for Genome Sciences & Policy and Nicole Soranzo, Ph.D., of the University College London. 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 that responds to toxic compounds which 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 and are present in various foods, including cassava, almonds, green tea and some beans. They found that taste receptors carrying a particular 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.” However the team reported, human populations in Africa have retained high frequencies of a lower-sensitivity bitter taste receptor variant, with a geographic distribution similar to 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.#

Dr. Herman Rosen is Clinical Professor of Medicine at Weill Medical College of Cornell University.

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