Phenylthiocarbamide: a 75-year adventure in genetics and natural selection.

VARIATION in taste sensitivity to the bitter compound phenylthiocarbamide (PTC) is one of the best known Mendelian traits in human populations, ranking alongside eye color and blood types in the canon of classic examples. Much of PTC’s appeal arises from the fact that it is nearly impossible to guess one’s phenotype until explicitly tested, yet, when tested, the phenotype is so striking as to be amusing. This property is important, particularly in education, because it can spice up lessons on inheritance. Less obvious, especially today, is PTC’s appeal as an easily typed yet highly informative genetic marker. It was this aspect of the trait that made PTC an important instrument in the earliest efforts to dissect the human genome. Variation in PTC sensitivity has also had long-standing appeal from an evolutionary standpoint. The connection of variable taste sensitivity with an aspect of behavior so obviously connected to fitness—diet choice— has long raised a basic question: Has natural selection been acting on this trait? It was this question that motivated the great statistician, R. A. Fisher, and his friends E. B. Ford and Julian Huxley, to perform what appears to be the first test for natural selection in a specific human gene. In an often-overlooked article published in 1939 (listed by Science Citation Index as having been cited ,50 times in the ensuing 65 years), Fisher et al. (1939) reported that chimpanzees, like humans, show variable sensitivity to PTC. This, they argued, is strong evidence that balancing natural selection must have actively maintained variation at the locus from a time prior to the human–chimp divergence. While littleknown today, this article set the stage for what has become an industry in the field of genetics. THE DISCOVERY OF VARIABLE PTC SENSITIVITY