predominated in areas of Africa with endemic malaria, where only 15.6% carried the N172 allele. Such a high frequency of derived allele is "a signature of positive selection," Soranzo told The Scientist, and statistical tests like the Fay and Wu test on these data confirmed this hypothesis.
To test the alleles' phenotypic effects, the authors used in vitro calcium imaging and found that those cells expressing the N172 allele were more sensitive to bitter compounds. These results suggest that the allele became more prevalent in non-African populations to protect them from toxins in plants they might have encountered outside the continent, Dennis Drayna, of the National Institutes of Health, who did not participate in the study, told The Scientist via E-mail.
"As these populations move out, if they start encountering the cyanogenic glycoside [containing] plants, then the ones that have the receptor with the higher binding affinity may be more likely to taste the cyanogenic glycosides and stop feeding before they kill themselves," Glendinning said.
The fact that the K ancestral form is still prevalent in African populations, and particularly in Central Africa, could be explained by a selective advantage against malaria, the authors suggest. Previous work has linked chronic low-level ingestion of cyanide with lowered malaria risk, with the idea that increased levels of cyanide in the bloodstream could make humans less hospitable hosts for the parasite, Glendinning said. In the current study, living in lower-malaria-risk countries was correlated with a higher frequency of the less taste-sensitive allele.
"One could speculate that the reduced sensitivity towards this compound could help to increase intake of cyanide in the diet, and this in turn could have an evolutionary advantage by protecting against malaria infection," Soranzo said. The connection is "completely speculative at this point" but "worth exploring," she said.
These findings present a different evolutionary story-one of "local adaptation," according to Wooding-than the other well-characterized bitter taste receptor: TAS2R38, for PTC. The allele distribution for TAS2R38 demonstrates balancing selection, maintaining two distinct alleles in populations, which may allow a greater range of bitter taste recognition, according to a paper Wooding and Drayna published last year.
According to Glendinning and Drayna, experiments must now be conducted on humans to confirm the functional effect of the variants. "It's a big jump from a...cell expressing a particular G protein-coupled receptor [to] the human brain," Glendinning said. Coauthor Bernd Bufe, of the German Institute of Human Nutrition, said the team will use "taste tests to determine threshold levels" as he did in a previous paper.
"One of the very nice things about this study is that it suggests a very concrete hypothesis that might be tested in populations where malaria is present," Wooding told The Scientist. "It would be very interesting to return to those populations and find out whether people who are more or less sensitive to these compounds really do eat more of these plant compounds that protect them from malaria."
N. Soranzo et al., "Positive selection on a high-sensitivity allele of the human bitter-taste receptor TAS2R16," Current Biology, 15:1257-65, July 26, 2005.
John I. Glendinning
F. Jackson et al., "Two evolutionary models for the interactions of dietary cyanogens, hemoglobin S, and falciparum malaria." Am J. Human Biology, 2(5):521-532, May 1990.