Origin and Differential Selection of Allelic Variation at TAS2R16 Associated with Salicin Bitter Taste Sensitivity in Africa
Bitter taste perception influences human nutrition and health, and the
genetic variation underlying this trait may play a
role in disease susceptibility. To better
understand the genetic architecture and patterns of phenotypic
variability of bitter
taste perception, we sequenced a 996 bp region,
encompassing the coding exon of TAS2R16, a bitter taste
receptor gene, in 595 individuals from 74 African populations, and in 94
non-Africans from 11 populations.
We also performed genotype-phenotype association
analyses of threshold levels of sensitivity to salicin, a bitter
anti-inflammatory
compound, in 296 individuals from Central and East
Africa. In addition, we characterized TAS2R16 mutants in vitro
to investigate the effects of polymorphic loci identified at this locus
on receptor function. Here, we report striking signatures
of positive selection, including significant Fay
and Wu's H statistics predominantly in East Africa, indicating strong
local
adaptation, and greater genetic structure among
African populations than expected under neutrality. Furthermore, we
observed
a “star-like” phylogeny for haplotypes with the
derived allele at polymorphic site 516 associated with increased bitter
taste
perception that is consistent with a model of
selection for “high-sensitivity” variation. In contrast, haplotypes
carrying
the “low-sensitivity” ancestral allele at site 516
showed evidence of strong purifying selection. We also demonstrated, for
the first time, the functional effect of
nonsynonymous variation at site 516 on salicin phenotypic variance in vivo in diverse Africans, and showed that most other nonsynonymous substitutions have weak or no effect on cell surface expression
in vitro, suggesting that one main polymorphism at TAS2R16
influences salicin recognition. Additionally, we detected geographic
differences in levels of bitter taste perception in
Africa not previously reported, and infer an East
African origin for high salicin sensitivity in human populations.
Closed Access
From the Press:
“Because Africa is the site of origin of all modern humans,” said study author Sarah Tishkoff,
a professor in the University of Pennsylvania’s Department of Genetics,
“Africans are going to have a large amount of diversity and
non-Africans are going to have a subset of that diversity. In Africa,
you get an opportunity to observe how these genetic variants are
influencing phenotypes that you wouldn’t have if you were only studying
non-Africans.”
“The taste testing shows that the mutations in TAS2R16 had functional
significance for the bitter taste perception system,” said study author Paul Breslin, an experimental psychologist from Rutgers University. “In this case, the mutation caused a gain of taste function.”
“The types of populations we’re studying are diverse and they have
diverse diets,” Tishkoff said, “suggesting that there is likely
something else going on here. By getting a handle on how much variation
is in these populations, where it is located and what are the particular
signatures of selection, it might start giving us clues as to what we
should be looking at in terms of the biomedical or physiological
significance of these genes.”
http://www.redorbit.com/news/science/1113000905/genetic-mutation-bitter-taste-human-evolution-111213/
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It's interesting, thanks, although I am always overly cautious about "selective" explanations (almost invariably other more random explanations are equally possible and researchers seldom bother to properly justify the supposed extra fitness of the trait). In general I would expect greater diversity in Eastern (or Eastern-Central) Africa without need to appeal to selection, just because it seems to be the cradle of African Humankind (as well as of the extra-African one), but also because, in addition to that, it also seems the area with greater backflow from nearly all directions.
ReplyDeleteI don't terribly like Breslin's characterization of the mutation as a "gain in taste function." Really, to the extent that you have selection for bitter taste sensitivity you are balancing an ability to avoid poisons before having a fatal dose v. the ability to be omnivorous and avoid starvation or malnutrition (stereotypically not eating bitter vegetables like brocolli that are healthy).
ReplyDeleteIt would be interesting to know what bitter natural poison(s) in East Africa could have had that selective impact. One time frame where that kind of thing might have a selective effect distinct from any that should be shared by all modern humans as Maju suggests could be in the proto-farming stage where there is organized gathering of a non-domesticated plant that has a mimic that is poisonous - particularly in arid highland areas of East Africa.