Origin and Differential Selection of Allelic Variation at TAS2R16 Associated with Salicin Bitter Taste Sensitivity in Africa

Abstract

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.

Genetic history of the African Sahelian populations

“…The largest number of haplotypes/SNPs in the single exon of TAS2R16 (876 bp long) was found in African populations, which is consistent with studies investigating other genetic loci . For TAS2R16 , however, African populations do not cluster according to shared ancestry but do structure according to geographical areas which fits expectations from the hypothesis of adaptation to local environments …”

“…It is responsible for the recognition of bitter β-D-glucopyranosides occurring in nature, such as salicin in willow bark, linamarin in manioc, and other compounds, many of which are cyanogenic, thus highly toxic. 103,104 The largest number of haplotypes/SNPs in the single exon of TAS2R16 (876 bp long) was found in African populations, 97,104,105 which is consistent with studies investigating other genetic loci. 4,106,107 For TAS2R16, however, African populations do not cluster according to shared ancestry but do structure according to geographical areas 105 which fits expectations from the hypothesis of adaptation to local environments.…”

“…In central and west central Africa, the T‐allele occurs at a lower frequency (50%‐79%), with the exception of the Fulani from Cameroon; its frequency in this population (~89%) fits the east African range, and a selection signature was also detected. In Eurasia, the derived T‐allele was found in all samples examined so far, suggesting that it is probably fixed outside of Africa …”

“…In Eurasia, the derived T-allele was found in all samples examined so far, suggesting that it is probably fixed outside of Africa. 105 Although Fulani speak today a language with clear ties to west Africa (as stated above, Fulfulde is a member of the Niger-Congo west-Atlantic subfamily), they display genetic links with both east African and west African and even with Eurasian populations. 1,69,78,91,108,109 Contrary to uniparental loci the G516T could reflect an ancestry of the Fulani in eastern or north-eastern Africa.…”

The pharmacology of bitter taste receptors and their role in human airways

“…K. Kim et al, 2003;Ledda et al, 2014), TAS2R31 (Roudnitzky et al, 2011) and TAS2R16 (Campbell et al, 2014). Bitter taste perception may be correlated (at least in part) with the level of TAS2R38 gene expression in taste cells (Lipchock et al, 2013).…”