Evolution of functionally diverse alleles associated with PTC bitter taste sensitivity in Africa.

Department of Genetics, University of Pennsylvania, PA, USA.
Molecular Biology and Evolution (Impact Factor: 14.31). 11/2011; 29(4):1141-53. DOI: 10.1093/molbev/msr293
Source: PubMed

ABSTRACT Although human bitter taste perception is hypothesized to be a dietary adaptation, little is known about genetic signatures of selection and patterns of bitter taste perception variability in ethnically diverse populations with different diets, particularly from Africa. To better understand the genetic basis and evolutionary history of bitter taste sensitivity, we sequenced a 2,975 bp region encompassing TAS2R38, a bitter taste receptor gene, in 611 Africans from 57 populations in West Central and East Africa with diverse subsistence patterns, as well as in a comparative sample of 132 non-Africans. We also examined the association between genetic variability at this locus and threshold levels of phenylthiocarbamide (PTC) bitterness in 463 Africans from the above populations to determine how variation influences bitter taste perception. Here, we report striking patterns of variation at TAS2R38, including a significant excess of novel rare nonsynonymous polymorphisms that recently arose only in Africa, high frequencies of haplotypes in Africa associated with intermediate bitter taste sensitivity, a remarkably similar frequency of common haplotypes across genetically and culturally distinct Africans, and an ancient coalescence time of common variation in global populations. Additionally, several of the rare nonsynonymous substitutions significantly modified levels of PTC bitter taste sensitivity in diverse Africans. While ancient balancing selection likely maintained common haplotype variation across global populations, we suggest that recent selection pressures may have also resulted in the unusually high level of rare nonsynonymous variants in Africa, implying a complex model of selection at the TAS2R38 locus in African populations. Furthermore, the distribution of common haplotypes in Africa is not correlated with diet, raising the possibility that common variation may be under selection due to their role in nondietary biological processes. In addition, our data indicate that novel rare mutations contribute to the phenotypic variance of PTC sensitivity, illustrating the influence of rare variation on a common trait, as well as the relatively recent evolution of functionally diverse alleles at this locus.

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    ABSTRACT: Bitter taste perception, mediated by receptors encoded by the TAS2R loci, has important roles in human health and nutrition. Prior studies have demonstrated that nonsynonymous variation at site 516 in the coding exon of TAS2R16, a bitter taste receptor gene on chromosome 7, has been subject to positive selection and is strongly correlated with differences in sensitivity to salicin, a bitter anti-inflammatory compound, in human populations. However, a recent study suggested that the derived G-allele at rs702424 in the TAS2R16 promoter has also been the target of recent selection and may have an additional effect on the levels of salicin bitter taste perception. Here, we examined alleles at rs702424 for signatures of selection using Extended Haplotype Homozygosity (EHH) and FST statistics in diverse populations from West Central, Central and East Africa. We also performed a genotype-phenotype analysis of salicin sensitivity in a subset of 135 individuals from East Africa. Based on our data, we did not find evidence for positive selection at rs702424 in African populations, suggesting that nucleotide position 516 is likely the site under selection at TAS2R16. Moreover, we did not detect a significant association between rs702424 alleles and salicin bitter taste recognition, implying that this site does not contribute to salicin phenotypic variance. Overall, this study of African diversity provides further information regarding the genetic architecture and evolutionary history of a biologically-relevant trait in humans.Journal of Human Genetics advance online publication, 1 May 2014; doi:10.1038/jhg.2014.29.
    Journal of Human Genetics 05/2014; 59(6). DOI:10.1038/jhg.2014.29 · 2.53 Impact Factor
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    ABSTRACT: Background Human bitter taste receptors are encoded by a gene family consisting of 25 functional TAS2R loci. In addition, humans carry 11 TAS2R pseudogenes, some of which display evidence for substantial diversification among species, showing lineage-specific loss of function. Since bitter taste is thought to help prevent the intake of toxic substances, diversity at TAS2R genes could reflect the action of natural selection on the ability to recognize some bitter compounds rather than others. Whether species-specific variation in TAS2R pseudogenes is solely the result of genetic drift or whether it may have been influenced by selection due to different feeding behaviors has been an open question.ResultsIn this study, we analyzed patterns of variation at human TAS2R pseudogenes in both African and non-African populations, and compared them to those observable in nonhuman primates and archaic human species. Our results showed a similar worldwide distribution of allelic variation for most of the pseudogenes, with the exception of the TAS2R6P and TAS2R18P loci, both of which presented an unexpected higher frequency of derived alleles outside Africa. At the TAS2R6P locus, two SNPs were found in strong linkage disequilibrium (r2¿>¿0.9) with variants in the functional TAS2R5 gene, which showed signatures of selection. The human TAS2R18P carried a species-specific stop-codon upstream of four polymorphic insertions in the reading frame. SNPs at this locus showed significant positive values in a number of neutrality statistics, and age estimates indicated that they arose after the homo-chimp divergence.Conclusions The similar distribution of variation of many human bitter receptor pseudogenes among human populations suggests that they arose from the ancestral forms by a unidirectional loss of function. However we explain the higher frequency of TAS2R6P derived alleles outside Africa as the effect of the balancing selection acting on the closely linked TAS2R5 gene. In contrast, TAS2R18P displayed a more complex history, suggesting an acquired function followed by a recent pseudogenization that predated the divergence of human modern and archaic species, which we hypothesize was associated with adaptions to dietary changes.
    BMC Evolutionary Biology 09/2014; 14(1):198. DOI:10.1186/s12862-014-0198-8 · 3.41 Impact Factor
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    ABSTRACT: Arguably, the most widely endorsed account of normative functions in philosophy of biology is an etiological theory that holds that the function of current traits is fixed by the past selection history of other traits of that type. The earlier formulations of this “selected-effects” theory had trouble accommodating vestigial traits. In order to remedy these difficulties, the influential recent selection or modern history selected-effects theory was introduced. This paper expands upon and strengthens the argument that this theory has trouble stemming from recent “no variation” cases. In addition, several influential arguments for the necessity of including a selection requirement in a theory of normative biological functions are contested. It is suggested that accounting for biological functions in certain areas of biology (such as physiology and the neurosciences) does not require adverting to selection.
    Biology and Philosophy 09/2014; 29(5). DOI:10.1007/s10539-014-9430-6 · 0.91 Impact Factor


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Jun 3, 2014