Evolution of Functionally Diverse Alleles Associated with PTC Bitter Taste Sensitivity in Africa
Evolution of Functionally Diverse Alleles Associated with PTC Bitter Taste Sensitivity in Africa
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DOI：
10.1093/molbev/msr293
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发表时间：
2012-04-01
影响因子：
10.7
通讯作者：
Tishkoff, Sarah A.
中科院分区：
文献类型：
--
作者：
Campbell, Michael C.;Ranciaro, Alessia;Tishkoff, Sarah A.
虽然人类的苦味感知被假设为是一种饮食适应，但人们对具有不同饮食的种族多样性人群（特别是来自非洲的人群）的苦味感知变异性的选择和模式的遗传特征知之甚少。为了更好地了解苦味敏感性的遗传基础和进化历史，我们对来自中西部和东非57个不同生存模式人群的611名非洲人以及132名非非洲人的比较样本中包含苦味受体基因TAS2R38的2，975 bp区域进行了测序。我们还研究了463名来自上述人群的非洲人在该位点的遗传变异性与苯硫脲（PTC）苦味阈值水平之间的关联，以确定变异如何影响苦味感知。在这里，我们报告了TAS2R38的惊人的变异模式，包括最近仅在非洲出现的新的罕见的非同义多态性，非洲与中等苦味敏感性相关的单倍型的高频率，在遗传和文化上不同的非洲人中常见单倍型的频率非常相似，以及全球人群中常见变异的古老合并时间。此外，几种罕见的非同义取代显着改变了不同非洲人的PTC苦味敏感性水平。虽然古老的平衡选择可能保持了全球人群中常见的单倍型变异，但我们认为，最近的选择压力也可能导致非洲罕见的非同义变异异常高，这意味着非洲人群中TAS2R38位点的选择模型复杂。此外，非洲常见单倍型的分布与饮食无关，这增加了常见变异可能由于其在非饮食生物学过程中的作用而受到选择的可能性。此外，我们的数据表明，新的罕见突变有助于PTC敏感性的表型变异，说明罕见变异对共同性状的影响，以及该基因座功能多样的等位基因的相对较新的进化。
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.