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. 2022 Oct 11:13:952299.
doi: 10.3389/fgene.2022.952299. eCollection 2022.

Global population genetics and diversity in the TAS2R bitter taste receptor family

Stephen P Wooding  1 , Vicente A Ramirez  2
Affiliations

Global population genetics and diversity in the TAS2R bitter taste receptor family

Stephen P Wooding et al. Front Genet. .

Abstract

Bitter taste receptors (TAS2Rs) are noted for their role in perception, and mounting evidence suggests that they mediate responses to compounds entering airways, gut, and other tissues. The importance of these roles suggests that TAS2Rs have been under pressure from natural selection. To determine the extent of variation in TAS2Rs on a global scale and its implications for human evolution and behavior, we analyzed patterns of diversity in the complete 25 gene repertoire of human TAS2Rs in ∼2,500 subjects representing worldwide populations. Across the TAS2R family as a whole, we observed 721 single nucleotide polymorphisms (SNPs) including 494 nonsynonymous SNPs along with 40 indels and gained and lost start and stop codons. In addition, computational predictions identified 169 variants particularly likely to affect receptor function, making them candidate sources of phenotypic variation. Diversity levels ranged widely among loci, with the number of segregating sites ranging from 17 to 41 with a mean of 32 among genes and per nucleotide heterozygosity (π) ranging from 0.02% to 0.36% with a mean of 0.12%. F ST ranged from 0.01 to 0.26 with a mean of 0.13, pointing to modest differentiation among populations. Comparisons of observed π and F ST values with their genome wide distributions revealed that most fell between the 5th and 95th percentiles and were thus consistent with expectations. Further, tests for natural selection using Tajima's D statistic revealed only two loci departing from expectations given D's genome wide distribution. These patterns are consistent with an overall relaxation of selective pressure on TAS2Rs in the course of recent human evolution.

Keywords: evolution; genetics; perception; selection; taste.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
Variation across TAS2R substructures. (A) Coordinates, lengths, and numbers of variable and PHI sites in external loops (ELs), transmembrane (TMs), and internal loops (ILs). N-terminus and C-terminus sites were categorized as EL and IL, respectively. (B) Distribution of variability across amino acid positions. Shading indicates the number of TAS2Rs variable at the indicated position, which ranged from 0 to 9 of 23 receptors. Positions affected by PHI variants are indicated in bold.
FIGURE 2
FIGURE 2
Distributions of π, Tajima’s D, and F ST in the 1000GP. Values observed in TAS2Rs and genome-wide sliding windows are shown in the left and right of each panel, respectively. (A) π distributions. Mean values in TAS2Rs and genome-wide were 0.0012 and 0.0009, respectively. (B) D distributions. Mean values in TAS2Rs and genome-wide were −1.61 and −1.59 and. (C) F ST distributions. Mean values in TAS2Rs and genome-wide were 0.13 and 0.08.
FIGURE 3
FIGURE 3
Principal components plots. (A) All sites. (B) Synonymous sites only. (C) Nonsynonymous sites only.
See this image and copyright information in PMC

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