@article{fdi:010061791,
  title = {{O}rigin and differential selection of allelic variation at {TAS}2{R}16 associated with salicin bitter taste sensitivity in {A}frica},
  author = {{C}ampbell, {M}. {C}. and {R}anciaro, {A}. and {Z}inshteyn, {D}. and {R}awlings-{G}oss, {R}. and {H}irbo, {J}. and {T}hompson, {S}. and {W}oldemeskel, {D}. and {F}roment, {A}lain and {R}ucker, {J}. {B}. and {O}mar, {S}. {A}. and {B}odo, {J}. {M}. and {N}yambo, {T}. and {B}elay, {G}. and {D}rayna, {D}. and {B}reslin, {P}. {A}. {S}. and {T}ishkoff, {S}. {A}.},
  editor = {},
  language = {{ENG}},
  abstract = {{B}itter taste perception influences human nutrition and health, and the genetic variation underlying this trait may play a role in disease susceptibility. {T}o 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 {TAS}2{R}16, a bitter taste receptor gene, in 595 individuals from 74 {A}frican populations and in 94 non-{A}fricans from 11 populations. {W}e also performed genotype-phenotype association analyses of threshold levels of sensitivity to salicin, a bitter anti-inflammatory compound, in 296 individuals from {C}entral and {E}ast {A}frica. {I}n addition, we characterized {TAS}2{R}16 mutants in vitro to investigate the effects of polymorphic loci identified at this locus on receptor function. {H}ere, we report striking signatures of positive selection, including significant {F}ay and {W}u's {H} statistics predominantly in {E}ast {A}frica, indicating strong local adaptation and greater genetic structure among {A}frican populations than expected under neutrality. {F}urthermore, 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. {I}n contrast, haplotypes carrying the "low-sensitivity" ancestral allele at site 516 showed evidence of strong purifying selection. {W}e also demonstrated, for the first time, the functional effect of nonsynonymous variation at site 516 on salicin phenotypic variance in vivo in diverse {A}fricans and showed that most other nonsynonymous substitutions have weak or no effect on cell surface expression in vitro, suggesting that one main polymorphism at {TAS}2{R}16 influences salicin recognition. {A}dditionally, we detected geographic differences in levels of bitter taste perception in {A}frica not previously reported and infer an {E}ast {A}frican origin for high salicin sensitivity in human populations.},
  keywords = {selection on standing variation ; {A}frican genetic diversity ; genotype-phenotype association ; salicin taste perception ; {AFRIQUE}},
  booktitle = {},
  journal = {{M}olecular {B}iology and {E}volution},
  volume = {31},
  numero = {2},
  pages = {288--302},
  ISSN = {0737-4038},
  year = {2014},
  DOI = {10.1093/molbev/mst211},
  URL = {https://www.documentation.ird.fr/hor/fdi:010061791},
}