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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
agricultural and biological sciences
Origin and differential selection of allelic variation at TAS2R16 associated with salicin bitter taste sensitivity in Africa
Molecular Biology and Evolution, Volume 31, No. 2, Year 2014
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Description
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. © 2013 The Author.
Available Materials
https://efashare.b-cdn.net/share/pmc/articles/PMC3907056/bin/supp_31_2_288__index.html
https://efashare.b-cdn.net/share/pmc/articles/PMC3907056/bin/supp_mst211_Final_Supplemental_Figures_MBE-13-0486.pdf
https://efashare.b-cdn.net/share/pmc/articles/PMC3907056/bin/supp_mst211_Final_Supplemental_Tables_for_MBE-13-0486.xls
Authors & Co-Authors
Campbell, Michael C.
United States, Philadelphia
University of Pennsylvania
Ranciaro, Alessia
United States, Philadelphia
University of Pennsylvania
Zinshteyn, Daniel
United States, Philadelphia
University of Pennsylvania
Rawlings-Goss, Renata
United States, Philadelphia
University of Pennsylvania
Hirbo, Jibril B.
United States, Philadelphia
University of Pennsylvania
Thompson, Simon R.
United States, Philadelphia
University of Pennsylvania
Woldemeskel, Dawit
United States, Philadelphia
University of Pennsylvania
Ethiopia, Addis Ababa
Addis Ababa University
Froment, Alain
France, Paris
Museé de L'homme
Rucker, Joseph B.
United States, Philadelphia
Integral Molecular, Inc.
Omar, Sabah Ahmed
Kenya, Nairobi
Kenya Medical Research Institute
Bodo, Jean Marie
Cameroon, Yaounde
Ministry of Scientific Research and Innovation-cameroon
Nyambo, Thomas B.
Tanzania, Dar es Salaam
Muhimbili University of Health and Allied Sciences
Belay, Gurja
Ethiopia, Addis Ababa
Addis Ababa University
Drayna, Dennis
United States, Bethesda
National Institute on Deafness and Other Communication Disorders Nidcd
Breslin, Paul A.S.
United States, Philadelphia
Monell Chemical Senses Center
United States, New Brunswick
Rutgers University–new Brunswick
Tishkoff, Sarah A.
United States, Philadelphia
University of Pennsylvania
Statistics
Citations: 43
Authors: 16
Affiliations: 10
Identifiers
Doi:
10.1093/molbev/mst211
ISSN:
07374038
e-ISSN:
15371719
Research Areas
Food Security
Genetics And Genomics
Study Locations
Multi-countries