Document Detail

Worldwide haplotype diversity and coding sequence variation at human bitter taste receptor loci.
MedLine Citation:
PMID:  16086309     Owner:  NLM     Status:  MEDLINE    
Bitter taste perception in humans is mediated by receptors encoded by 25 genes that together comprise the TAS2R (or T2R) gene family. The ability to identify the ligand(s) for each of these receptors is dependent on understanding allelic variation in TAS2R genes, which may have a significant effect on ligand recognition. To investigate the extent of coding variation among TAS2R alleles, we performed a comprehensive evaluation of sequence and haplotype variation in the human bitter taste receptor gene repertoire. We found that these genes exhibit substantial coding sequence diversity. In a worldwide population sample of 55 individuals, we found an average of 4.2 variant amino acid positions per gene. In aggregate, the 24 genes analyzed here, along with the phenylthiocarbamide (PTC) receptor gene analyzed previously, specify 151 different protein coding haplotypes. Analyses of the ratio of synonymous and nonsynonymous nucleotide substitutions using the Ka/Ks ratio revealed an excess of amino acid substitutions relative to most other genes examined to date (Ka/Ks = 0.94). In addition, comparisons with more than 1,500 other genes revealed that levels of diversity in the TAS2R genes were significantly greater than expected (pi = 0.11%; p < 0.01), as were levels of differentiation among continental populations (FST = 0.22; p < 0.05). These diversity patterns indicate that unusually high levels of allelic variation are found within TAS2R loci and that human populations differ appreciably with respect to TAS2R allele frequencies. Diversity in the TAS2R genes may be accounted for by natural selection, which may have favored alleles responsive to toxic, bitter compounds found in plants. These findings are consistent with the view that different alleles of the TAS2R genes encode receptors that recognize different ligands, and suggest that the haplotypes we have identified will be important in studies of receptor-ligand recognition.
Unkyung Kim; Stephen Wooding; Dante Ricci; Lynn B Jorde; Dennis Drayna
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Human mutation     Volume:  26     ISSN:  1098-1004     ISO Abbreviation:  Hum. Mutat.     Publication Date:  2005 Sep 
Date Detail:
Created Date:  2005-08-18     Completed Date:  2006-07-28     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  9215429     Medline TA:  Hum Mutat     Country:  United States    
Other Details:
Languages:  eng     Pagination:  199-204     Citation Subset:  IM    
Department of Biology, Kyungpook National University, Daegu, Republic of Korea.
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MeSH Terms
Genetic Variation*
Haplotypes / genetics*
Polymorphism, Single Nucleotide
Receptors, Cell Surface / genetics*
Receptors, G-Protein-Coupled
Selection, Genetic
Sequence Analysis, DNA
Taste Buds / physiology
Grant Support
Reg. No./Substance:
0/Ligands; 0/Receptors, Cell Surface; 0/Receptors, G-Protein-Coupled; 0/taste receptors, type 2

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