Unkyung Kim and Stephen Wooding contributed equally to this work.
Worldwide haplotype diversity and coding sequence variation at human bitter taste receptor loci†
Article first published online: 5 AUG 2005
© 2005 Wiley-Liss, Inc.
Volume 26, Issue 3, pages 199–204, September 2005
How to Cite
Kim, U., Wooding, S., Ricci, D., Jorde, L. B. and Drayna, D. (2005), Worldwide haplotype diversity and coding sequence variation at human bitter taste receptor loci. Hum. Mutat., 26: 199–204. doi: 10.1002/humu.20203
Communicated by Pui-Yan Kwok
- Issue published online: 5 AUG 2005
- Article first published online: 5 AUG 2005
- Manuscript Accepted: 17 FEB 2005
- Manuscript Received: 12 NOV 2004
- NIH. Grant Numbers: DC Z01-000046-04, HL070048, ES12125
- NSF. Grant Number: BCS0218370
- bitter taste;
- natural selection
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 (π=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. Hum Mutat 26(3), 199–204, 2005. © 2005 Wiley-Liss, Inc.