Worldwide haplotype diversity and coding sequence variation at human bitter taste receptor loci

Area of Science:

• Genetics
• Human Physiology
• Molecular Biology

Background:

• Bitter taste perception is mediated by the TAS2R gene family.
• Understanding allelic variation in TAS2R genes is crucial for identifying specific bitter taste ligands.
• Previous research has laid groundwork for exploring TAS2R gene variations.

Purpose of the Study:

• To comprehensively evaluate sequence and haplotype variation within the human TAS2R gene repertoire.
• To investigate the extent of coding variation among TAS2R alleles and its impact on ligand recognition.

Main Methods:

• Analysis of sequence and haplotype variation across 25 TAS2R genes in a worldwide population sample.
• Calculation of synonymous and nonsynonymous nucleotide substitution ratios (Ka/Ks).
• Comparison of TAS2R gene diversity and differentiation with over 1,500 other human genes.

Main Results:

• TAS2R genes exhibit substantial coding sequence diversity, with an average of 4.2 variant amino acid positions per gene.
• 151 distinct protein-coding haplotypes were identified across 24 TAS2R genes and the PTC receptor gene.
• TAS2R genes showed significantly higher levels of diversity (pi = 0.11%) and continental population differentiation (FST = 0.22) compared to most other genes.

Conclusions:

• TAS2R loci harbor unusually high levels of allelic variation, with significant differences in allele frequencies among human populations.
• Natural selection, potentially favoring alleles responsive to toxic plant compounds, likely accounts for this diversity.
• Identified TAS2R haplotypes are important for future studies on bitter taste receptor-ligand recognition.