Global diversity in the TAS2R38 bitter taste receptor: revisiting a classic evolutionary PROPosal.

Davide S Risso,Stephen Wooding,Sergio Tofanelli,Donata Luiselli,Luca Pagani,Massimo Mezzavilla,Paolo Gasparini,Gabriella Morini,Dennis Drayna,Antonietta Robino,Roberto Barale,Maura Carrai,Fabio Caradonna,Daniele Campa

doi:10.1038/srep25506

Abstract

The ability to taste phenylthiocarbamide (PTC) and 6-n-propylthiouracil (PROP) is a polymorphic trait mediated by the TAS2R38 bitter taste receptor gene. It has long been hypothesized that global genetic diversity at this locus evolved under pervasive pressures from balancing natural selection. However, recent high-resolution population genetic studies of TAS2Rs suggest that demographic events have played a critical role in the evolution of these genes. We here utilized the largest TAS2R38 database yet analyzed, consisting of 5,589 individuals from 105 populations, to examine natural selection, haplotype frequencies and linkage disequilibrium to estimate the effects of both selection and demography on contemporary patterns of variation at this locus. We found signs of an ancient balancing selection acting on this gene but no post Out-Of-Africa departures from neutrality, implying that the current observed patterns of variation can be predominantly explained by demographic, rather than selective events. In addition, we found signatures of ancient selective forces acting on different African TAS2R38 haplotypes. Collectively our results provide evidence for a relaxation of recent selective forces acting on this gene and a revised hypothesis for the origins of the present-day worldwide distribution of TAS2R38 haplotypes.

Highlights

A longstanding question has been the reason for the presence of two high-frequency haplotypes in worldwide populations
It has been suggested that pathogens may have been the real targets of natural selection, since bitter receptors are expressed in the respiratory and enteric system[16,17] and one study suggested that common polymorphisms in the TAS2R38 gene were linked to significant differences in the ability of the upper respiratory cells to clear and kill bacteria[18]
It has been suggested that a correlation may exist between PROP taster status and dietary intake[21], which could have important evolutionary consequences, a hypothesis supported by the results of a number of previous studies[22,23,24]

Summary

Introduction

A longstanding question has been the reason for the presence of two high-frequency haplotypes in worldwide populations. Because the perception of bitter taste is thought to protect us from the ingestion of toxic substances, how could the presumably non-functional AVI haplotype come to high frequency in populations worldwide? Analyses of the frequency distribution of TAS2R38 haplotypes in different populations showed significant positive values for Tajima’s D statistic, low FST values (0.001–0.05) and a deep coalescent time (TMRCA ~1 million years old) for this locus[9,14], providing evidence that balancing selection maintained both the taster and non-taster alleles at high frequency. Balancing selection hypotheses have suggested the possibility that the AVI non-taster allele encodes a fully functional receptor for another hypothetical bitter substance[8]. We studied the distribution of TAS2R38 haplotypes in a large number of human populations and available archaic hominid genomes to provide a fine-scale view of worldwide TAS2R38 diversity, and we applied selection tests to evaluate the processes underlying the evolution of TAS2R38 haplotypes

Methods

Results

Conclusion