title: Global diversity in the TAS2R38 bitter taste receptor: revisiting a classic evolutionary PROPosal.
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.
authors.affiliation: National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.|Department of Biological, Geological and Environmental Sciences BiGeA, Laboratory of Molecular Anthropology and Centre for Genome Biology, University of Bologna, via Selmi 3, 40126 Bologna, Italy.
authors.forename: Davide S
authors.initials: DS
authors.lastname: Risso
authors.affiliation: Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", University of Trieste, 34137 Trieste, Italy.|Division of Experimental Genetics, Sidra Medical and Research Center, Doha, Qatar.
authors.forename: Massimo
authors.initials: M
authors.lastname: Mezzavilla
authors.affiliation: Department of Biological, Geological and Environmental Sciences BiGeA, Laboratory of Molecular Anthropology and Centre for Genome Biology, University of Bologna, via Selmi 3, 40126 Bologna, Italy.|Division of Biological Anthropology, University of Cambridge, CB2 1QH, Cambridge, UK.
authors.forename: Luca
authors.initials: L
authors.lastname: Pagani
authors.affiliation: Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", University of Trieste, 34137 Trieste, Italy.
authors.forename: Antonietta
authors.initials: A
authors.lastname: Robino
authors.affiliation: University of Gastronomic Sciences, Piazza Vittorio Emanuele 9, Bra, Pollenzo 12042, CN, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Morini
authors.affiliation: Department of Biology, University of Pisa, Via Ghini 13, 56126 Pisa, Italy.
authors.forename: Sergio
authors.initials: S
authors.lastname: Tofanelli
authors.affiliation: Department of Biology, University of Pisa, Via Ghini 13, 56126 Pisa, Italy.
authors.forename: Maura
authors.initials: M
authors.lastname: Carrai
authors.affiliation: Department of Biology, University of Pisa, Via Ghini 13, 56126 Pisa, Italy.
authors.forename: Daniele
authors.initials: D
authors.lastname: Campa
authors.affiliation: Department of Biology, University of Pisa, Via Ghini 13, 56126 Pisa, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Barale
authors.affiliation: Biological, Chemical and Pharmaceutical Sciences and Technologies Department, STEBICEF, Università degli Studi di Palermo, V.le delle Scienze, Edificio 16, 90128 Palermo, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Caradonna
authors.affiliation: Institute for Maternal and Child Health, IRCCS "Burlo Garofolo", University of Trieste, 34137 Trieste, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Gasparini
authors.affiliation: Department of Biological, Geological and Environmental Sciences BiGeA, Laboratory of Molecular Anthropology and Centre for Genome Biology, University of Bologna, via Selmi 3, 40126 Bologna, Italy.
authors.forename: Donata
authors.initials: D
authors.lastname: Luiselli
authors.affiliation: Health Sciences Research Institute, University of California at Merced, 5200 North Lake Road, Merced, CA 95343, USA.
authors.forename: Stephen
authors.initials: S
authors.lastname: Wooding
authors.affiliation: National Institute on Deafness and Other Communication Disorders, NIH, Bethesda, MD 20892, USA.
authors.forename: Dennis
authors.initials: D
authors.lastname: Drayna
mesh_terms: D030541:Databases, Genetic; D019143:Evolution, Molecular; D014644:Genetic Variation; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D010670:Phenylthiourea / Q000737:chemistry; D011441:Propylthiouracil / Q000737:chemistry; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012641:Selection, Genetic / Q000235:genetics*; D013649:Taste / Q000235:genetics*; D000098706:Taste Receptors, Type 2
chemical_list: D043562:Receptors, G-Protein-Coupled; D000098706:Taste Receptors, Type 2; D010670:Phenylthiourea; D011441:Propylthiouracil