Genetic variation in taste receptor pseudogenes provides evidence for a dynamic role in human evolution.
ABSTRACT: Human bitter taste receptors are encoded by a gene family consisting of 25 functional TAS2R loci. In addition, humans carry 11 TAS2R pseudogenes, some of which display evidence for substantial diversification among species, showing lineage-specific loss of function. Since bitter taste is thought to help prevent the intake of toxic substances, diversity at TAS2R genes could reflect the action of natural selection on the ability to recognize some bitter compounds rather than others. Whether species-specific variation in TAS2R pseudogenes is solely the result of genetic drift or whether it may have been influenced by selection due to different feeding behaviors has been an open question.In this study, we analyzed patterns of variation at human TAS2R pseudogenes in both African and non-African populations, and compared them to those observable in nonhuman primates and archaic human species. Our results showed a similar worldwide distribution of allelic variation for most of the pseudogenes, with the exception of the TAS2R6P and TAS2R18P loci, both of which presented an unexpected higher frequency of derived alleles outside Africa. At the TAS2R6P locus, two SNPs were found in strong linkage disequilibrium (r2?>?0.9) with variants in the functional TAS2R5 gene, which showed signatures of selection. The human TAS2R18P carried a species-specific stop-codon upstream of four polymorphic insertions in the reading frame. SNPs at this locus showed significant positive values in a number of neutrality statistics, and age estimates indicated that they arose after the homo-chimp divergence.The similar distribution of variation of many human bitter receptor pseudogenes among human populations suggests that they arose from the ancestral forms by a unidirectional loss of function. However we explain the higher frequency of TAS2R6P derived alleles outside Africa as the effect of the balancing selection acting on the closely linked TAS2R5 gene. In contrast, TAS2R18P displayed a more complex history, suggesting an acquired function followed by a recent pseudogenization that predated the divergence of human modern and archaic species, which we hypothesize was associated with adaptions to dietary changes.
Project description:The ability to detect bitter tastes is important for animals; it can help them to avoid ingesting harmful substances. Bitter taste perception is mainly mediated by bitter taste receptor proteins, which are encoded by members of the Tas2r gene family and vary with the dietary preference of a specific species. Although individuals with different genotypes differ in bitterness recognition capability, little is known about the relationship between genetic variation and food selection tendencies at the intraspecific level. In this study, we examined the relationship between genotypes and diet in plateau zokor (Eospalax baileyi), a subterranean rodent endemic to the Qinghai-Tibet Plateau that caches food for the winter. We assayed the composition and taste profile of each plant contained in temporary caches and vicinity quadrats, which were representative of selected and available food, respectively. Bitter plant selection indices (E bitter) were estimated. We also sequenced 26 candidate Tas2r genes from zokors and determined their relationships with the E bitter of their caches. We identified four key results: (1) zokors varied considerably in both bitter food preference and Tas2r sequences; (2) five genes (zTas2r115,zTas2r119,zTas2r126,zTas2r134, and zTas2r136) exhibited allelic variation that was significantly associated with E bitter; (3) synonymous SNPs, nonsynonymous SNPs, and pseudogenization are involved in the genotype-phenotype relationship; (4) the minor genotypes of zTas2r115,zTas2r134, and zTas2r136 and the major genotypes of zTas2r119 and zTas2r126 cached more bitter plants. Our results link Tas2r variation with food selection behavior at the population level for the first time.
Project description:Taste perception is crucial in monitoring food intake and, hence, is thought to play a significant role in human evolution. To gain insights into possible adaptive signatures in genes encoding bitter, sweet, and umami taste receptors, we surveyed the available sequence variation data from the 1000 Genomes Project Phase 3 for TAS1R (TAS1R1-3) and TAS2R (TAS2R16 and TAS2R38) families. Our study demonstrated that genes from these two families have experienced contrasting evolutionary histories: While TAS1R1 and TAS1R3 showed worldwide evidence of positive selection, probably correlated with improved umami and sweet perception, the patterns of variation displayed by TAS2R16 and TAS2R38 were more consistent with scenarios of balancing selection that possibly conferred a heterozygous advantage associated with better capacity to perceive a wide range of bitter compounds. In TAS2R16, such adaptive events appear to have occurred restrictively in mainland Africa, whereas the strongest evidence in TAS2R38 was detected in Europe. Despite plausible associations between taste perception and the TAS1R and TAS2R selective signatures, we cannot discount other biological mechanisms as driving the evolutionary trajectories of those TAS1R and TAS2R members, especially given recent findings of taste receptors behaving as the products of pleiotropic genes involved in many functions outside the gustatory system.
Project description:As nontraditional model organisms with extreme physiological and morphological phenotypes, snakes are believed to possess an inferior taste system. However, the bitter taste sensation is essential to distinguish the nutritious and poisonous food resources and the genomic evidence of bitter taste in snakes is largely scarce. To explore the genetic basis of the bitter taste of snakes and characterize the evolution of bitter taste receptor genes (<i>Tas2r</i>s) in reptiles, we identified <i>Tas2r</i> genes in 19 genomes (species) corresponding to three orders of non-avian reptiles. Our results indicated contractions of <i>Tas2r</i> gene repertoires in snakes, however dramatic gene expansions have occurred in lizards. Phylogenetic analysis of the <i>Tas2r</i>s with NJ and BI methods revealed that <i>Tas2r</i> genes of snake species formed two clades, whereas in lizards the <i>Tas2r</i> genes clustered into two monophyletic clades and four large clades. Evolutionary changes (birth and death) of intact <i>Tas2r</i> genes in reptiles were determined by reconciliation analysis. Additionally, the taste signaling pathway calcium homeostasis modulator 1 (<i>Calhm1</i>) gene of snakes was putatively functional, suggesting that snakes still possess bitter taste sensation. Furthermore, Phylogenetically Independent Contrasts (PIC) analyses reviewed a significant correlation between the number of <i>Tas2r</i> genes and the amount of potential toxins in reptilian diets, suggesting that insectivores such as some lizards may require more <i>Tas2r</i>s genes than omnivorous and carnivorous reptiles.
Project description:The ability to taste bitterness evolved to safeguard most animals, including humans, against potentially toxic substances, thereby leading to food rejection. Nonetheless, bitter perception is subject to individual variations due to the presence of genetic functional polymorphisms in bitter taste receptor (TAS2R) genes, such as the long-known association between genetic polymorphisms in TAS2R38 and bitter taste perception of phenylthiocarbamide. Yet, due to overlaps in specificities across receptors, such associations with a single TAS2R locus are uncommon. Therefore, to investigate more complex associations, we examined taste responses to six structurally diverse compounds (absinthin, amarogentin, cascarillin, grosheimin, quassin, and quinine) in a sample of the Caucasian population. By sequencing all bitter receptor loci, inferring long-range haplotypes, mapping their effects on phenotype variation, and characterizing functionally causal allelic variants, we deciphered at the molecular level how a subjects' genotype for the whole-family of TAS2R genes shapes variation in bitter taste perception. Within each haplotype block implicated in phenotypic variation, we provided evidence for at least one locus harboring functional polymorphic alleles, e.g. one locus for sensitivity to amarogentin, one of the most bitter natural compounds known, and two loci for sensitivity to grosheimin, one of the bitter compounds of artichoke. Our analyses revealed also, besides simple associations, complex associations of bitterness sensitivity across TAS2R loci. Indeed, even if several putative loci harbored both high- and low-sensitivity alleles, phenotypic variation depended on linkage between these alleles. When sensitive alleles for bitter compounds were maintained in the same linkage phase, genetically driven perceptual differences were obvious, e.g. for grosheimin. On the contrary, when sensitive alleles were in opposite phase, only weak genotype-phenotype associations were seen, e.g. for absinthin, the bitter principle of the beverage absinth. These findings illustrate the extent to which genetic influences on taste are complex, yet arise from both receptor activation patterns and linkage structure among receptor genes.
Project description:Variation in responsiveness to bitter-tasting compounds has been associated with differences in alcohol consumption. One strong genetic determinant of variation in bitter taste sensitivity is alleles of the TAS2R gene family, which encode chemosensory receptors sensitive to a diverse array of natural and synthetic compounds. Members of the TAS2R family, when expressed in the gustatory system, function as bitter taste receptors. To better understand the relationship between TAS2R function and alcohol consumption, we asked if TAS2R variants are associated with measures of alcohol consumption in a head and neck cancer patient cohort. Factors associated with increased alcohol intake are of strong interest to those concerned with decreasing the incidence of cancers of oral and pharyngeal structures. We found a single nucleotide polymorphism (SNP) located within the TAS2R13 gene (rs1015443 [C1040T, Ser259Asn]), which showed a significant association with measures of alcohol consumption assessed via the Alcohol Use Disorders Identification Test (AUDIT). Analyses with other SNPs in close proximity to rs1015443 suggest that this locus is principally responsible for the association. Thus, our results provide additional support to the emerging hypothesis that genetic variation in bitter taste receptors can impact upon alcohol consumption.
Project description:The 25 human bitter receptors and their respective genes (TAS2Rs) contain unusually high levels of allelic variation, which may influence response to bitter compounds in the food supply. Phenotypes based on the perceived bitterness of single bitter compounds were first linked to food preference over 50 years ago. The most studied phenotype is propylthiouracil bitterness, which is mediated primarily by the TAS2R38 gene and possibly others. In a laboratory-based study, we tested for associations between TAS2R variants and sensations, liking, or intake of bitter beverages among healthy adults who were primarily of European ancestry. A haploblock across TAS2R3, TAS2R4, and TAS2R5 explained some variability in the bitterness of espresso coffee. For grapefruit juice, variation at a TAS2R19 single nucleotide polymorphism (SNP) was associated with increased bitterness and decreased liking. An association between a TAS2R16 SNP and alcohol intake was identified, and the putative TAS2R38-alcohol relationship was confirmed, although these polymorphisms did not explain sensory or hedonic responses to sampled scotch whisky. In summary, TAS2R polymorphisms appear to influence the sensations, liking, or intake of common and nutritionally significant beverages. Studying perceptual and behavioral differences in vivo using real foods and beverages may potentially identify polymorphisms related to dietary behavior even in the absence of known ligands.
Project description:BACKGROUND: The oral GPCR nutrient/taste receptor gene repertoire consists of the Tas1r family (sweet and umami tastes), the Tas2r family (bitter taste) as well as several other potential candidate sensors of amino acids, peptones and fatty acids. Taste/nutrient receptors play a fundamental role in survival through the identification of dietary nutrients or potentially toxic compounds. In humans and rodents some variations in taste sensitivity have been related to receptor polymorphisms. Some allelic variants, in turn, have been linked to the adaptation to specific geographical locations and dietary regimes. In contrast, the porcine taste/nutrient receptor repertoire has been only partially characterized and limited information on genetic variation across breeds and geographical location exists. The present study aims at filling this void which in turn will form the bases for future improvements in pig nutrition. RESULTS: Our results show that the pig oral repertoire of taste/nutrient receptors consists of at least 28 receptor genes with significant transcription measured for 27. When compared to humans and rodents, the porcine gene sequences encoding sensors for carbohydrates, amino acids and fatty acids were highly conserved whilst the bitter taste gene family (known as Tas2rs) showed high divergence. We identified 15 porcine Tas2rs of which 13 are orthologous to human sequences. The single nucleotide polymorphism (SNP) sequence analysis using 79 pig genomes, representing 14 different breeds/populations, revealed that the Tas2r subset had higher variability (average ? =2.8 × 10-3) than for non-bitter taste genes (? =1.2-1.5 × 10-3). In addition, our results show that the difference in nutrient receptor genes between Asian and European breeds accounts for only a small part of the variability, which is in contrast with previous findings involving genome wide data. CONCLUSIONS: We have defined twenty-eight oral nutrient sensing related genes for the pig. The homology with the human repertoire is high for the porcine non-bitter taste gene repertoire and low for the porcine Tas2r repertoire. Our data suggests that bitter taste is a plastic trait, possibly associated with the ability of pigs to adapt to diverse environments and that may be subject to balancing selection.
Project description:Bitter taste perception likely evolved as a protective mechanism against the ingestion of harmful compounds in food. The evolution of the taste receptor type 2 (TAS2R) gene family, which encodes the chemoreceptors that are directly responsible for the detection of bitter compounds, has therefore been of considerable interest. Though TAS2R repertoires have been characterized for a number of species, to date the complement of TAS2Rs from just one bird, the chicken, which had a notably small number of TAS2Rs, has been established. Here, we used targeted mapping and genomic sequencing in the white-throated sparrow (Zonotrichia albicollis) and sample sequencing in other closely related birds to reconstruct the history of a TAS2R gene cluster physically linked to the break points of an evolutionary chromosomal rearrangement. In the white-throated sparrow, this TAS2R cluster encodes up to 18 functional bitter taste receptors and likely underwent a large expansion that predates and/or coincides with the radiation of the Emberizinae subfamily into the New World. In addition to signatures of gene birth-and-death evolution within this cluster, estimates of Ka/Ks for the songbird TAS2Rs were similar to those previously observed in mammals, including humans. Finally, comparison of the complete genomic sequence of the cluster from two common haplotypes in the white-throated sparrow revealed a number of nonsynonymous variants and differences in functional gene content within this species. These results suggest that interspecies and intraspecies genetic variability does exist in avian TAS2Rs and that these differences could contribute to variation in bitter taste perception in birds.
Project description:T2R (Tas2R) genes encode a family of G protein-coupled gustatory receptors, several involved in bitter taste perception. So far, few ligands for these receptors have been identified, and the specificity of most T2Rs is unclear. Differences between individual T2Rs result in altered taste perception in either specificity or sensitivity. All 33 human T2Rs are characterized by significant sequence homology. However, with a total of eight pseudogenes and >83 coding region single-nucleotide polymorphisms, the family displays broad diversity. The underlying variability of individual T2Rs might be the source for personalized taste perception. To test this hypothesis and also to identify T2Rs that possibly function beyond bitter taste, we compared all human T2R genes with those of the closely related primate species Pan paniscus (bonobo) and Pan troglodytes (chimpanzee). The differences identified range from large sequence alterations to nonsynonymous and synonymous changes of single base pairs. In contrast to olfactory receptors, no human-specific loss of the amount of functional genes was observed. Taken together, the results indicate ongoing evolutionary diversification of T2R receptors and a role for T2Rs in dietary adaptation and personalized food uptake.
Project description:Bitter taste perception, mediated by receptors encoded by the TAS2R loci, has important roles in human health and nutrition. Prior studies have demonstrated that nonsynonymous variation at site 516 in the coding exon of TAS2R16, a bitter taste receptor gene on chromosome 7, has been subject to positive selection and is strongly correlated with differences in sensitivity to salicin, a bitter anti-inflammatory compound, in human populations. However, a recent study suggested that the derived G-allele at rs702424 in the TAS2R16 promoter has also been the target of recent selection and may have an additional effect on the levels of salicin bitter taste perception. Here, we examined alleles at rs702424 for signatures of selection using Extended Haplotype Homozygosity (EHH) and FST statistics in diverse populations from West Central, Central and East Africa. We also performed a genotype-phenotype analysis of salicin sensitivity in a subset of 135 individuals from East Africa. Based on our data, we did not find evidence for positive selection at rs702424 in African populations, suggesting that nucleotide position 516 is likely the site under selection at TAS2R16. Moreover, we did not detect a significant association between rs702424 alleles and salicin bitter taste recognition, implying that this site does not contribute to salicin phenotypic variance. Overall, this study of African diversity provides further information regarding the genetic architecture and evolutionary history of a biologically-relevant trait in humans.