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Logo of nihpaAbout Author manuscriptsSubmit a manuscriptHHS Public Access; Author Manuscript; Accepted for publication in peer reviewed journal;
Annu Rev Nutr. Author manuscript; available in PMC 2009 August 5.
Published in final edited form as:
PMCID: PMC2721271

Taste Receptor Genes


In the past several years, tremendous progress has been achieved with the discovery and characterization of vertebrate taste receptors from the T1R and T2R families, which are involved in recognition of bitter, sweet, and umami taste stimuli. Individual differences in taste, at least in some cases, can be attributed to allelic variants of the T1R and T2R genes. Progress with understanding how T1R and T2R receptors interact with taste stimuli and with identifying their patterns of expression in taste cells sheds light on coding of taste information by the nervous system. Candidate mechanisms for detection of salts, acids, fat, complex carbohydrates, and water have also been proposed, but further studies are needed to prove their identity.

Keywords: gustatory, sweet, bitter, umami, salty, sour


The major focus of this review is on the mammalian taste receptors from the T1R and T2R families. We also briefly discuss other candidate taste receptors in mammals.

Taste System

In the common language, the word “taste” is often used to describe sensations arising from the oral cavity. However, the biological definition of taste, or gustation, is narrower and includes only sensations mediated by a specialized anatomically and physiologically defined chemosensory gustatory system. Along with taste sensations, food usually simultaneously evokes other sensations, e.g., odor, touch, temperature, and irritation. Although it is not always easy to separate all these sensations perceptually, the nongustatory components are sensed by different systems, olfaction and somatosensation.

The gustatory system in mammals includes taste receptor cells (TRCs) organized in taste buds located within gustatory papillae. Most of the taste papillae belong to three types—fungiform, foliate, and vallate—and are located in the tongue. There is also a substantial number of nonlingual taste papillae in the palate, oropharynx, larynx, epiglottis, and the upper esophagus. Apical ends of the TRCs are exposed to the oral cavity and interact with taste stimuli, usually water-soluble chemicals. This interaction generates signals that are transmitted to the brain via branches of three cranial nerves, VII (facial), IX (glossopharyngeal), and X (vagus). One branch of the VII nerve, the chorda tympani nerve, sends fibers to the anterior part of the tongue including fungiform papillae and possibly to the anterior portion of the foliate papillae. The other branch of the VII nerve, the greater petrosal nerve, sends fibers to the taste buds on the soft palate. Axons of the glossopharyngeal nerve innervate vallate and foliate papillae, and possibly taste buds in the pharynx. Axons of the vagus nerve innervate taste buds in the epiglottis, larynx, and the upper esophagus (170). These first-order ganglionic neurons terminate in the rostral part of nucleus of the solitary tract in the medulla. The upperorder projections from the nucleus of the solitary tract include parabrachial nucleus, thalamic taste area, insular-opecular (primary) taste cortex, caudolateral orbitofrontal (secondary) cortical taste area, amygdala, hypothalamus, and basal ganglia (144). This wide representation of taste information in the brain probably serves necessary to integrate it with interoceptive (hunger, satiety, specialized appetites) and exteroceptive (vision, olfaction, somatosensation) signals and to generate behavioral responses to taste stimuli. Central taste processing results in perception of several different aspects of taste: quality, intensity, hedonics (pleasantness or unpleasantness), location, and persistence.

Nutrition, Taste Reception, and Taste Receptors

The survival of all animals depends on consumption of nutrients. However, sources of nutrients often also contain toxic substances. Taste helps animals to decide whether a food is beneficial for them and should be consumed or whether it is dangerous for them and should be rejected. Probably, taste evolved to insure animals choose food appropriate for body needs.

The current consensus is that human taste sensations can be divided into five qualities: bitter, sour, salty, sweet, and umami (savory; the prototypical stimulus being the amino acid glutamate). Aversive bitter taste often indicates presence of toxins in food. Bitter and sour tastes may also signal spoiled food. The main salty taste stimuli are sodium salts, but some nonsodium salts also have a salty taste component. This suggests that salty taste signals the presence of either sodium or minerals in general. For some species, consummatory responses to salty taste stimuli differ widely between sodium-replete and-deplete animals. Concentrated salt solutions, which are aversive to sodium- or mineral-replete animals, can be palatable to animals with depletion. The most common natural sweet taste stimuli are sugars, which indicate the presence of carbohydrates in food. The most common umami taste stimulus is L-glutamate, which may indicate the presence of protein. Other important nutrients include lipids, calcium, and water, but the existence of taste qualities corresponding to them is debatable.

The existence of several different taste qualities implies that each taste quality has a specific coding mechanism mediated by specialized taste receptors. Current data support this hypothesis. Reception of taste qualities that humans describe as sweet, umami, and bitter involves proteins from the T1R and T2R families. Candidate receptors have been proposed for salty and sour tastes.

Traditionally, human sensations are used to describe the main five taste qualities. Although there are many studies showing that the mechanisms underlying perception of particular taste qualities are similar in human and nonhuman animals, applying terms for human sensations to nonhuman animals should be used with caution. It is more accurate to describe taste quality perception by nonhuman animals using chemical names of taste stimuli (e.g., sodium taste, or sucroselike taste), but for brevity we use in this review human descriptors for taste qualities.

What Are Taste Receptors?

Taste receptors function as chemoreceptors that interact with taste stimuli, or ligands, to initiate an afferent signal transmitted to the brain, which results in taste perception. Because many taste ligands do not easily permeate cell membranes, taste receptors are believed to be a part of the TRC membranes. Consistent with this belief, T1R and T2R receptors belong to a superfamily of G protein–coupled receptors (GPCRs) with characteristic seven domains spanning the plasma membrane. However, some other taste stimuli can penetrate cell membranes; these include sodium, protons, and some bitter and sweet compounds. These compounds may interact with intracellular targets to activate TRC, and therefore the definition of what would be a taste receptor for such ligands is less clear.

Although a number of proteins have been suggested to function as taste receptors, not all of them have been unanimously accepted as such. We believe that to prove that a molecule functions as a taste receptor, several criteria must be met: (a) the molecular identity of the candidate receptor should be established, (b) its expression in TRCs should be confirmed, (c) appropriate ligands should be identified, and (d) changes in taste function resulting from changes in the taste receptor should be demonstrated.

Nomenclature and Classification of Taste Receptor Genes and Proteins

Publications on taste receptors have a number of discrepancies in naming genes and proteins [e.g., see Supplemental Tables 1 and 2 (for all Supplemental Material, follow the Supplemental Material link from the Annual Reviews home page at]. This creates difficulties in comparing descriptions of the same gene that has different names in different publications. This situation is also common with other types of genes and may become especially confusing with large gene families present in multiple species, such as taste receptor genes. This problem resulted in attempts to unify gene and protein nomenclature (157).

The confusion with identification of taste receptor genes and proteins underscores the importance of following nomenclature rules. Guidelines for human, mouse, and rat gene nomenclature are accessible on the Internet (3, 5). For the two best-characterized families of taste receptors, T1R and T2R, standard gene names follow the following description: “taste receptor, type 1, member 1” (with corresponding type and member numbers). A corresponding gene symbol abbreviates this name to Tas1r1 (in mouse or rat) or TAS1R1 (in human); a corresponding protein symbol is T1R1 (uppercase letters and not italicized). For brevity, and especially when we refer to both human (TAS … R) and rodent (Tas … r) genes, we describe them as T … R genes. Besides differences in symbol letters (upper or lowercase), human and mouse T2R genes can also be distinguished by member number: The human genes have member numbers smaller than 100 (TAS2R1–TAS2R65), whereas the mouse genes have member numbers higher than 100 (Tas2r102–Tas2r146). Genes and proteins of other species can be distinguished by adding a lowercase letter indicating species, e.g., rTas2r123 for rat. Lists of human and mouse taste receptor genes, including their names, symbols, and synonyms, can be found in Supplemental Table 1 and 2, and can also be found in the human (2) and mouse (4) genome databases. A compilation of human and mouse T2R gene symbols, alternative symbols, and GenBank accession numbers is published in (7). An ultimate identifier of a gene is its nucleotide sequence, which should be used if gene identity is not certain.

Several classification systems have been proposed for the GPCR superfamily. One of the most frequently used includes GPCRs of different vertebrate and invertebrate species and groups them into six classes (clans): A, B, C, D, E, and F (1). According to this classification, T1Rs belong to class C (metabotropic glutamate/pheromone) GPCRs. T2Rs are described either as a separate putative family (1) or as distantly related to class A (rhodopsinlike) GPCRs (6). More recently, the GRAFTS (glutamaterhodopsin-adhesion-frizzled/taste2-secretin) classification system was developed based on phylogenetic analyses of transmembrane parts of human PCRs (58). According to this classification, T1Rs belong to the glutamate family. T2Rs form a distinct cluster within the frizzled/taste2 family; the second cluster of this family includes the frizzled receptors involved in cell proliferation and development.



The discovery of three mammalian T1R receptors resulted from two converging lines of studies. The first line was related to identification of a genetic locus that affects saccharin preference in mice (the Sac locus). In 1974, using long-term two-bottle tests, Fuller (60) showed that differences in saccharin preferences between the C57BL/6 and DBA/2 inbred strains largely depend on a single locus, Sac, with a dominant Sacb allele present in the C57BL/6 strain that was associated with higher saccharin preference and a recessive Sacd allele present in the DBA/2 strain that was associated with lower saccharin preference. Subsequent studies confirmed this finding in the BXD recombinant inbred strains, and in crosses between the C57BL/6 and DBA/2 and between the C57BL/6 and 129 strains (16, 23, 26, 113, 115, 133). In addition to sweetener preferences, the Sac genotype influenced the afferent responses of gustatory nerves to sweeteners (16, 98), which indicated that the Sac gene is involved in peripheral taste transduction and may encode a sweet taste receptor. The Sac locus has been mapped to the subtelomeric region of mouse chromosome 4 (16, 26, 115, 133).

The second line of studies stemmed from analyses of a taste-bud-enriched cDNA library (72), which resulted in a discovery of two putative G protein–coupled taste receptors, T1R1 and T1R2 (71). Localization of the Tas1r1 gene in the distal part of mouse chromosome 4, near the Sac locus, suggested that Tas1r1 and Sac were identical. However, a high-resolution genetic mapping study rejected this possibility by showing distinct locations for Tas1r1 and Sac (98). A positional cloning study at the Monell Chemical Senses Center has shown that the Sac locus corresponds to a novel gene, Tas1r3, which is the third member of the Tas1r family (14, 97, 137). These studies restricted the genomic position of the Sac locus to a critical interval not exceeding 194 kb and identified genes within this region. One of these genes, Tas1r3, was the most likely candidate for the Sac locus based on the effects of the Sac genotype on peripheral sweet taste responsiveness (16, 98) and the involvement of a G protein–coupled mechanism in sweet taste transduction (171). Tas1r3 sequence variants were associated with sweetener preference phenotypes in genealogically diverse mouse strains (14, 137). Substitution of Tas1r3 alleles in congenic mice resulted in phenotypical changes attributed to the Sac locus (14). These data provided evidence for the identity of Sac and Tas1r3 and for the role of the T1R3 receptor in sweet taste.

Several other studies provided additional evidence that Sac and Tas1r3 are identical:

  1. A phenotype rescue transgenic experiment, in which a genomic clone containing the Tas1r3 gene from the C57BL/6 mouse strain with a dominant Sac allele determining higher sweetener preference was incorporated in the genome of mice carrying a recessive Sac allele (from the 129X1/Sv strain) determining lower sweetener preference. The transgenic mice had higher taste preferences for sucrose and saccharin (but not for nonsweet taste solutions) compared with the 129X1/Sv mice (127).
  2. Genetically engineered mice lacking the Tas1r3 gene had diminished or abolished taste responses to sweeteners (46, 179).
  3. Cells with heterologously expressed T1R2 + T1R3 proteins responded to sucrose and saccharin more strongly when the C57BL/6 Tas1r3 allele was used compared with cell responses when 129X1/Sv Tas1r3 allele was used (126).
  4. An in vitro study (130) has shown that binding of several sweeteners to the extracellular N-terminal domain of the T1R3 protein was reduced when isoleucine at position 60 [a predicted sweetener-sensitive allele of the Sac/Tas1r3 gene (137)] was substituted to threonine (a predicted hyposensitive allele of the Sac/Tas1r3 gene).

Additional evidence that the three T1R proteins function as taste receptors included the demonstration that: (a) T1Rs are expressed in taste receptor cells (46, 71, 86, 91, 92, 99, 101, 107, 120, 123, 127, 137, 147); (b) cell cultures with heterologously expressed T1Rs respond to taste stimuli (100, 126, 127, 179); and (c) targeted mutations of the Tas1r genes affect taste responses of the genetically engineered mice (46, 179).

Genomic Organization

The three mouse Tas1r genes are located in the distal chromosome 4 in the order Tas1r2 (70.0 cM or 139 Mb, NCBI Build 36)—Tas1r1 (81.5 cM or 151 Mb)—Tas1r3 (83.0 cM or 155 Mb). Their human orthologs reside in a region of conserved synteny in the short arm of human chromosome 1 in the same order: TAS1R2 (1p36.13)—TAS1R1 (1p36.23)—TAS1R3 (1p36.33) (see Supplemental Figure 1).

The mouse Tas1r genes contain six coding exons (Supplemental Figure 2) and are translated into 842–858-amino acid proteins. The T1R proteins (Figure 1) have a predicted secondary structure that includes seven transmembrane helices forming a heptahelical domain and a large extracellular N-terminus composed of a Venus flytrap module and a cysteine-rich domain connected to the heptahelical domain (134). There is evidence for alternative splicing of the T1R1 (Supplemental Figure 3), T1R2 (123), and T1R3 (92, X. Li and D. Reed, unpublished data) genes.

Figure 1
Conformation of T1R and T2R proteins. Both T1R and T2R proteins are predicted to have seven transmembrane domains. The T1R proteins consist of ~850 amino acids and have a large extracellular N-terminus. The T2R proteins consist of ~300–330 amino ...

Tissue Expression

The main sites of expression of the T1R genes are TRC of the taste buds. In mice, rats, humans, pigs, and cats, the T1R3 gene is expressed in all types of taste buds (46, 91, 92, 99, 107, 120, 123, 127, 137, 147). Initial studies have shown that in mice and rats, the T1R1 gene is predominantly expressed in the fungiform and palate taste buds, is expressed in a smaller percentage of the foliate taste buds, and is rarely expressed in the circumvallate taste buds. The T1R2 gene is predominantly expressed in the circumvallate and foliate taste buds, is expressed in a smaller percentage of the palate taste buds, and is rarely expressed in the fungiform taste buds (71, 91, 123, 127). T1R1 and T1R2 are rarely coexpressed in the same TRC (71, 127). The T1R genes are not coexpressed with the T2R genes (127). In mice and rats, there are three main patterns of coexpression of the T1R genes in TRC: The first pattern is coexpression of T1R1 and T1R3 (in fungiform and palate taste buds), the second pattern is coexpression of T1R2 and T1R3 (in circumvallate, foliate and palate taste buds), and the third pattern is expression of only T1R3 (in fungiform and palate taste buds) (120, 123, 127).

Coexpression of T1R3 with either T1R1 or T1R2 in the same TRC suggested that they may function as heterodimers, which is believed to commonly occur with GPCRs (134). This pattern of coexpression also suggested that taste responses to sweeteners mediated by the T1R2 + T1R3 receptor combination should predominantly occur in the glossopharyngeal nerve that innervates the circumvallate taste buds, and that umami/L–amino acid taste responses mediated by the T1R1 + T1R3 receptor combination should predominantly occur in the chorda tympani nerve that innervates fungiform taste buds. However, this does not correspond to results of electrophysiological studies that show that both chorda tympani and glossopharyngeal nerves respond to sweet and umami taste stimuli (47, 74, 131, 132).

A subsequent study in mice has shown that TRCs in both fungiform and circumvallate papillae express each T1R receptor alone and in all possible combinations (T1R1 + T1R2, T1R1 + T1R3, T1R2 + T1R3, and T1R1 + T1R2 + T1R3) (86). Similarly, it was found that human fungiform taste buds express all three T1R genes, with some fungiform TRC coexpressing T1R2 and T1R3 (101). These results are in a better agreement with electrophysiological responsiveness of the chorda tympani and glossopharyngeal nerves. They also suggest the existence of T1R1 + T1R2 heterodimers and homodimers for each T1R receptor. Coexpression of the T1R1 and T2R genes in mice has also been reported (86).


T1R receptor-ligand interactions were characterized in two types of studies. In vitro heterologous expression experiments analyzed responses to taste stimuli in cells transfected with T1Rs. In vivo experiments examined effects of Tas1r genotypes on taste responses in mice. Two types of gene variation were studied in vivo: targeted mutations disrupting a gene (46, 179) and natural allelic variation (78) (these results are summarized in Supplemental Table 3).

Heterologously expressed T1R2 + T1R3 responds to a large number of sweeteners. The in vitro system reproduces in vivo species differences in sweet taste sensitivity. Several sweeteners (aspartame, cyclamate, neohesperidin dihydrochalcone, neotame, and sweet proteins) are perceived as sweet by humans but not rodents (e.g., 17, 48, 77). Correspondingly, human—but not rodent—T1R2 + T1R3 responds to these sweeteners. Heterologously expressed T1R1 + T1R3 functions as a broadly tuned L-amino acid receptor in mice and as a more narrowly tuned umami receptor in humans.

Experiments involving heterologous expression of combinations of T1Rs from different species (including interspecies receptor chimeras and receptors with mutations created at the interspecies variant sites) characterized the functional importance of different domains of T1R proteins. These studies have shown that human T1R1 determines higher T1R1 + T1R3 receptor selectivity for glutamate relative to the mouse receptor (126). Human T1R2 confers responsiveness of the T1R2 + T1R3 receptor to aspartame, glycyrrhizic acid, neotame, thaumatin, brazzein, and monellin (83, 126, 169, 179). The extracellular N-terminal domain of T1R2 is involved in recognition of aspartame (80, 176), neotame (176), D-tryptophan, and sucrose (80). The transmembrane domain of T1R2 is required for G-protein coupling of the T1R2 + T1R3 receptor (176). Responsiveness of the T1R2 + T1R3 receptor to cyclamate and neohesperidin dihydrochalcone, and its sensitivity to a sweet taste inhibitor lactisole, depend on the presence of human T1R3 (83, 178), specifically its transmembrane domain (81, 82, 169, 176). The cysteine-rich region of T1R3 is involved in recognition of brazzein and monellin (83).

For some ligands, interaction with both T1R2 and T1R3 receptor subunits has been demonstrated. Responsiveness to brazzein and monellin depends on interaction with both human T1R2 and human T1R3 (83). Binding assays have shown that N-terminal domains of mouse T1R2 and T1R3 bind sweeteners (glucose, sucrose, and sucralose), though with distinct affinities and conformational changes: Relative to T1R2, T1R3 binds sucrose with higher affinity and glucose with lower affinity (130).

Consistent with the in vitro results, Tas1r1 knockout mice are deficient in taste responses to L-amino acids and umami stimuli, Tas1r2 knockout mice are deficient in taste responses to sweeteners, and Tas1r3 knockout mice are deficient in taste responses to all these stimuli (46, 179). Variation of naturally occurring Tas1r3 alleles in inbred mouse strains (78) has a pattern of effects not completely identical to effects of Tas1r3 disruption in knockout mice. Tas1r3 allelic variation affects taste responses to sweeteners (including D-amino acids) but not to L-amino acids, nonchiral glycine, or umami taste stimuli. This pattern is more similar to changes found in Tas1r2 knockout mice. The likely reason for this is that the null allele of Tas1r3 prevents the formation of heteromeric receptors with both T1R1 and T1R2, thus affecting responses to all ligands of these receptors. Natural allelic variation of Tas1r3 affects binding affinity of the T1R3 protein for sweeteners (130), but it does not affect responses of heterologously expressed T1R1 + T1R3 to amino acids (126), which corresponds to effects of Tas1r3 polymorphisms in vivo. The lack of effect of the natural allelic variation of Tas1r3 on taste responses to ligands of the T1R1 + T1R3 receptor can be explained by several possible mechanisms: (a) ligand binding to the T1R3 receptor at a site that is not affected by the polymorphic variants, (b) ligand binding to the T1R1 receptor, or (c) the existence of another taste receptor binding these ligands.

In Tas1r2 and Tas1r3 knockout mice, concentrated solutions of sugars elicited reduced, but not completely eliminated, taste responses (46, 179). These residual responses were completely eliminated in Tas1r2/Tas1r3 double-knockout mice (179). This suggests that T1R2 and T1R3 may function on their own as low-affinity sugar receptors, probably as homodimers. Consistent with this hypothesis, heterologously expressed T1R3 alone responded to 0.5 M sucrose, but not to lower sucrose concentrations (<0.3 M) or to artificial sweeteners (179). Heterologously expressed T1R3 alone was also reported to respond to a sugar trehalose (8); however, another study reported that trehalose induced significant receptor-independent rises in Ca2+, and thus its use in a heterologous system was impractical (179). No responses to sweeteners were reported in cells with heterologously expressed T1R2 alone.

The data on ligand specificity of the T1R receptors suggest that perception of most of sweet and umami taste stimuli occurs via activation of these receptors. This is consistent with results of some human perception studies (31, 32). However, the existence of additional sweet or umami taste receptors is not precluded, and several candidates are described in a following section.

Allelic Variation of T1R Genes and Its Role in Individual Variation in Taste Responses

Within-species variation of the T1R genes has been examined in individual humans of different ethnicities and in strains of rats and mice. In rats and mice, the association of variants of the Tas1r3 gene with sweetener taste responses has been analyzed.


Humans differ in perception of sweet taste, but genetic determination of this variation has not been unequivocally established (138, 140). In humans of African, Asian, European, and Native American origin, all three TAS1R genes have multiple polymorphisms, which include those resulting in amino acid changes of T1R proteins and even in a premature stop codon in TAS1R1. The majority of amino acid sequence variation occurs in the N-terminus extracellular domain, where taste ligands are likely to bind the taste receptors. TAS1R2 was particularly diverse compared with other human genes: Its rate of polymorphisms was higher than average, in the top 5% to 10% of all human genes surveyed. Thus, TAS1R variation in human populations was predicted to contribute more to variation in sweet taste (which depends on TAS1R2 and TAS1R3) than to variation in umami taste (which depends on TAS1R1 and TAS1R3) (89).


Several rat strains with different saccharin preferences did not differ in protein sequence of T1R3. Some nonprotein-coding Tas1r3 variants found among these strains were not associated with marked differences in Tas1r3 expression and thus are unlikely to affect T1R3 function. Therefore, the prominent rat strain differences in saccharin preferences depend on genes other than Tas1r3 (107).


In initial studies that identified the mouse Tas1r3 gene, several polymorphisms associated with sweetener preferences were detected (91, 120, 123, 127, 147). However, these studies lacked proper quantitative analyses of gene-phenotype associations. Reed et al. (137) conducted a comprehensive quantitative analysis of the Tas1r3 sequence variants associated with saccharin preference using 30 genealogically diverse inbred mouse strains. Of the 89 polymorphisms detected within the ~6.7 kb genomic region including the Tas1r3 gene, eight were significantly associated with saccharin preferences. An absence of differences in the Tas1r3 gene expression in the taste tissues of mice with different Tas1r3 alleles suggested that the receptor function is likely to be affected by polymorphisms that change amino acid sequence of the T1R3 protein. A coding polymorphism with the strongest association with saccharin preferences resulted in the amino acid substitution of isoleucine to threonine at position 60 (I60T) in the extracellular N-terminus of the predicted T1R3 protein. Modeling of the T1R3 protein using the structure of the related mGluR1 receptor as a prototype has suggested that the I60T substitution introduces an extra N-terminal glycosylation site, which could affect dimerization of the receptor (120). However, this was not confirmed in a coimmunoprecipitation experiment (126). It was also suggested that this type of polymorphism could affect ligand binding (137). This prediction was subsequently confirmed in an in vitro study showing that a corresponding site-directed mutation changes binding affinity of the T1R3 protein to several sweeteners (130).

Other Candidate Receptors for Sweet and Umami Tastes

Several molecules have been proposed as candidate mammalian taste receptors for umami or glutamate taste, including splice variants of metabotropic glutamate receptors, mGluR4 and mGluR1, and the N-methyl-D-aspartatetype glutamate ion channel receptor (30, 39a, 148, 160). Some sweet-tasting compounds can penetrate TRC membrane and act on intracellular targets (125). Thus, these biological molecules may function as intracellular receptors of such compounds.



The existence of a family of bitter taste receptors was predicted more than ten years ago by I. Lush, a geneticist who studied mouse strain differences in bitter taste avoidance, and who suggested that a cluster of bitterness-tasting genes “have evolved from one original bitterness gene by a process of local duplication and differentiation” (115). The T2R genes were discovered in 2000 by two groups. These discoveries were based on analyses of the recently released human genome sequences in the genome regions linked to bitter taste responsiveness in humans and mice. Adler et al. (6) examined a region of human chromosome 5 linked to perception of a bitter compound 6-n-propyl-2-thiouracil (PROP) (139) and discovered a novel GPCR, TAS2R1. Similarity searches of genomic DNA revealed additional related genes in human chromosomes 7 and 12. Although the TAS2R1 gene is a candidate for the PROP sensitivity locus, which suggests that this is a bitter taste receptor for PROP, this relationship has not been experimentally proven yet, and T2R1 ligands are still not known. Matsunami et al. (118) examined a region of human chromosome 12 with conserved synteny to a region of mouse chromosome 6 containing the sucrose octaacetate aversion (Soa) locus (13, 36, 115) and discovered TAS2R genes based on their weak similarity to a vomeronasal receptor gene. Several subsequent publications have identified additional human, rat, and mouse TAS2R genes (42, 43, 174).

Genomic Organization

Current genomic databases (2, 4) list 43 human TAS2R genes (38 intact genes and 5 pseudogenes; Supplemental Table 1) on chromosomes 5, 7, and 12 (Supplemental Figure 1) and 40 mouse Tas2r genes (35 intact genes and 5 pseudogenes; Supplemental Table 2) on chromosomes 2, 6, and 15. The T2R genes are intronless (Supplemental Figure 2) and encode ~300–330 amino acid GPCR proteins with a short N-terminal extracellular domain (Figure 1).

Tissue Expression

The main sites of expression of the T2R genes in mammals are TRCs of the circumvallate, foliate, palate, and epiglottis taste buds, and to a lesser degree fungiform taste buds (6, 9, 21, 33, 34, 93, 118). In mammals, T2R and T1R genes are expressed in different subsets of TRC (127) (but see 86)

It appears that multiple T2Rs are co-expressed in the same TRC, and possibly nearly all T2Rs are expressed in each T2R-positive TRC (6). The largely overlapping expression of the T2R genes within individual TRCs has been confirmed in a transgenic “rescue” experiment. In bitter taste–deficient phospholipase Cβ2 (PLCβ2) knockout mice, PLCβ2 was reintroduced under the control of three different Tas2r gene promoters. Responsiveness to all bitter taste stimuli examined (presumably acting on different T2R receptors) was restored in each of the transgenic lines produced with different constructs (124). However, results of another study (118) suggested that different TRCs may express different T2Rs.

The pattern of T2R expression has implications for bitter taste coding. Coexpression of multiple T2Rs in the same TRCs (6, 124) is consistent with behavioral discrimination and generalization data in primates and rats suggesting an identical taste quality perception of different bitter compounds (10, 154) and with neurophysiological data showing that responses to different bitter taste stimuli activate similar groups of neurons in the rat nucleus of the solitary tract (37) and in the primate cortex (152). On the other hand, expression of different T2Rs in different TRCs (118) is consistent with neurophysiological data showing that different bitter taste stimuli activate different TRCs (35) and afferent peripheral gustatory neurons (45) in rats and with the lack of conditioned taste aversion generalization between some bitter taste stimuli in hamsters (56). These latter data suggest that the taste system can discriminate among different bitter taste stimuli. It was proposed that a discrepancy between expression of multiple T2Rs in the same TRC and selective responses of TRCs to bitter tastants might be due to differences in levels of expression of the same T2R in different TRCs. This would result in variation among individual T2R-expressing cells in their sensitivity to bitter tastants, although each of these TRCs still would respond to multiple bitter ligands (38).


The number of compounds perceived by humans as bitter (65) is much larger than the number of human TAS2R genes, implying that each human T2R responds to more than one bitter ligand (22). The same is likely to be true for other species. Some T2Rs interact with a wide range of bitter-tasting ligands (e.g., TAS2R14 and TAS2R16; see Supplemental Table 4), which supports this expectation. However, some other T2Rs appear to have narrow ligand specificities. It has been suggested that different T2R alleles may have different profiles of ligand specificity (87, 122). Thus, the repertoire of bitter taste receptors may be not limited by a number of the T2R genes, but may involve as many receptors as there are T2R alleles (122).

Ligands have been determined for only a relatively small number of T2Rs in four vertebrate species: humans, chimpanzees, rats, and mice (Supplemental Table 4). All of the compounds that interact with T2Rs evoke bitter taste sensation in humans. The T2R ligand specificities have been determined predominantly using in vitro studies. For the following six T2Rs, ligand specificity was examined both in vitro and in vivo with matching results, which provides compelling evidence that these T2Rs function as bitter taste receptors.

Mouse Tas2r105 gene is located in the genomic region of the Cyx (cycloheximide tasting) locus (11, 114) on distal chromosome 6.Tas2r105 coding sequence variants are associated with behavioral sensitivity to cycloheximide in several inbred mouse strains (39, 128). Cells heterologously expressing Tas2r105 respond to cycloheximide. Expression of a Tas2r105 allele from a cycloheximide taster strain results in higher cell responsiveness than does expression of an allele from a nontaster strain (39). Tas2r105 knockout mice show selective impairment in neural and behavioral responses to cycloheximide but not to other bitter or nonbitter taste stimuli (124).

Although these data provide strong evidence that the Tas2r105 gene is identical to the Cyx locus and encodes a receptor binding cycloheximide, some other data do not agree with this hypothesis. Chandrashekar et al. (39) examined strain distribution patterns of Tas2r105 genotypes and Cyx phenotypes in BXD recombinant inbred strains and found a tight linkage but not perfect concordance between these loci; they have explained this discordance by ambiguity in designation of the Cyx phenotype of the BXD strains by Lush & Holland (114). However, the study of Lush & Holland (114) has shown a clearly dichotomous strain distribution pattern of the BXD strains. But, strangely, the progenitors of the BXD strains had similar responsiveness to cycloheximide: The average preference scores for 1 µM cycloheximide were 22% in the C57BL/6 inbred strain and 29% for the DBA/2 strain. Both progenitor strains were similar to a group of BXD strains that formed a cluster of sensitive strains with an average preference score for 1 µM cycloheximide of 18%, as opposed to a group of relatively insensitive BXD strains with an average preference score 41% (114). Consistent with these data, no differences were found between C57BL/6 and DBA/2 strains in brief-access responses to cycloheximide in a recent study (29). In addition, preference scores for cycloheximide were continuously distributed among 27 inbred strains (114), which does not allow them to be categorized as tasters and nontasters. Thus, analysis of Tas2r105 sequence variants between strains assumed to be tasters (CBA/Ca, BALB/c, C3H/He, and DBA/2) and nontasters (C57BL/6 and 129/Sv) (39) is questionable. An additional limitation of this analysis is that the four taster strains have shared genealogy (20) and thus are likely to share many parts of the genome due to identity-by-descent, and not necessarily because of a true genotype-phenotype association. These inconsistencies require additional studies to resolve. A quantitative analysis of genotype-phenotype associations in genealogically diverse strains (e.g., 137) would provide more conclusive data.

Orthologous human TAS2R4 and mouse Tas2r108 respond to denatonium and PROP in a heterologous system (39). Transgenic expression of each gene in the chemosensory neurons of Caenorhabditis elegans affected behavioral responses of worms to denatonium and PROP (44).

Human TAS2R16 responds to β-glucopyranosides in the heterologous expression system (34). Naturally occurring human TAS2R16 alleles have different responsiveness to several β-glucopyranosides in vitro (69, 153). It is unknown whether these alleles are also associated with human perception of β-glucopyranoside bitterness. Although wild-type mice are indifferent to phenyl-β-D-glucopyranoside, mice with a human TAS2R16 transgene expressed in bitter-sensing cells under control of the mouse Tas2r119 promoter avoid phenyl-β-D-glucopyranoside in behavioral tests. Mice with human TAS2R16 transgene expressed in sweet-sensing cells under control of the mouse Tas1r2 promoter show preference for phenyl-β-D-glucopyranoside (124). Transgenic expression of human TAS2R16 in the chemosensory neurons of C. elegans affected behavioral responses of worms to phenyl-β-D-glucopyranoside (44).

Human TAS2R38 was demonstrated in a positional cloning study (88) as a gene identical to a human phenylthiocarbamide (PTC) bitter taste sensitivity locus on chromosome 7q (50). TAS2R38 has three common missense single nucleotide polymorphisms resulting in substitutions of proline to alanine at amino acid position 49 (P49A), alanine to valine at position 262 (A262V), and valine to isoleucine at position 296 (V296I). These polymorphisms give rise to several haplotypes, the most common of which are PAV (PTC-sensitive allele) and AVI (PTC-insensitive allele) (88, 173). TAS2R38 genotypes are associated with human perception of PTC and PROP bitterness (33, 52, 121, 135). Cells heterologously expressing the sensitive PAV alleles of TAS2R38 respond to thioamides (including PTC and PROP). PTC and PROP responses of cells heterologously expressing different alleles of TAS2R38 correlate with psychophysical responses of individuals carrying these alleles (33). Although wild-type mice do not show strong lick suppression in response to PTC solutions in brief-access tests (128), mice with a taster (PAV) allele of human TAS2R38 transgenically expressed in bitter-sensing cells under the control of a mouse Tas2r promoter show strong aversion to PTC (124).

Although a PTC nontaster allele of human TAS2R38 (AVI) is expressed in taste buds, it does not respond to taste stimuli in vitro (33). Because taster and nontaster alleles of TAS2R38 are maintained by balanced selection (173), it was suggested that the nontaster allele may serve as a receptor for as yet unidentified toxic bitter substances other than PTC (87, 173).

Allelic variants of chimpanzee TAS2R38, an ortholog of human TAS2R38, are also associated with taste sensitivity to PTC in individual animals. A taster allele of chimpanzee TAS2R38 responds to PTC in vitro (172).

Allelic Variation of T2R Genes and Its Role in Individual Variation in Taste Responses


Individual humans differ in bitter taste perception, and some of this variation has a genetic component (140). Human TAS2R genes have substantial diversity of coding sequence (87, 122, 161, 167), which suggests that TAS2R polymorphisms may be responsible for the genetic component of individual differences in bitter taste.

However, this relationship has been demonstrated only for one gene, TAS2R38. It is located on chromosome 7, where linkages for PTC and PROP taste sensitivity have been detected (40, 41, 50, 135, 139). Allelic variants of TAS2R38 explain more than 50% of phenotypical variation in PTC sensitivity (88) and are also associated with human perception of PROP bitterness (33, 52, 121, 135).

Significant or suggestive linkages have been also detected on chromosomes 1, 3, 10, and 16 for PTC taste sensitivity (50) and on chromosome 5 for PROP taste sensitivity (139). The PROP sensitivity locus on human chromosome 5 (139) includes the TAS2R1 gene but no other TAS2R genes. However, the identity of the PROP sensitivity locus and the TAS2R1 gene has not yet been proven. The PTC sensitivity loci in chromosomes 1, 3, 10, and 16 (50) contain no TAS2R genes. Identification of genes corresponding to the genetic loci for bitter taste sensitivity, and matching variation in TAS2R sequences with individual variation in bitter taste perception, are important areas for future studies.

Hamsters, rats, and mice

Strain differences in behavioral responses to bitter taste stimuli were found in rats (159) and hamsters (57), but most research on genetics of taste has been conducted in mice. Mouse strains differ in behavioral and neural responses to bitter taste stimuli (e.g., 27, 29, 76, 108112, 114). Several linked genetic loci on mouse chromosome 6, in a Tas2r gene–cluster region, are responsible for variation in aversion to bitter-tasting quinine (Qui), cycloheximide (Cyx), copper glycinate (Glb), and acetylated sugars, sucrose octaacetate and raffinose undecaacetate (Soa/Rua) (11, 13, 26, 36, 66, 67, 76, 108, 110, 112, 114, 115, 129, 168).

A few studies conducted so far have detected considerable variation in sequences of the mouse Tas2r genes (39, 128, 129). All this strongly suggests that the genetic variation in taste responses to the bitter compounds is due to polymorphisms of the Tas2r genes, as was predicted by Lush et al. (115). However, this relationship has been demonstrated only for the Tas2r105 gene corresponding to the Cyx locus (39, 124, 128), although with some inconsistencies (see Ligands section, above). There is also evidence for additional linkages of mouse bitter taste responses outside the Tas2r regions (68, 95, 129).

Other Candidate Receptors for Bitter Taste

In addition to activation of T2R receptor proteins, some bitter compounds can interact with ion channels in the cell membrane or with intracellular targets (125, 145, 150). Thus, these proteins may also function as receptors for these compounds.


Candidate Sour Taste Receptors

A commonly accepted view is that the taste receptors for sour (H+) and salty (Na+) tastes are ion channels (25, 49). Several candidate sour (acid) taste receptors have been proposed in recent years. One of these genes is a neuronal (degenerin) amiloride-sensitive cation channel 1 (see ACCN1 sidebar). It has been proposed as a sour taste receptor in rat (102, 105, 162164). However, this channel is not expressed in mouse taste buds (143), and behavioral (90) and physiological (143) responses to sour taste stimuli are unaltered in mice lacking the Accn1 gene. HCN1 and HCN4, members of a family of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels (see HCN sidebar), were also proposed as putative sour receptors (156). However, Ca2+ responses of taste cells to acids were not inhibited by Cs+, an inhibitor of HCN channels (141). Acid taste transduction involves intracellular acidification of TRC (116, 141), which is expected to affect acid-sensitive ion channel(s). Several two-pore domain potassium leak conductance channels from the K2P family are sensitive to intracellular acidification and thus were examined as candidate acid taste transducers. Based on the gene expression pattern and pharmacological analysis, TASK-1 appears to be the most likely candidate (see TASK-1 sidebar), although other K2P channels cannot be excluded (142). The Na+-H+-exchanger isoform 1 (NHE-1) (see NHE-1 sidebar) was also suggested to be involved in sour taste transduction based on its gene expression and pharmacological analyses (165).


In humans, the neuronal (degenerin) amiloride-sensitive cation channel 1 is encoded by the ACCN1 gene on chromosome 17q11 [gene name: amiloride-sensitive cation channel 1, neuronal (degenerin); other symbols: ACCN, ASIC2a, ASIC2, BNC1, BNaC1, hBNaC1 and MDEG]. In the mouse, it is encoded by the Accn1 gene on chromosome 11 [gene name: amiloride-sensitive cation channel 1, neuronal (degenerin); other symbols: ASIC2, BNaC1a, BNC1, Mdeg]. Accn1 is a member of a family of voltage-insensitive cation channels involved in mechanosensitivity and acid sensitivity. Its mRNA exists as two splice variants, described as ASIC2a and ASIC2b (166).


The human HCN1 gene is on chromosome 5p12 (gene name: hyperpolarization activated cyclic nucleotide-gated potassium channel 1; other names: BCNG1, BCNG-1, HAC-2). The mouse Hcn1 gene is on chromosome 13 (gene name: hyperpolarization-activated, cyclic nucleotide-gated K+ 1; other names: Bcng1s, HAC2). The human HCN4 gene is on chromosome 15q24 (gene name: hyperpolarization activated cyclic nucleotide-gated potassium channel 4). The mouse Hcn4 gene is on chromosome 9 (gene name: hyperpolarization-activated, cyclic nucleotide-gated K+ 4).


In humans, the TASK-1 channel protein is encoded by the KCNK3 gene on chromosome 2p23 (gene name: potassium channel, subfamily K, member 3; other names: TASK, TASK-1). Its mouse ortholog is Kcnk3 on chromosome 5 (gene name: potassium channel, subfamily K, member 3; other names: cTBAK-1).


In humans, the NHE-1 protein is encoded by the SLC9A1 gene on chromosome 1p36 [gene name: solute carrier family 9 (sodium/hydrogen exchanger), member 1 (antiporter, Na+/H+, amiloride sensitive); other symbols: APNH, NHE1]. Its mouse ortholog is Slc9a1 on chromosome 4 [gene name: solute carrier family 9 (sodium/hydrogen exchanger), member 1; other symbols: antiporter, Apnh, Na+/H+, amiloride sensitive, Nhe1].

Finally, the most recent studies suggest that the Pkd1l3 and Pkd2l1 genes (see PKD1L3 and PKD2L1 sidebar) participate in reception of sourness (73, 79, 106). However, their role in behavioral taste responses to sourness has not yet been demonstrated. In addition, some questions arising from the most recent studies have not been resolved. For example, acids activate the Pdk2l1 protein in vitro only when it is coexpressed with Pkd1l3 (79). Yet, disruption of Pdk2l1-expressing cells in the fungiform papillae abolishes CT responses to acids (73) despite lack of Pkd1l3 expression in these cells (73,79). This suggests the existence of another, yet unknown partner for heteromerization with Pdk2l1.


The human PKD1L3 gene is on chromosome 16q22 (gene name: polycystic kidney disease 1-like 3); its mouse ortholog is Pkd1l3 on chromosome 8 (gene name: polycystic kidney disease 1 like 3). The human PKD2L1 gene is on chromosome 10q24 (gene name: polycystic kidney disease 2-like 1; other symbols: PKD2L, PKDL). Its mouse ortholog is Pkd2l1 on chromosome 19 (gene name: polycystic kidney disease 2-like 1; other symbols: PCL, PKD2L, Pkdl, polycystin-L, TRPP3).

Candidate Salty Taste Receptors

A large number of studies suggested that at least in rodents, Na+ taste reception involves the selective epithelial amiloride-sensitive sodium channel, ENaC, which is a member of the degenerin/ENaC superfamily of ion channels (for reviews, see 28, 103). In humans, there are four ENaC channel subunits, α, β, γ, and δ. Mice and rats lack the ENaC δ subunit (85) (see ENaC sidebar). A variant of a vanilloid (capsaicin) receptor-1 has been proposed as an amiloride-insensitive salt taste receptor in rodents (117) (see TRPV1 sidebar). However, the evidence for ENaC or other candidate salt taste receptors in vertebrate is not as convincing as it is for the T1R and T2R receptors. The strongest evidence for involvement of degenerin/ENaC channel genes in Na+ taste responses was found for the ppk11 and ppk19 genes in Drosophila (104).


The four human ENaC channel subunits, α, β, γ, and δ, are encoded respectively by four genes: SCNN1A (alias: ENaCa) on chromosome 12p13, closely linked SCNN1B (alias: ENaCb) and SCNN1G (alias: ENaCg) on chromosome 16p12, and SCNN1D (aliases: dNaCh, ENaCd) on chromosome 1p36 (gene names: sodium channel, nonvoltage-gated 1 alpha, beta, gamma, or delta; SCNN1B is also known as a gene responsible for Liddle syndrome). The three mouse ENaC channel subunits, α, β, and γ, are encoded respectively by three genes: Scnn1a on chromosome 6, and closely linked Scnn1b and Scnn1g on chromosome 7 (gene names: sodium channel, nonvoltage-gated, type I, alpha, beta, or gamma).


Human vanilloid receptor-1 is encoded by the TRPV1 gene on chromosome 17p13 (gene name: transient receptor potential cation channel, subfamily V, member 1; previous name: vanilloid receptor subtype 1; previous symbol: VR1). Its mouse ortholog is Trpv1 on chromosome 11 (gene name: transient receptor potential cation channel, subfamily V, member 1; other names: capsaicin receptor, OTRPC1, VR-1).

Taste Detection of Lipids

The predominant orosensory cue for fat itself is its texture (119). Fat may also be detected by the presence of its decomposition products or impurities (136), which can activate olfactory or gustatory systems. Recent data suggest that taste may play a more important role in detection of dietary lipids than was previously believed. Dietary lipids consist mainly of triglycerides, but the lingual lipase hydrolyzes triglycerides and releases free fatty acids in the oral cavity where they can access TRCs and affect their function. Free fatty acids were shown to inhibit the delayed rectifying potassium channels in rat TRCs (63). In addition, the fatty acid transporter CD36 is expressed in TRCs and may be involved in oral detection of fatty acids (59, 94, 177) (see CD36 sidebar).


Human CD36 gene is on chromosome 7q11 (gene name: CD36 molecule; previous names: CD36 antigen, collagen type I receptor, thrombospondin receptor; other symbols: SCARB3, GPIV, FAT, GP4, GP3B). Its mouse ortholog is Cd36 on chromosome 5 (gene name: CD36 antigen; other symbols: FAT, fatty acid translocase, Scarb3).

Taste Detection of Complex Carbohydrates

Rats and some other species may also perceive a taste of polysaccharides and starch, which is qualitatively distinct from the taste of sugars (151). A molecular mechanism of gustatory reception of these complex carbohydrates is unknown, but there is evidence that it does not involve the T1R3 receptor (75).

Taste Detection of Water

Water consumption is crucial for animals’ survival and is regulated by thirst, a specialized water appetite. This suggests that animals have mechanisms for chemosensory detection of water or hypo-osmotic fluids. Consistent with this, water can evoke taste responses (62). It was suggested that TRCs act as osmotic sensors and that transduction of hypoosmotic stimuli involves water influx through aquaporins followed by activation of volume-regulated anion channels (62). Several aquaporin molecules are expressed in TRC, with the apically expressed AQP5 being the most likely candidate for water taste transduction (62, 64) (see AQP5 sidebar).


Human AQP5 gene is on chromosome 12q13 (gene name: aquaporin 5); its mouse ortholog is Aqp5 on chromosome 15 (gene name: aquaporin 5).

Taste perception of water by humans largely depends on the adaptation state of the oral cavity. Adaptation to different taste solutions (and probably to saliva) affects how water is perceived (18). Water elicits a strong sweet taste when it is applied to the oral cavity after exposure to sweet taste blockers. This phenomenon has been labeled “sweet water after-taste” (51). This adaptation-dependent perception of water taste could involve central mechanisms, intracellular adaptation within TRC, or interactions at the receptor level. A recent in vitro study with a heterologously expressed T1R2 + T1R3 receptor demonstrated that sweet water aftertaste is explained by interactions at the receptor level. This study suggested that the sweet taste receptor shifts from an inactive state (when it is exposed to a sweet taste inhibitor) to an active state (upon rinsing with water), which initiates transduction events and results in perception of sweetness (61).


Some substances detected by the gustatory system as taste stimuli also need to be detected inside the body for homeostatic regulation. There are interoceptive mechanisms for detecting sodium, pH, glucose, and amino acids in different internal organs, such as the kidney, pancreas, gut, and brain. This raises the possibility that the same receptors can serve as taste receptors and interoceptors. Although in some cases taste and interoception use different receptor mechanisms [e.g., for detection of glucose and sodium by brain (70, 96)], there are examples of sharing the same receptor protein by the two systems. The Pkd2l1 channel is involved in pH sensing by the TRC and by neurons in the spinal cord (73). ENaC may also be a shared mechanism for sodium detection by TRC and other body tissues.

A number of studies have detected expression of the T1R and T2R genes in nontaste tissues. The T1R genes were found in testis (91, 92, 120), brain, thymus (120), gastrointestinal tract, enteroendocrine cells (24, 53, 120, 146), kidney, lymphocytes (92), liver, and pancreas (158). The T2R genes were found in testis (118), gastrointestinal tract, enteroendocrine cells (146, 174, 175), and nasal respiratory epithelium (55). This suggests that the taste receptors may be involved in the chemosensory function of these organs (155).

Ectopic expression of olfactory receptor genes similarly has raised questions about the role they play in nonolfactory tissues. A recent systematic analysis of olfactory receptor expression in different tissues suggested that only small olfactory receptor subsets might play functional roles in different tissues, while most of them are likely to be under a neutral transcription control (54). Similarly, caution should be exerted when offering a functional interpretation for ectopic expression of taste receptors until more comprehensive studies are conducted.


There is substantial interest in developing novel taste stimuli and taste modifiers for humans and other animals. For humans, areas of interest include making food and drinks healthier without sacrificing their palatability and making oral medications more acceptable to patients. A substantial demand exists for artificial sweet and umami compounds, enhancers of salty, sweet, and umami taste, blockers of bitter taste, and pharmaceutical compounds with improved sensory properties. There is also a demand for improvement in the taste quality of food for companion and farm animals and for developing nonlethal repellents of wild animals, e.g., nontoxic chemicals with aversive taste. Development of such products has been hampered by lack of knowledge of the molecular identity of the taste receptors. Discovery of taste receptors, characterization of their active sites involved in interactions with agonists and antagonists, and development of high-throughput techniques for in vitro screening of taste stimuli will facilitate the design of novel taste-active compounds.

Allelic variation of human taste receptors can affect food perception, choice, and consumption. As a result, it can influence nutrition and potentially predispose individuals to certain diseases (e.g., 19). Thus, some taste receptor alleles can be disease risk factors. Genotypes of these receptors may be useful as biological markers to identify predispositions to some diseases and to suggest interventions for disease prevention. Available data provide some examples for the role of taste receptor variation in human nutrition and health.

Sensitive alleles of human TAS2R38 receptor respond to PTC, PROP, and related compounds that contain a thiourea (N - C = S) moiety. Some plants consumed by humans contain glucosinolates, compounds that also contain the thiourea moiety. A recent study has shown that TAS2R38 genotype affects perception of bitterness of glucosinolate-containing plants, such as broccoli, turnip, and horseradish (149). Allelic variation of TAS2R38 may have even more widespread effects on food choice, as it was shown to be associated with preferences for sucrose and sweet-tasting beverages and foods in children (but not adults) (121).

Taste receptor variation may be a biomarker of predisposition to alcoholism. Ethanol flavor has bitter and sweet taste components. Variation in bitter and sweet taste responsiveness is associated with perception of ethanol flavor and consumption of alcoholic beverages (12). In mice, allelic variation of the Tas1r3 sweet taste receptor gene is associated with voluntary ethanol consumption (15). Although hedonic responses to sweet taste are considered as one of the biomarkers of predisposition to alcoholism in humans (84), genes responsible for this association are still unknown. Higher sensitivity to ethanol bitterness may protect against excess alcohol consumption. Consistent with this hypothesis, individuals carrying one or two sensitive (PAV) alleles of the PTC receptor gene, TAS2R38, had lower yearly consumption of alcoholic beverages than did individuals homozygous for the insensitive allele, AVI (52). Similarly, there is an association between risk of alcohol dependence and TAS2R16 (β-glucopyranosides receptor) polymorphisms: An ancestral K172 allele, which is less sensitive to β-glucopyranosides in vitro, is associated with increased risk of alcohol dependence (69).


Taste receptors function as one of the interfaces between internal and external milieus. Tremendous progress has been achieved in the past few years with the discovery of the T1R and T2R receptors and the understanding of their function. Individual differences in taste, at least in some cases, can be attributed to allelic variants of the taste receptor genes. Understanding how taste receptors interact with taste stimuli and identifying their patterns of expression in taste cells shed light on coding of taste information by the nervous system.

However, many challenging tasks remain before we fully understand how taste works. Much of this important future research must be done with taste receptor genes. The important questions to be addressed include finding genes that encode a complete repertoire of taste receptors for different taste qualities, as well as genes that encode proteins involved in taste transduction and transmission, taste bud cell turnover, and connectivity between taste cells and afferent nerves. Studies of allelic variation of taste receptors will help to elucidate individual differences in taste perception, food choice, nutrition, and health, and to understand functional organization of receptor domains and their ligand specificities.

Supplementary Material



Research by the authors is supported by NIH grants R01DC00882 and R01AA11028 and an Ajinomoto Amino Acid Research Program Focused Research grant.


taste receptor cell
G protein-coupled receptor
phospholipase Cβ2


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