Genetics of Taste Perception

Abstract

There is considerable genetic variation in taste perception within and among species. Some taste perception phenotypes have simple monogenic inheritance, whereas others have complex genetic architecture. Recent advances with genomic resources have made genetics a powerful approach to identify taste‐related genes. Chromosomal mapping and positional cloning studies facilitated discovery of taste receptors. The genetic mapping and candidate gene association studies show that taste perception phenotypes are influenced by allelic variation of genes involved in both peripheral and central taste processing. Sequence variation of taste receptor genes explains some species differences in taste perception and sheds light on evolution of ingestive behaviour. Genetic variation in taste perception impacts human nutrition and health and may be useful as a biomarker of predisposition to some diseases. Identification of genes responsible for within‐ and between‐species variation in taste can provide tools to better control food choice and intake in humans and other animals.

Key Concepts:

  • Genes contribute to individual variation in perception of each of the five primary taste qualities: bitter, sweet, umami, salty and sour.

  • Genetic variation in taste perception involves polymorphisms of taste receptors, genes involved in peripheral taste transduction and central taste processing.

  • Genetic variation in taste perception impacts human nutrition and health and could be used as a biomarker of predisposition to some diseases.

Keywords: taste; gustatory; bitter; sweet; umami; salty; sour; behaviour; perception; genetics

Figure 1.

Taste receptors. The T1R (a) and T2R (b) proteins have seven transmembrane domains and are G protein‐coupled receptors, whereas ENaC (c) is an ion channel. (a) The T1R proteins consist of ∼850 amino acids and have a large extracellular N‐terminus composed of a Venus Flytrap module and a cysteine‐rich domain connected to the heptahelical domain. In humans and most mammalian species, this family includes three proteins: T1R1, T1R2 and T1R3. Their corresponding gene symbols are TAS1R1, TAS1R2 and TAS1R3 (in humans), and Tas1r1, Tas1r2 and Tas1r3 (in other species). Numbers of the T1R genes in different vertebrate species range from complete absence in the frog to five in some fishes (Boughter and Bachmanov, ). A T1R2+3 heterodimer functions as a sweet taste receptor. A T1R1+3 heterodimer functions as an umami taste receptor in humans, and is more broadly tuned l‐amino acid taste receptor in rodents. (b) The T2R proteins consist of ∼300–330 amino acids and have a short extracellular N‐terminus. Their corresponding gene symbols are TAS2R (in humans), and Tas2r (in other species). Number of the Tas2r genes in vertebrate species with sequenced genomes varies widely (Boughter and Bachmanov, ). Many species in addition to functional Tas2r genes have pseudogenes. For example humans, according to different sources, have 25–38 intact genes and 5–16 pseudogenes. Over half of human T2Rs have been de‐orphanised, mainly through the use of heterologous cell assays, and in all cases ligands were bitter‐tasting compounds. Several T2Rs are broadly tuned to detect stimuli of different chemical classes, whereas others appear more specific, activated by one or a couple of agonists. Multiple T2Rs are co‐expressed in the same taste receptor cell. As a result, a single T2R‐expressing cell can respond to different bitter taste compounds. (c) The epithelial sodium channel, ENaC, is a member of the degenerin/ENaC superfamily of ion channels. The ENaC channel is a heteromer consisting of several different subunits: α, β, γ and/or δ. Each ENaC subunit has two transmembrane domains and is encoded by a separate gene. In humans, there are four ENaC channel subunits, α, β, γ and δ (encoded by the nonvoltage‐gated sodium channel 1 genes SCNN1A, SCNN1B, SCNN1G and SCNN1D, respectively). Mice and rats lack ENaCδ subunit and therefore have only three ENaC subunits encoded by the Scnn1a, Scnn1b and Scnn1g genes. ENaC is involved in transepithelial ion transport in many tissues (kidney, lung, etc.). Because in some species sodium taste responses are suppressed by amiloride, a diuretic that inhibits the ENaC channel, ENaC was proposed as a candidate salty taste receptor. Recent work with mice genetically engineered to lack ENaC in taste cells (Bosak et al., ; Chandrashekar et al., ) has confirmed the importance of this channel in mediating sodium taste in mice.

Figure 2.

Variation in sweet‐liking in humans. Individual hedonic ratings of sucrose. ‘Likers’ report an increase in pleasantness with increasing sucrose concentration, ‘dislikers’ report a decrease in pleasantness at higher concentrations, and ‘neutrals’ have a minimal affective response to all concentrations. A schematic diagram drawn from data presented in Looy and Weingarten ; reproduced by permission of the Oxford University Press.

Figure 3.

Positional cloning of the Sac (saccharin preference) locus. (a) Linkage map of mouse distal chromosome 4 based on data from the F2 intercross between C57BL/6ByJ and 129P3/J inbred strains. The X‐axis shows distances between markers in recombination units (cM). The Y‐axis shows the logarithm of the odds ratio (LOD) scores for sucrose and saccharin consumption. The LOD score peaks (indicated by black triangles) and confidence intervals (solid horizontal line for sucrose, and dotted horizontal line for saccharin) define the ∼5 cM genomic region of the Sac locus. (b) Linkage map of the Sac‐containing region defined based on the size of the donor fragment in the 129.B6‐Sac congenic strain (black box). Distances between markers were estimated based on the B6×129 F2 intercross (see panel a). The Sac locus was mapped to a 0.7 cM interval corresponding to the congenic donor fragment. (c) A contig of bacterial artificial chromosome (BAC) clones and physical map of the Sac region. BAC clones are represented by horizontal lines. Dots indicate marker content of the BAC clones. Physical mapping determined that the 0.7‐cM congenic donor fragment has the physical size of 194 kb. A BAC clone encompassing the donor fragment was sequenced, and the DNA sequence was analysed for gene content (d). (d) Genes within the Sac‐containing interval. Filled areas indicate 12 predicted genes. Arrows indicate the predicted direction of transcription. The Tas1r3 gene encoding a G protein‐coupled receptor was the most likely candidate for the Sac locus. Reproduced in a modified form from (Bachmanov et al., ) by permission of the Oxford University Press.

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References

Bachmanov AA, Bosak NP, Floriano WB et al. (2011) Genetics of sweet taste preferences. Flavour and Fragrance Journal 26(4): 286–294.

Bachmanov AA, Inoue M, Ji H et al. (2009) Glutamate taste and appetite in laboratory mice: physiologic and genetic analyses. American Journal of Clinical Nutrition 90(3): 756S–763S.

Bachmanov AA, Li X, Li S et al. (2001a) High‐resolution genetic mapping of the sucrose octaacetate taste aversion (Soa) locus on mouse Chromosome 6. Mammalian Genome 12(9): 695–699.

Bachmanov AA, Li X, Reed DR et al. (2001b) Positional cloning of the mouse saccharin preference (Sac) locus. Chemical Senses 26(7): 925–933.

Bosak N, Inoue M, Nelson T et al. (2010) Epithelial sodium channel (ENaC) is involved in reception of sodium taste: evidence from mice with a tissue‐specific conditional targeted mutation of the ENaCa gene (Abstract). AChemS XXXII Annual Meeting; 21–25 April 2010; St. Petersburg (FL). Chemical Senses 35. doi:10.1093/chemse/bjq1071.

Boughter JD and Bachmanov AA (2008) Genetics and evolution of taste. In: Firestein S and Beauchamp GK (eds) Olfaction and Taste, pp. 371–390. San Diego: Elsevier/Academic Press.

Chandrashekar J, Kuhn C, Oka Y et al. (2010) The cells and peripheral representation of sodium taste in mice. Nature 464(7286): 297–301.

Chandrashekar J, Mueller KL, Hoon MA et al. (2000) T2Rs function as bitter taste receptors. Cell 100(6): 703–711.

Chen QY, Alarcon S, Tharp A et al. (2009) Perceptual variation in umami taste and polymorphisms in TAS1R taste receptor genes. American Journal of Clinical Nutrition 90(3): 770S–779S.

Damak S, Rong M, Yasumatsu K et al. (2006) Trpm5 null mice respond to bitter, sweet, and umami compounds. Chemical Senses 31(3): 253–264.

Dong D, Jones G and Zhang S (2009) Dynamic evolution of bitter taste receptor genes in vertebrates. BMC Evolutionary Biology 9: 12.

Eny KM, Corey PN and El‐Sohemy A (2009) Dopamine D2 receptor genotype (C957T) and habitual consumption of sugars in a free‐living population of men and women. Journal of Nutrigenetics and Nutrigenomics 2(4–5): 235–242.

Eny KM, Wolever TM, Corey PN et al. (2010) Genetic variation in TAS1R2 (Ile191Val) is associated with consumption of sugars in overweight and obese individuals in 2 distinct populations. American Journal of Clinical Nutrition 92(6): 1501–1510.

Eny KM, Wolever TM, Fontaine‐Bisson B et al. (2008) Genetic variant in the glucose transporter type 2 is associated with higher intakes of sugars in two distinct populations. Physiological Genomics 33(3): 355–360.

Fushan AA, Simons CT, Slack JP et al. (2009) Allelic polymorphism within the TAS1R3 promoter is associated with human taste sensitivity to sucrose. Current Biology 19(15): 1288–1293.

Fushan AA, Simons CT, Slack JP et al. (2010) Association between common variation in genes encoding sweet taste signaling components and human sucrose perception. Chemical Senses 35(7): 579–592.

Glendinning JI (1994) Is the bitter rejection response always adaptive? Physiology & Behaviour 56: 1217–1227.

Grosvenor W, Kaulin Y, Spielman AI et al. (2004) Biochemical enrichment and biophysical characterization of a taste receptor for l‐arginine from the catfish, Ictalurus puntatus. BMC Neuroscience 5: 25.

Hansen JL, Reed DR, Wright MJ et al. (2006) Heritability and genetic covariation of sensitivity to PROP, SOA, quinine HCl, and caffeine. Chemical Senses 31(5): 403–413.

Hayes JE, Sullivan BS and Duffy VB (2010) Explaining variability in sodium intake through oral sensory phenotype, salt sensation and liking. Physiology & Behaviour 100: 369–380.

Horio N, Yoshida R, Yasumatsu K et al. (2011) Sour taste responses in mice lacking PKD channels. PLoS ONE 6(5): e20007.

Huang AL, Chen X, Hoon MA et al. (2006) The cells and logic for mammalian sour taste detection. Nature 442(7105): 934–938.

Inoue M, Beauchamp GK and Bachmanov AA (2004a) Gustatory neural responses to umami taste stimuli in C57BL/6ByJ and 129P3/J mice. Chemical Senses 29(9): 789–795.

Inoue M, Glendinning JI, Theodorides ML et al. (2007) Allelic variation of the Tas1r3 taste receptor gene selectively affects taste responses to sweeteners: evidence from 129.B6‐Tas1r3 congenic mice. Physiological Genomics 32(1): 82–94.

Inoue M, Reed DR, Li X et al. (2004b) Allelic variation of the Tas1r3 taste receptor gene selectively affects behavioral and neural taste responses to sweeteners in the F2 hybrids between C57BL/6ByJ and 129P3/J mice. Journal of Neuroscience 24(9): 2296–2303.

Ishii A, Koide T, Takahashi A et al. (2011) B6‐MSM consomic mouse strains reveal multiple loci for genetic variation in sucrose octaacetate aversion. Behavioural Genetics 41(5): 716–723.

Keskitalo K, Knaapila A, Kallela M et al. (2007) Sweet taste preferences are partly genetically determined: identification of a trait locus on chromosome 16. American Journal of Clinical Nutrition 86(1): 55–63.

Kim UK and Drayna D (2005) Genetics of individual differences in bitter taste perception: lessons from the PTC gene. Clinical Genetics 67(4): 275–280.

Kim UK, Jorgenson E, Coon H et al. (2003) Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide. Science 299(5610): 1221–1225.

Li X, Bachmanov AA, Maehashi K et al. (2011) Sweet taste receptor gene variation and aspartame taste in primates and other species. Chemical Senses 36(5): 453–475.

Looy H and Weingarten HP (1991) Effects of metabolic state on sweet taste reactivity in humans depend on underlying hedonic response profile. Chemical Senses 16(2): 123–130.

Lugaz O, Pillias AM and Faurion A (2002) A new specific ageusia: some humans cannot taste l‐glutamate. Chemical Senses 27(2): 105–115.

Lush IE, Hornigold N, King P et al. (1995) The genetics of tasting in mice VII. Glycine revisited, and the chromosomal location of Sac and Soa. Genetics Research 66(2): 167–174.

Lyall V, Heck GL, Vinnikova AK et al. (2004) The mammalian amiloride‐insensitive non‐specific salt taste receptor is a vanilloid receptor‐1 variant. Journal of Physiology 558(part 1): 147–159.

Matsunami H, Montmayeur JP and Buck LB (2000) A family of candidate taste receptors in human and mouse. Nature 404(6778): 601–604.

Nelson TM, Lopezjimenez ND, Tessarollo L et al. (2010) Taste function in mice with a targeted mutation of the pkd1l3 gene. Chemical Senses 35(7): 565–577.

Nelson TM, Munger SD and Boughter JD Jr (2005) Haplotypes at the Tas2r locus on distal chromosome 6 vary with quinine taste sensitivity in inbred mice. BMC Genetics 6: 32.

Nie Y, Vigues S, Hobbs JR et al. (2005) Distinct contributions of T1R2 and T1R3 taste receptor subunits to the detection of sweet stimuli. Current Biology 15(21): 1948–1952.

Ninomiya Y, Kurenuma S, Nomura T et al. (1992) Taste synergism between monosodium glutamate and 5′‐ribonucleotide in mice. Comparative Biochemistry and Physiology A 101(1): 97–102.

Ninomiya Y, Sako N, Katsukawa H et al. (1991) Taste receptor mechanisms influenced by a gene on chromosome 4 in mice. In: Wysocki CJ and Kare MR (eds) Genetics of Perception and Communication, pp. 267–278. New York: Marcel Dekker.

Ossebaard CA, Polet IA and Smith DV (1997) Amiloride effects on taste quality: comparison of single and multiple response category procedures. Chemical Senses 22(3): 267–275.

Raliou M, Boucher Y, Wiencis A et al. (2009) Tas1R1–Tas1R3 taste receptor variants in human fungiform papillae. Neuroscience Letters 451(3): 217–221.

Reed DR, Li S, Li X et al. (2004) Polymorphisms in the taste receptor gene (Tas1r3) region are associated with saccharin preference in 30 mouse strains. Journal of Neuroscience 24(4): 938–946.

Shigemura N, Ohkuri T, Sadamitsu C et al. (2008) Amiloride‐sensitive NaCl taste responses are associated with genetic variation of ENaC α‐subunit in mice. American Journal of Physiology – Regulatory, Integrative and Comparative Physiology 294: R66–R75.

Shigemura N, Shirosaki S, Sanematsu K et al. (2009) Genetic and molecular basis of individual differences in human umami taste perception. PLoS ONE 4(8): e6717.

Soranzo N, Bufe B, Sabeti PC et al. (2005) Positive selection on a high‐sensitivity allele of the human bitter‐taste receptor TAS2R16. Current Biology 15(14): 1257–1265.

Whitney G and Harder DB (1986) Phenylthiocarbamide (PTC) preference among laboratory mice: understanding of a previously “unreplicated” report. Behavioral Genetics 16(6): 605–610.

Whitney G and Harder DB (1994) Genetics of bitter perception in mice. Physiology and Behaviour 56(6): 1141–1147.

Wise PM, Hansen JL, Reed DR et al. (2007) Twin study of the heritability of recognition thresholds for sour and salty taste. Chemical Senses 32(8): 749–754.

Wooding S, Kim UK, Bamshad MJ et al. (2004) Natural selection and molecular evolution in PTC, a bitter‐taste receptor gene. American Journal of Human Genetics 74(4): 637–646.

Yee KK, Sukumaran SK, Kotha R et al. (2011) Glucose transporters and ATP‐gated K+ (KATP) metabolic sensors are present in type 1 taste receptor 3 (T1r3)‐expressing taste cells. Proceedings of the National Academy of Sciences of the USA. 108(13): 5431–5436.

Zhao H, Yang JR, Xu H et al. (2010) Pseudogenization of the umami taste receptor gene Tas1r1 in the giant panda coincided with its dietary switch to bamboo. Molecular Biology and Evolution 27(12): 2669–2673.

Further Reading

Bachmanov AA (2008) Genetic architecture of sweet taste. In: Weerasinghe DK and DuBois GE (eds) Sweetness and Sweeteners: Biology, Chemistry and Psychophysics. ACS symposium series, 979. Oxford University Press.

Bachmanov AA (2010) Umami: fifth taste? Flavor enhancer? Perfumer and Flavorist 35(4): 52–57.

Bachmanov AA and Beauchamp GK (2007) Taste receptor genes. Annual Review of Nutrition 27: 389–414.

Bachmanov AA, Kiefer SW, Molina JC et al. (2003) Chemosensory factors influencing alcohol perception, preferences and consumption. Alcoholism: Clinical and Experimental Research 27(2): 220–231.

Basbaum AI, Kaneko A, Shepherd GM and Westheimer G (eds) (2008) The Senses: A Comprehensive Reference, vol. 4 (Firestein S and Beauchamp GK (eds)), Olfaction and Taste. San Diego: Elsevier/Academic Press.

Behrens M and Meyerhof W (2009) Mammalian bitter taste perception. Results & Problems in Cell Differentiation 47: 203–220.

Boughter JD and Bachmanov AA (2007) Behavioral genetics and taste. BMC Neuroscience 8(suppl. 3): S3.

Boughter JD Jr and Gilbertson TA (1999) From channels to behavior: an integrative model of NaCl taste. Neuron 22(2): 213–215.

Naim M, Nir S, Spielman AI et al. (2002) Hypothesis of receptor‐dependent and receptor‐independent mechanisms for bitter and sweet taste transduction: implications for slow taste onset and lingering aftertaste. In: Given P and Parades D (eds) Chemistry of Taste: Mechanisms, Behaviors, and Mimics. ACS Symposium Series; 825. Washington, DC: American Chemical Society.

Wysocki CJ and Kare MR (eds) (1991) Genetics of Perception and Communication. New York: Marcel Dekker.

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Bachmanov, Alexander A, and Boughter, John D(Jan 2012) Genetics of Taste Perception. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0023587]