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2. Cokl, A., and Millar, J.G. (2009). Manipulation 7. Vosshall, L.B. (2008). Scent of a fly. Neuron 59, cuticular hydrocarbons using matrix-assisted of signaling for monitoring and control of 685–689. laser desorption/ionization mass spectrometry. insect pests. In Biorational Control of 8. Ferveur, J.F. (2005). Cuticular hydrocarbons: J. Chem. Ecol. 32, 409–434. Arthropod Pests. I. Isaaya and R.A. Horowitz, their evolution and roles in Drosophila eds. (Berlin, New York: Springer). pheromonal communication. Behav. Genet. 1 3. Wilson, E.O. (1970). Chemical communication 35, 279–295. Department of Biology, University of within animal species. In Chemical Ecology, 9. Mpuru, S., Blomquist, G.J., Schal, C., Roux, M., Toronto Mississauga, 3359 Mississauga E. Sondheimer and J.B. Simeone, eds. (New Kuenzli, M., Dusticier, G., Cle´ ment, J.-L., and Road North, Mississauga, ON L5L 1C6, York: Academic Press), pp. 133–155. Bagneres, A.-G. (2001). Effect of age and Canada. 2Department of Entomology, 4. Millar, J.G. (2000). Polyene hydrocarbons and sex on the production of internal and external epoxides: a second major class of lepidopteran hydrocarbons and pheromones in the housefly, University of California Riverside, sex attractant pheromones. Annu. Rev Musca domestica. Insect Biochem. Mol. Biol. 3401 Watkins Drive, Riverside, Entomol. 45, 575–604. 31, 139–155. CA 92521, USA. 5. Jallon, J.M. (1984). A few chemical words 10. Yew, J.Y., Cody, R.B., and Kravitz, E.A. (2008). E-mail: [email protected], exchanged by Drosophila during courtship Cuticular hydrocarbon analysis in the awake [email protected] and mating. Behav. Genet. 14, 441–478. behaving fly using direct analysis in real-time 6. Wyatt, T.D. (2003). Pheromones and Animal time-of-flight mass spectrometry. Proc. Natl. Behavior: Communication by Smell and Acad. Sci. USA 105, 7135–7140. Taste (Cambridge, UK: Cambridge University 11. Cvacka, J., Jiros, P., Sobotnik, J., Hanus, R., Press). and Svatos, A. (2006). Analysis of insect DOI: 10.1016/j.cub.2009.06.051

Taste Perception: How Sweet It Is Fushan et al. [9] measured the ability of 144 individuals to detect various (To Be Transcribed by You) concentrations of sugar solutions and searched for polymorphisms in the TAS1R2 and TAS1R3 genes in these In mammals, sweet taste is mediated largely by a single receptor. New work individuals that correlate with shows that polymorphisms in the promoter region of one subunit contribute to perception. They found several variation in sweet perception in the human population. variations that change amino-acid sequences in both the TAS1R2 and Joel D. Mainland We have known for some time that the TAS1R3 subunits of the receptor. and Hiroaki Matsunami taste world of one individual is different Surprisingly, however, variations in the from that of another — humans’ two subunits did not correlate with a Sweet taste perception is the source of sensitivity to sweet and bitter both great pleasure and terrible public compounds can show dramatic health problems: triple chocolate variation — but the basis for this blackout cake and tooth decay; Meyer variability has been elusive. As lemon ice cream profiteroles and information from the human genome obesity; passion fruit pavlova with became available, the field of lemon verbena cream and diabetes. chemoreception found a number of Humans were experimenting with cases where receptor genes show methods for altering our sweet taste polymorphisms among individuals. perception long before we knew the In some cases, researchers showed identity of the sweet receptor, whether that these variations in the primary we were chewing on miracle fruit to receptor alter perception of the sensory make sour foods taste sweet or world. For example, previous work drinking gymnema sylvestre tea to on bitter receptors in vitro showed make sugar taste like sand [1]. Earlier that three one-letter changes in the this decade, several groups [2–8] hTAS2R38 receptor lead to much higher showed that in mammals, sweet taste sensitivity to certain bitter compounds is mediated largely by a single known as glucosinolates [10]. receptor composed of the two Consequently, humans with this variant subunits TAS1R2 and TAS1R3 receptor are more sensitive to (Figure 1A). Understanding how glucosinolates [11,12]. While humans this receptor responds to sugars may have over 20 receptors for bitter tastes, lead to the development of new they have only one for sweet taste, sweeteners and inhibitors that making it an attractive place to look for would be useful to both the food genetic changes that lead to variation in Figure 1. Sweet receptor polymorphism. industry and medicine. In this issue sweet perception. Indeed, variations in (A) The mammalian sweet receptor is made of Current Biology, Fushan et al. [9] the sweet receptor across species have up of two subunits, TAS1R2 and TAS1R3. examine how polymorphisms in already been shown to have effects on (B) Two one-letter changes in the promoter this receptor, the point of sweet perception — domestic house region, from C-C to T-T, reduce transcription of the TAS1R3 subunit. Humans with the T-T convergence for both dessert and cats have a defect in the TAS1R2 gene allele have a reduced taste sensitivity to disease, alter our perception of and are therefore indifferent to the taste sucrose relative to humans with the C-C sucrose. of sucrose [13]. allele. Figures drawn by Senmiao Zhan. Current Biology Vol 19 No 15 R656 shift in the subjects’ sweet perception. sensitivity to sucrose, are most 5. Damak, S., Rong, M., Yasumatsu, K., Kokrashvili, Z., Varadarajan, V., Zou, S., The authors confirmed in vitro that, common in sub-Saharan Africa, while Jiang, P., Ninomiya, Y., and Margolskee, R.F. despite all of these variations, the the C allele is the major variant in all (2003). Detection of sweet and umami taste in function of these receptors, namely geographic regions except Africa. the absence of taste receptor T1r3. Science 301, 850–853. activation by sweet compounds, was Fushan et al. [9] hypothesize that 6. Kitagawa, M., Kusakabe, Y., Miura, H., largely unaffected. What, then, was in tropical climates, where sugar Ninomiya, Y., and Hino, A. (2001). Molecular genetic identification of a candidate receptor causing some people to be more sources are plentiful, the ability to gene for sweet taste. Biochem. Biophys. Res. sensitive to sweet compounds? The taste a small amount of sugar was Commun. 283, 236–242. answer was not in the receptor less important than in cold climates, 7. Max, M., Shanker, Y.G., Huang, L., Rong, M., Liu, Z., Campagne, F., Weinstein, H., sequence, but in an upstream flanking where sugar sources are scarce. Damak, S., and Margolskee, R.F. (2001). region of DNA. People with two Interestingly, the subunit affected Tas1r3, encoding a new candidate taste receptor, is allelic to the sweet one-letter changes in the promoter by this promoter variation, TAS1R3, responsiveness locus Sac. Nat. Genet. sequence of the TAS1R3 gene have plays a dual role, partnering with a third 28, 58–63. a decreased sensitivity to sucrose subunit to form the umami receptor 8. Zhao, G.Q., Zhang, Y., Hoon, M.A., Chandrashekar, J., Erlenbach, I., Ryba, N.J., (Figure 1B). (umami translates from Japanese as and Zuker, C.S. (2003). The receptors for The promoter sequence interacts ‘delicious’ but in this context is perhaps mammalian sweet and umami taste. Cell 115, 255–266. with transcription factors to regulate closer to ‘savory’). TAS1R2, in contrast, 9. Fushan, A.A., Simons, C.T., Slack, J.P., the amount of receptor transcripts. is believed to only form a sweet Manichaikul, A., and Drayna, D. (2009). Fushan et al. [9] verified in vitro that receptor complex. This raises the Allelic polymorphism within the TAS1R3 promoter is associated with human taste the promoter variant resulting in lower possibility that the same changes sensitivity to sucrose. Curr. Biol. 19, amounts of the TAS1R3 transcript that affect sweet taste may also 1288–1293. 10. Bufe, B., Breslin, P.A., Kuhn, C., Reed, D.R., correlated with reduced sensitivity to affect the perception of umami-tasting Tharp, C.D., Slack, J.P., Kim, U.K., Drayna, D., sucrose. This strengthened the case amino acids such as monosodium and Meyerhof, W. (2005). The molecular that polymorphisms in the promoter glutamate. basis of individual differences in phenylthiocarbamide and propylthiouracil region cause changes in sweet taste This new evidence that sweet taste bitterness perception. Curr. Biol. 15, perception. Some caution is warranted perception may be under partial 322–327. 11. Sandell, M.A., and Breslin, P.A. (2006). here, however, as in vitro studies of genetic control [9] is exciting because it Variability in a taste-receptor gene determines taste receptors are not carried out in may allow for more personalized health whether we taste toxins in food. Curr. Biol. 16, taste cells, as there are no available interventions. Those interventions in R792–R794. 12. Kim, U.K., Jorgenson, E., Coon, H., Leppert, M., taste-cell derived cell lines available. turn will hopefully ensure that you Risch, N., and Drayna, D. (2003). Positional Instead, the in vitro work is performed spend less time in the dentist’s chair cloning of the human quantitative trait locus underlying taste sensitivity to in cells derived from the bile duct, and more time enjoying your brandied phenylthiocarbamide. Science 299, which endogenously express TAS1R3. cherry truffle torte. 1221–1225. It is possible that the proteins 13. Li, X., Li, W., Wang, H., Cao, J., Maehashi, K., Huang, L., Bachmanov, A.A., Reed, D.R., interacting with this promoter region References Legrand-Defretin, V., Beauchamp, G.K., et al. 1. Bartoshuk, L.M. (1974). Taste illusions: some (2005). Pseudogenization of a sweet-receptor could be quite different in taste cells, demonstrations. Ann. NY Acad. Sci. 237, gene accounts for cats’ indifference toward 279–285. thus causing different effects in sugar. PLoS Genet. 1, 27–35. 2. Bachmanov, A.A., Li, X., Reed, D.R., mediating TAS1R3 transcript levels. 14. Kim, U.K., Wooding, S., Riaz, N., Jorde, L.B., Ohmen, J.D., Li, S., Chen, Z., Tordoff, M.G., and Drayna, D. (2006). Variation in the human An evolutionary analysis indicated de Jong, P.J., Wu, C., West, D.B., et al. (2001). TAS1R taste receptor genes. Chem. Senses 31, Positional cloning of the mouse saccharin that the variations are not just the result 599–611. preference (Sac) locus. Chem. Senses 26, of neutral genetic drift, suggesting 925–933. they may have a role in the receptor’s 3. Nelson, G., Hoon, M.A., Chandrashekar, J., Department of Molecular Genetics and function [14]. What might be the Zhang, Y., Ryba, N.J., and Zuker, C.S. (2001). Microbiology, Duke University Medical Mammalian sweet taste receptors. Cell 106, selective advantage of a change in 381–390. Center, Durham, NC 27710, USA. sweet perception? Here, the ethnic 4. Montmayeur, J.P., Liberles, S.D., E-mail: [email protected] Matsunami, H., and Buck, L.B. (2001). A variation may hold some clue. The candidate taste receptor gene near a sweet T alleles, associated with a decreased taste locus. Nat. Neurosci. 4, 492–498. DOI: 10.1016/j.cub.2009.06.050