PTC Background Information

Here is an excellent lecture on PTC tasting genetics that is part of the Holiday Lecture Series at HHMI.

What foods an organism finds palatable is an important factor in what the organism will eat. Humans regularly make both good and bad dietary choices based on primarily on taste. We have expected for some time that some component of taste is genetically controlled, but in recent years scientists have discovered that there are many more tasting genes then we originally thought.

Bitter tasting is the most well studied taste perception. In humans, the ability to taste bitter compounds is known to involve at least 25 different genes for bitter receptors (Drayna, 2005 [3]). All these genes have a single exon that encodes a transmembrane protein. Of the bitter tasting genes, the best understood is the gene for tasting PTC.

For tasters, PTC has an extremely nasty flavour, while in nontasters, the chemical has little or no flavour at all. While PTC is not a chemical that humans would normally eat, it mimics the taste of bitter compounds that are naturally found in both edible and poisonous substances. In particular, PTC mimics the taste of many poisonous plant compounds as well as bitter tasting substances found in cruciferous vegetables (e.g. cabbage and broccoli).

The heritability of PTC tasting ability was first identified in 1932 (Blakeslee, 1932 [1]; Fox, 1932 [5]) and, until recently, the ability to taste PTC was thought to be inherited as a simple, dominant Mendelian trait (Fox, 1932 [5]). For decades people were classified as either “tasters” or “nontasters”, even as evidence for a more continuous distribution in tasting ability accumulated. The riddle of PTC tasting was partially solved when the gene responsible was identified (Kim et al., 2003 [6]).

The PTC gene (TASR38) has several variable nucleotide positions (such variations are referred to as Single Nucleotide Polymorphisms or SNPs) (Kim et al., 2003 [6], Wooding et al., 2004 [7]) but only three positions account for the majority of observed SNPs. These positions are nucleotides 145, 785 and 886 (Table 1). Since most PTC haplotypes vary at at least one of these three positions, they are named for the variant amino acids they encode (Table 2).

Table 1. SNP variation in the PTC (TAS2R38) gene. Shading indicates the most common variant positions. Adapted from Drayna, 2005 [3].
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Table 2. PTC haplotypes identified in 165 humans (330 haplotypes). Only the amino acid sequence found at the three most common SNPs are indicated (Wooding et al., 2004 [7]). Sample sizes, African 31, Asian 69, European 55, Indigenous North American 20.
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The ability to taste PTC is most frequently associated with the (usually) dominant haplotype, PAV (Kim et al., 2003 [6]) (Table 3). The inability to taste PTC is most frequently associated with the (usually) recessive haplotype, AVI. These two haplotypes are found most frequently in human populations (greater than 90% of haplotypes are AVI or PAV) (Kim et al., 2003 [6]Wooding et al., 2004 [7]). The other haplotypes (AAI, AAV, PVI) are associated with intermediate tasting ability (Buff et al. 2005 [2}.

Theoretically, the known SNPs could combine to form dozens of distinct haplotypes, but so far only a few haplotypes have been observed (Wooding et al., 2004 [7]). The three most common SNPs could combine to form 8 distinct haplotypes, but only 5 haplotypes have been observed (and 2 of the 5 account for less than 3% of observed haplotypes) (Table 1).

PTC alleles are named for the variant amino acids they encode (Table 2). The ability to taste PTC is most frequently associated with a dominant allele termed PAV (Kim et al., 2003 [6]) (Table 3). This is also the most common allele found in human populations (Wooding et al., 2004 [7]).

Table 3. Haplotype combinations associated with taste phenotypes (Kim et al., 2003).
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Like all other bitter receptors, PTC is a transmembrane G-coupled protein (Floriano et al., 2006 [4]). It appears that all variant PTC alleles encode proteins that have a structure similar to the PAV protein, even though they have lost some or all of their function in PTC tasting. For example, the AVI variant appears capable of inserting into the membrane and recognizing the PTC ligand. The loss of tasting ability seems to be due to the loss of signal transduction in the cell (signal transduction refers to molecular signals within a cell that result in some cellular change) (Floriano et al., 2006 [4]). The fact that all non-taster alleles still encode full-length protein is quite different from what we usually see in recessive alleles at other loci. It is much more common to see a recessive allele encoding no protein, or a much altered version of the wild-type protein.

Citations
1. Blakeslee, A.F. (1932). Genetics of sensory thresholds: taste for phenyl thio carbamide. Proc Natl Acad Sci USA 18, 120.
2. Bufe, B., Breslin, P., Kuhn, C., Reed, D., Tharp, C., Slack, J., Kim, U., Drayna, D. and Meyerh, W. (2005) The Molecular Basis of Individual Differences in Phenylthiocarbamide and Propylthiouracil Bitterness Perception. Current Biology, Vol. 15, 322–327
3. Drayna, D. (2005). HUMAN TASTE GENETICS. Annu. Rev. Genom. Human Genet. 6, 217–235.
4. Floriano, W.B., Hall, S., Vaidehi, N., Kim, U., Drayna, D., and Goddard, W.A., III (2006). Modeling the human PTC bitter-taste receptor interactions with bitter tastants. J Mol Model 12, 931–941.
5. Fox, A.L. (1932). The relationship between chemical constitution and taste. Proc Natl Acad Sci USA 18, 115.
6. Kim, U., Jorgenson, E., Coon, H., Leppert, M., Risch, N., and Drayna, D. (2003). Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide. Science 299, 1221.
7. Wooding, S., Kim, U.-K., Bamshad, M.J., Larsen, J., Jorde, L.B., and Drayna, D. (2004). Natural selection and molecular evolution in PTC, a bitter-taste receptor gene. Am. J. Hum. Genet. 74, 637–646.
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