Taste Receptor: Phenylthiocarbamide

Differences in the ability of humans to taste the sulfur-containing compound phenylthiocarbamide were first reported in the 1930s. PTC tasters find even low concentrations of the compound extremely bitter, while nontasters report little or no taste to the same concentration of PTC. The ability to taste PTC is inherited as a dominant trait. More precise analysis of the phenotype indicated that the "taster" gene is incompletely dominant to the "nontaster" gene, so that people with two copies of the taster gene have a lower threshold of sensitivity to PTC than people with only one copy. PTC is not a natural product, but similar sulfur-containing compounds are found in plants of the mustard family. Some of these compounds interfere with iodine metabolism, so the ability to taste them may confer some protection against thyroid disorders.

Although the trait has been a favorite standby for genetics classes for over 70 years, its chromosomal location and gene sequence were reported only in 2003 by Kim and others. The gene is one of many taste receptor proteins encoded by a large family of genes on the long arm of human chromosome 7 at positions q35-36. The taster condition is most strongly associated with the "PAV" haplotype, that is, the highest sensitivity to PTC is found in individuals with the amino acids Proline, Alanine and Valine at positions 49, 262 and 296 respectively in the protein. Most nontasters have the amino acids A, V and I at these three positions. The sequence reported by Kim is below. The protein appears to be a G-protein-coupled transmembrane protein. Seven helical regions wind back and forth through the membrane. These transmembrane regions are marked in the sequence below, as are the positions of the amino acids of the PAV haplotype.

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The PTC Taste Receptor Protein TAS2R38
Taster Variant


[ ] = Transmembrane regions
Enlarged font = PAV sites

MLTLTRIRTVSYEVRST
[FLFISVLEFAVGFLTNAFVFL]

VNFWDVVKRQPLSNSDC
[VLLCLSISRLFLHGLLFLSAI]
QLTHFQKLSEPLNHSYQA
[IIMLWMIANQANLWLAACLSL]
LYCSKLIRFSHTFLICLASWVSRKISQ
[MLLGIILCSCICTVLCVWCFF]

SRPHFTVTTVLFMNNNTRLNWQIKDLN
[LFYSFLFCYLWSVPPFLLFLV]

SSGMLTVSLGRHMRTMKVYTRNSRDPSLEAHIKALKSLVS
[FFCFFVISSC
AAFISVPLLIL]
WRDK
[IGVMVCVGIMAACPSGHAA
VL]
ISGNAKLRRAVMTILLWA
QSSLKVRADHKADSRTLC

LINK TO THE MUSIC

Notes on the Music:

The piece is introduced by the sequential entrance of the various voices used to represent various structural features of the protein. First high chimes play the DNA sequence in triplets. The voices representing the protein are partitioned into four sections. In the first, the five hydrophobic amino acids IVLFC are represented by piano. The midrange amino acids are played by harp representing the more nonpolar and guitar representing the more polar amino acids. A high chime then enters, playing the five charged amino acids HDEKR. Once these five voices are introduced, there is a pause during which only the DNA chimes play, and then the sequence of the protein is played from the beginning. Added to the voices already heard are two more, strings representing the seven transmembrane regions of the protein and three gong-like strokes that mark the positions of the PAV amino acids. The protein is played through only once, and the piece ends with the DNA repeating the final codon several times.

This piece was composed using ArtWonk algorithmic music software from Algorithmic Arts. It was revised 28 February 2004.

References:

Kim, U.; Jorgenson, E.; Coon, H.; Leppert, M.; Risch, N.; Drayna, D. Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide. Science 299: 1221-1225, 2003.

SwissProt Entry # P59533 (TR38, Human)