![Phenylthiocarbamide structure](https://upload.wikimedia.org/wikipedia/commons/8/89/Phenylthiocarbamide_structure.svg)
PTC tasting is a classic
genetic marker A genetic marker is a gene or DNA sequence with a known location on a chromosome that can be used to identify individuals or species. It can be described as a variation (which may arise due to mutation or alteration in the genomic loci) that can be ...
in
human population genetics
Humans (''Homo sapiens'') are the most abundant and widespread species of primate, characterized by bipedalism and exceptional cognitive skills due to a large and complex brain. This has enabled the development of advanced tools, culture, ...
investigations.
History
In 1931 Arthur Fox, a chemist at DuPont, in Wilmington, Delaware, synthesized phenylthiocarbamide (PTC). Some researchers reported a bitter taste when entering his laboratory, while others, including Fox himself, experienced no such sensation. Further study of this phenomenon by L.H. Snyder in 1931 led to the conclusion that the inability to taste PTC is a recessive trait.
In 1932, Albert Blakeslee conducted a large-scale study involving the inheritance of PTC tasting within families that concluded that PTC tasting sensitivity is very likely a complex Mendelian trait whose variance is overwhelmingly dependent on a single gene locus; however, it is likely that a few other genes have a smaller effect as well.
In 1939 Fisher et al. found that the genetic frequency of PTC tasting was the same in chimps and humans. This similarity suggests that whatever gene controls for PTC tasting must have some sort of a selective advantage in order to have either evolved and been maintained for millions of years since before humans and chimps diverged into separate species, or to have evolved in two separate events after species divergence. Since finding out that PTC tasting had an apparent naturally selective advantage, scientists began to hypothesize that this advantage was that the ability to taste natural chemicals similar to PTC helped human ancestors stay away from some toxic plants. Substances that resemble PTC today are in some vegetables from the cabbage family (''Brassicaceae''), such as broccoli and Brussels sprouts.
In 1950, William Boyd found evidence that the same gene that controls for PTC tasting also controls for the "tasting" of a different compound that acts as an antithyroid drug similar to that found in cabbage plants. Despite all of this compelling evidence for PTC "tasters" to have a selective advantage over "non-tasters," there was no explanation for the consistent proportions of "non-taster" in human and chimp populations until scientists discovered that subjects with a "PTC non-taster" phenotype were able to taste a different bitter compound that "PTC tasters" could not. This compound was juice from an
antidesma
''Antidesma'' is a genus of tropical plant in the family Phyllanthaceae formally described by Linnaeus in 1753.
It is native to tropical Africa, S + E + SE Asia, Australia, and various oceanic islands. The greatest diversity occurs in Southe ...
plant and notably, this study found a perfectly inverse relationship between PTC and antidesma tasting. These results were replicated in 2005 by another team of researchers who found the same inverse relationship between PTC and antidesma tasting However, in 2018, Davide Risso and colleagues expanded upon this relationship when they discovered a notable difference from previous studies. What they found was that there appeared to be a small population of people who could taste both "PTC" and antidesma as bitter. This finding could suggest a possible advantage for heterozygotes given their ability to taste both bitter compounds.
Genetics
In 1999, Mark Hoon and a team of researchers discovered a gene family that codes for taste receptors, specifically for the "bitter" flavor which they called the TAS2R gene family. The locus of the gene (or genes) that control for PTC tasting is hypothesized to be a part of this TAS2R gene family. In 2003,
Dennis Drayna
Dennis T. Drayna (born 1952) is an American human geneticist known for his contributions to stuttering, human haemochromatosis, pitch, and taste. He is currently the Section Chief of Genetics of Communication Disorders at the U.S. National Inst ...
and his colleagues at the
National Institutes of Health
The National Institutes of Health, commonly referred to as NIH (with each letter pronounced individually), is the primary agency of the United States government responsible for biomedical and public health research. It was founded in the late ...
(NIH), as well as a team of researchers led by Un-kyung Kim,
discovered that a variation at the
TAS2R38
Taste receptor 2 member 38 is a protein that in humans is encoded by the ''TAS2R38'' gene. TAS2R38 is a bitter taste receptor; varying genotypes of ''TAS2R38'' influence the ability to taste both 6-''n''-propylthiouracil (PROP) and phenylthiocar ...
gene locus is responsible for an overwhelming majority of the variance in PTC tasting sensitivity (50-80%).
It has been suggested that taste and smell receptors are controlled by
TAS2R38
Taste receptor 2 member 38 is a protein that in humans is encoded by the ''TAS2R38'' gene. TAS2R38 is a bitter taste receptor; varying genotypes of ''TAS2R38'' influence the ability to taste both 6-''n''-propylthiouracil (PROP) and phenylthiocar ...
, with a small intron gene of about 1000 nucleotides. It is a member of the family of G protein-coupled or 7 trans membrane cross
receptors
Receptor may refer to:
*Sensory receptor, in physiology, any structure which, on receiving environmental stimuli, produces an informative nerve impulse
*Receptor (biochemistry), in biochemistry, a protein molecule that receives and responds to a n ...
. The binding of a ligand to the extracellular region of the receptor sets an action potential that sends an impulse to the sensory cortex of the brain, where it is interpreted as a bitter taste.
This allows an experimental test for
SNP at position 145 that has the highest correlation to the sample 3 polymorphisms. The test isolates DNA from cheek cells by a simple salt mouthwash and amplification of a region of the gene
TAS2R38
Taste receptor 2 member 38 is a protein that in humans is encoded by the ''TAS2R38'' gene. TAS2R38 is a bitter taste receptor; varying genotypes of ''TAS2R38'' influence the ability to taste both 6-''n''-propylthiouracil (PROP) and phenylthiocar ...
. The amplified fragment (amplicon) is incubated with the restriction enzyme
HaeIII
''Hae''III is one of many restriction enzymes ( endonucleases) a type of prokaryotic DNA that protects organisms from unknown, foreign DNA. It is a restriction enzyme used in molecular biology laboratories. It was the third endonuclease to be is ...
, comprising the SNP in their recognition sequence GGCC. HaeIII cuts the taster allele (having the sequence GGCC); this generates a length
polymorphism, and the 2 alleles can be easily separated in an agarose gel.
Virtually all non-tasters (dd) cannot taste PTC, while homozygous tasters (''TT'') occasionally report an inability or weak ability to taste the chemical. The heterozygous
genotype
The genotype of an organism is its complete set of genetic material. Genotype can also be used to refer to the alleles or variants an individual carries in a particular gene or genetic location. The number of alleles an individual can have in a ...
(''Tt'') has the "leakiest"
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
as reduced or absent tasting ability is relatively common. This is formally called a ''heterozygous effect''.
Harris – Kalmus' threshold solutions and differentiation
In 1949, Harris and Kalmus developed a method for differentiation of bimodal threshold stimuli for tasting
PTC. They proposed a series of 13 solutions of these substances with serial water by halves from the initial concentration of 0.13%, so that the solution in the final test contained only a few molecules of this substance. Pure water was used as the fourteenth test liquid to provide a control. Differentiation between the two
phenotype
In genetics, the phenotype () is the set of observable characteristics or traits of an organism. The term covers the organism's morphology or physical form and structure, its developmental processes, its biochemical and physiological proper ...
s of "tasters" and "non-tasters" occurred with the fifth solution. Then assuming that the conditional
dimorphism controlled by two
allele
An allele (, ; ; modern formation from Greek ἄλλος ''állos'', "other") is a variation of the same sequence of nucleotides at the same place on a long DNA molecule, as described in leading textbooks on genetics and evolution.
::"The chro ...
of the corresponding
gene
In biology, the word gene (from , ; "...Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' or ''birth'' or ''gender'') can have several different meanings. The Mendelian gene is a ba ...
locus, the allele which controls the absence of sensitivity to taste PTC is
recessive
In genetics, dominance is the phenomenon of one variant (allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant and t ...
homozygote
Zygosity (the noun, zygote, is from the Greek "yoked," from "yoke") () is the degree to which both copies of a chromosome or gene have the same genetic sequence. In other words, it is the degree of similarity of the alleles in an organism.
Mo ...
.
*Testing solutions scale after Harris and Kalmus
Although the view of the genetics of individual sensitivity to taste PTC changed, practically all the current data on the PTC taste (in)ability established certain of these substances originate from research by Harris and Kalmus, and such investigations are still taken. This is probably because it is not suggested a better method for mass
population genetics
Population genetics is a subfield of genetics that deals with genetic differences within and between populations, and is a part of evolutionary biology. Studies in this branch of biology examine such phenomena as adaptation, speciation, and pop ...
projects.
Non-taster phenotype distribution in selected populations
References
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Urea cycle
Sensors
Classical genetics