phenylthiocarbamide

The tested genetic taste phenomenon of PTC was discovered in 1931 when DuPont chemist Arthur Fox{{efn|name=Fox}} accidentally released a cloud of fine crystalline PTC. A nearby colleague complained about the bitter taste, while Fox, who was closer and should have received a strong dose, tasted nothing. Fox then continued to test the taste buds of assorted family and friends, setting the groundwork for future genetic studies. The genetic penetrance was so strong that it was used in paternity tests before the advent of DNA matching.{{cite web|author=Lee Phillips M|title=Scientists Find Bitter Taste Gene|url=http://faculty.washington.edu/chudler/bitter.html|date=15 July 2003|access-date=5 December 2009}}

The PTC taste test has been widely used in school and college practical teaching as an example of Mendelian polymorphism in human populations. Based on a taste test, usually of a piece of paper soaked in PTC (or the less toxic propylthiouracil (PROP)), students are divided into taster and non-taster groups. By assuming that PTC tasting is determined by a dominant allele at a single autosomal gene, and that the class is an unbiased sample from a population in Hardy–Weinberg equilibrium, students then estimate allele and genotype frequencies within the larger population. While this interpretation is broadly consistent with numerous studies of this trait, it is worth noting that other genes, sex, age and environmental factors influence sensitivity to PTC. Also, there are several alleles segregating at the major gene determining the taste of PTC, particularly in African populations, and the common "taster" allele is incompletely dominant (homozygotes for this allele are more sensitive to PTC than are heterozygotes). Additionally, PTC is toxic and sensitivity to the substitute, PROP, does not show a strong association with the gene controlling ability to taste PTC.

There is a large body of evidence linking the ability to taste thiourea compounds and dietary habits. Much of this work has focused on 6-propyl-2-thiouracil (PROP), a compound related to PTC that has lower toxicity. A supertaster has more of an ability to taste PTC. On the other hand, heavy cigarette smokers are more likely to have high PTC and PROP thresholds (i.e. are relatively insensitive).

In 1976, an inverse relationship between taster status for PTC and for a bitter component of the fruit of the tree Antidesma bunius was discovered.{{cite journal |author1=Henkin, R.I. |author2=W.T. Gillis |name-list-style=amp | year = 1977 | title = Divergent taste responsiveness to fruit of the tree Antidesma bunius | journal = Nature | volume = 265 | pages = 536–537 | doi = 10.1038/265536a0 | issue = 5594 | pmid = 834304| bibcode = 1977Natur.265..536H |s2cid=1259447 }} Research on the implications still continues.

Ability to taste PTC may be correlated with a dislike of plants in the genus Brassica, presumably due to chemical similarities. However, studies in Africa show a poor correlation between PTC tasting and dietary differences.

{{main|PTC tasting}}

Much of the variation in tasting of PTC is associated with polymorphism at the TAS2R38 taste receptor gene.{{cite journal|last1=Drayna|first1=Dennis|title=Human Taste Genetics|journal=Annual Review of Genomics and Human Genetics|date=2005|volume=6|pages=217–235|pmid=16124860|doi=10.1146/annurev.genom.6.080604.162340|url=https://zenodo.org/record/1234981|doi-access=free}} In humans, there are three SNPs (single nucleotide polymorphisms) along the gene that may render its proteins unresponsive.{{cite journal |vauthors=Kim UK, Jorgenson E, Coon H, Leppert M, Risch N, Drayna D | title=Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide |journal=Science |year=2003 | volume=299 | issue=5610 | pages=1221–1225 | pmid=12595690 | doi=10.1126/science.1080190 |bibcode=2003Sci...299.1221K| s2cid=30553230 }} There is conflicting evidence as to whether the inheritance of this trait is dominant or incompletely dominant. Any person with a single functional copy of this gene can make the protein and is sensitive to PTC.{{citation needed|date=April 2013}} Some studies have shown that homozygous tasters experience a more intense bitterness than people that are heterozygous; other studies have indicated that another gene may determine taste sensitivity.

The frequency of PTC taster and non-taster alleles vary in different human populations.{{cite journal |last1=Fareed |first1=M. |last2=Shah |first2=A. |last3=Hussain |first3=R. |last4=Afzal |first4=M. |year=2012 |title=Genetic study of phenylthiocarbamide (PTC) taste perception among six human populations of Jammu and Kashmir (India) |journal=Egypt J Med Hum Genet |volume=13 |pages=161–166 |doi=10.1016/j.ejmhg.2012.01.003 |issue=2|doi-access=free }} The widespread occurrence of non-taster alleles at intermediate frequencies, much more common than recessive alleles conferring genetic disease, across many isolated populations, suggests that this polymorphism may have been maintained through balancing selection.{{cite journal|last1=Campbell|title=Evolution of Functionally Diverse Alleles Associated with PTC Bitter Taste Sensitivity in Africa|journal=Molecular Biology and Evolution|date=2012|volume=29|issue=4|pages=1141–1153|pmc=3341826|display-authors=etal |pmid=22130969|doi=10.1093/molbev/msr293}}

Chimpanzees and orangutans also vary in their ability to taste PTC, with the proportions of tasters and non-tasters similar to that in humans.{{cite journal|last1=Fisher, Ford & Huxley|first1=R. A.|last2=Ford|first2=E. B.|last3=Huxley|first3=Julian|title=Taste-testing the Anthropoid Apes|journal=Nature|date=28 October 1939|volume=144|issue=750|pages=750|doi=10.1038/144750a0|bibcode=1939Natur.144..750F|hdl=2440/15129|s2cid=4136526|url=https://digital.library.adelaide.edu.au/dspace/bitstream/2440/15129/1/170.pdf|doi-access=free}} The ability to taste PTC is an ancestral trait of hominids that has been independently lost in humans and chimpanzees, through distinct mutations at TAS2R38.{{cite journal |last1=Wooding |first1=Stephen |title=Independent evolution of bitter-taste sensitivity in humans and chimpanzees |journal=Nature |date=2006 |volume=440 |issue=7086 |pages=930–934 |doi=10.1038/nature04655 |pmid=16612383 |display-authors=1 |last2=Grassi |first2=Christina |last3=Howard |first3=Michael T. |last4=Stone |first4=Anne C. |last5=Vazquez |first5=Maribel |last6=Dunn |first6=Diane M. |last7=Meyerhof |first7=Wolfgang |last8=Weiss |first8=Robert B. |last9=Bamshad |first9=Michael J. |bibcode=2006Natur.440..930W|s2cid=4395892 }}

{{notelist|notes=

{{efn

| name= Fox

| Arthur L. Fox commented in his 1932 paper: "Some time ago the author had occasion to prepare a quantity of phenyl thio carbamide, and while placing it in a bottle the dust flew around in the air. Another occupant of the laboratory, Dr. C. R. Noller, complained of the bitter taste of the dust, but the author, who was much closer, observed no taste and so stated. He even tasted some of the crystals and assured Dr. Noller they were tasteless but Dr. Noller was equally certain it was the dust he tasted. He tried some of the crystals and found them extremely bitter. With these two diverse observations as a starting point, a large number of people were investigated and it was established that this peculiarity was not connected with age, race or sex. Men, women, elderly persons, children, negroes, Chinese, Germans and Italians were all shown to have in their ranks both tasters and non-tasters."{{cite journal |last1=Fox |first1=Arthur L. |title=The Relationship between Chemical Constitution and Taste |journal=Proceedings of the National Academy of Sciences |date=January 1932 |volume=18 |issue=1 |pages=115–120 |doi=10.1073/pnas.18.1.115 |doi-access=free |pmid=16577421 |language=en |issn=0027-8424|pmc=1076170 }}{{pb}}Fox's finding received immediate attention, appearing in brief news stories in both Science and The Scientific News Letter. These stories focused on the curiosity of the finding, but they also caught the attention of geneticists, who were beginning to explore the organization of the human genome. Botanist Albert Francis Blakeslee replicated Fox's basic results and reported that PTC taste-blindness appears to be a recessive gene.{{cite journal |last=Wooding |first=Stephen |date= April 2006 |title=Phenylthiocarbamide: A 75-Year Adventure in Genetics and Natural Selection |journal=Genetics |volume=172 |issue=4 |pages=2015–2023 |publisher=National Center for Biotechnology Information, United States National Library of Medicine |doi=10.1093/genetics/172.4.2015 |pmid=16636110 |pmc=1456409 }}}}

}}

• TAS2R38
• PTC tasting
• List of Mendelian traits in humans
• Antidesma bunius
• Propylthiouracil
• Cilantro

{{Reflist|2}}

• [https://web.archive.org/web/20090324090838/https://www.nidcd.nih.gov/research/scientists/draynad.asp Dennis Drayna's home page.] Drayna has done extensive studies of PTC in various populations
• [https://web.archive.org/web/19961221210254/http://www.iit.edu/~smile/bi9113.html Population Study and Applications Using PTC Paper]
• [https://web.archive.org/web/20060215070738/http://genetics-education-partnership.mbt.washington.edu/cool/tools/ptcpaper.html Classroom activity description using PTC paper]
• {{OMIM|171200}} Thiourea tasting

{{Cruciferous Biochemistry}}

Category:Phenyl compounds

Category:Human genetics

Category:Thioureas

Category:Bitter compounds