PTC – Cell Signaling, genetics, and Evolution

PTC = phenylthiocarbamide What do you notice about the structure of PTC?   It is not found in nature, but chemically similar structures (glucosinolates) are found in bitter foods

How Do you sense taste? On your table diagram how you differentiate tastes. In other words? How do you know if you taste PTC? (Think cell signaling here!)

Cell Signaling PathwayS!!!

T = tasting t = non-tasting PTC Tasting Most biology courses (high school/introductory college) claim Mendelian Genetics The graphic on the right is from the University of Utah (https://learn.genetics.utah.edu/content/basics/ptc/_) We will start with this assumption However: 85% of tasting PTC is due to the PAV/AVI haplotype (we will come back to what this means!) T = tasting  t = non-tasting 

T =Tasters t = Non-taster Can you taste PTC? Tasters Non-taster - Record your results on the board - calculate the frequencies   T =Tasters t = Non-taster   Allelic Frequencies p q Genotypic Frequencies p2 2pq q2 Tasters Non-taster Whole population  

Explain the Figure! This figure shows that the ability to taste phenylthiocarbamide (PTC) varies significantly from one population to another worldwide. The data plotted in the figure were extracted from a review article (Guo & Reed, 2001) that summarizes findings from tests conducted in more than 370 population samples worldwide, all published between 1934 and 1998. https://www.nidcd.nih.gov/health/statistics/global-variation-sensitivity-bitter-tasting-substances-ptc-or-prop

Explain the figure Frequency of PTC “nontaster” allele, estimated from 348 populations described by Guo and Reed (2001) under the assumption that the inability to taste PTC is attributable to the recessive allele in a one-locus, two- allele system.

Compare and Contrast This figure shows that the ability to taste phenylthiocarbamide (PTC) varies significantly from one population to another worldwide. The data plotted in the figure were extracted from a review article (Guo & Reed, 2001) that summarizes findings from tests conducted in more than 370 population samples worldwide, all published between 1934 and 1998. Frequency of PTC “nontaster” allele, estimated from 348 populations described by Guo and Reed (2001) under the assumption that the inability to taste PTC is attributable to the recessive allele in a one-locus, two-allele system.

Why is there variation in Allelic and phenotypic frequency for PTC Tasting? Diet Detecting poison/dangerous chemicals (avoid poisonous plants)  TAS2R38 non-taster haplotype has an unknown function (detect an unknown toxin TAS2R38 linked to ability of upper respiratory cells to clear bacteria Loss of function – what if there was no selective pressure and random mutations built up (https://www.nature.com/articles/486S16a.pdf) Thyroid – naturally occurring  chemicals similar to PTC inactivate thyroid function Not natural selection at all - Genetic Drift

Modeling GENETIC DRIFT – Changes in a gene pool (Allele Frequencies due to chance)

Modeling a BOTTLENECK Or founder Effect  calculate the allelic and genotypic frequencies   T =Tasters t = Non-taster   Allelic Frequencies p q Genotypic Frequencies p2 2pq q2 Tasters Non-taster Whole population  

Modeling a BottleNeck or Founder Effect calculate the new allelic and genotypic frequencies   T =Tasters t = Non-taster   Allelic Frequencies  p q Genotypic Frequencies p2 2pq q2   Tasters Nontaster Whole population

PTC Tasting 85% of tasting PTC is due to the PAV/AVI haplotype – It isn’t as simple as: T = tasting  T = non-tasting  (There are other haplotypes that aren’t as common.  Other factors such as dry mouth, other chemicals in foods, age, nutrient deficiency (zinc), illness, etc. can impact if you can taste PTC) 

TAS2R38 – taste 2 receptor member 38 Chromosome 7 Codes for a g-protein coupled receptor "There are three amino acid polymorphisms: alanine/proline (A/P) at amino acid position 49, valine/alanine (V/A) at position 262, and isoleucine/valine (I/V) at position 296. The three polymorphisms have 8 possible combinations (haplotypes), but two make up more than 95 percent of all haplotypes in European and Asian populations: AVI and PAV, named after the amino acids at positions 49, 262 and 296. AVI/AVI homozygotes are mostly non-tasters, while AVI/PAV heterozygotes and PAV/PAV homozygotes are mostly tasters."

What the heck does that mean? The difference between tasters and non-tasters are at amino acids (single nucleotide polymorphisms(SNPs) #49 alanine/proline (A/P) #262 valine/alanine (V/A)  #296 isoleucine/valine (I/V) There are 8 combinations of these three amino acid differences AVI and PAV make up more than 95 percent of all haplotypes in European and Asian populations AAV haplotypes was present at a frequency of 3 percent in Europe, while AAV, AAI and PVI were found only in sub- Saharan African populations AVI = Non-taster (t) PAV = Taster (T) Figure 8. Predicted binding sites of agonists in bitter taste receptors:

Sources and Images https://learn.genetics.utah.edu/content/basics/ptc/_) https://www.nidcd.nih.gov/health/statistics/global-variation-sensitivity-bitter-tasting-substances-ptc-or-prop https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1181941/ https://ghr.nlm.nih.gov/gene/TAS2R38#resources https://www.ncbi.nlm.nih.gov/gene/5726 https://www.nature.com/articles/486S16a.pdf https://www.semanticscholar.org/paper/3D-Structure-Prediction-of-TAS2R38-Bitter-Receptors-Tan- Abrol/b9b653fa4124cd21a304da0f6da4629eac079566/figure/8 https://www.ncbi.nlm.nih.gov/books/NBK11148/ https://besjournals.onlinelibrary.wiley.com/doi/full/10.1111/j.1365-2435.2008.01523.x https://www.hsph.harvard.edu/nutritionsource/2016/05/31/super-tasters-non-tasters-is-it-better-to-be-average/ http://udel.edu/~mcdonald/mythptc.html https://www.nature.com/articles/srep25506

Fun facts! - Herbivores have evolved physiological and behavioral mechanisms for processing plant toxins (smell, intestinal receptors, enzymes, etc)  https://besjournals.onlinelibrary.wiley.com/doi/full/10.1111/j.1365 -2435.2008.01523.x