An example from Lauri's 205 lab manual
Purpose of what I was writing
To give background information for a biology 205 lab in which the students will look at the relationship between what PTC alleles a person has and what their tasting ability is. Student's will be sequencing the PTC gene and determining the haplotypes of several individuals (tasting ability of each person will be known as well).
In this particular introductory paragraph I wanted to summarize the following
We have known that PTC tasting/nontasting is genetically determined for a long time.
Recently the gene has been identified and cloned, making it possible to investigate at a molecular level, why some people can taste PTC and some can't.
Summarize what we know so far about the relationship between sequence variations and tasting ability.
Here are the associated references & my brief summary of what the articles say.
Blakeslee AF. 1932. Genetics of sensory thresholds: taste for phenyl thio carbamide. Proc Natl Acad Sci USA 18:120.
Fox AL. 1932. The relationship between chemical constitution and taste. Proc Natl Acad Sci USA 18:115.
- Original description of the ability of some people to taste PTC while others cannot.
- Investigated the tastes of structurally similar molecules to narrow done what the tasters must be tasting.
- Fox identified all sorts of similar compounds that were bitter tasting to both tasters and non-tasters, as well as several compounds that had no taste and completely different tastes (such as sweet tasting).
- Fox suggested that the solubility of PTC in the saliva might vary between tasters and non-tasters (no evidence of this was found).
Kim U, Jorgenson E, Coon H, Leppert M, Risch N, Drayna D. 2003. Positional cloning of the human quantitative trait locus underlying taste sensitivity to phenylthiocarbamide. Science 299:1221.
- Actual cloning of the PTC gene (by linkage analysis using Utah center families).
- Found 3 SNPs and 5 haplotypes associated with this gene (264 samples).
- AVI (47%) and PAV (49%) are most common haplotypes (96% of the haplotypes in this sample) - note that actual sample ancestry was not fully disclosed but appears to be primarily European (Utah sample of 180 is all European), NIH sample (29 Caucasians, 16 East Asians).
- Found PAV associated in a dominant fashion with tasting, AVI with the recessive nontasting. The minor haplotypes AAV, AAI and PVI did not appear to be associated with tasting.
- Looked at several nonhuman primates and found all were homozygous for PAV (sample size unknown).
Wooding S, Kim U-K, Bamshad MJ, Larsen J, Jorde LB, Drayna D. 2004. Natural selection and molecular evolution in PTC, a bitter-taste receptor gene. Am. J. Hum. Genet. 74:637–646.
- Sequenced PTC gene from 330 chromosome samples (African, Asian, European and North American and found 5 SNPs and 7 haplotypes (actually number of possible haplotypes is 2 to the 5th or 32.
- Used statistical analysis to investigate the role of natural selection in maintaining both taster and nontaster alleles in human populations.
- "the hsA and hsG haplotypes were both found at intermediate frequencies: 0.55 and 0.38. A variety of factors, including population subdivision and balancing natural selection, can lead to the presence of two or more intermediate-frequency haplotypes in gene genealogies (Marjoram and Donnelly 1994; Bamshad and Wooding 2003). The evolution of two or more intermediate-frequency clusters is also surprisingly common under selectively neutral conditions (Slatkin and Hudson 1991)." — direct quote from the paper
- Using statistical methods (ME - that I don't understand), these authors concluded that balancing natural selection is responsible for maintaining the 2 major haplotypes (and associated phenotypes)
- two haplotypes with very different phenotypes are both present at relatively high levels (relative to the other 5 haplotypes)
- there are more "intermediate-frequency variants" than could reasonably be expected if selection was neutral
- frequencies differences around the world don't correlate with known subpopulation distributions (i.e. can't blame differences on founder effect or bottleneck
- Don't know why there is balancing selection for the 2 alleles - either both tasting and nontasting have advantages or the nontasting allele encodes a different function (taste other compounds).
- MY NOTE: The second idea seems less likely as 3D modeling (Floraino 2006) predicts no change in the ligand binding site
Here is the paragraph from Lauri's lab manual
The heritability of PTC tasting ability was first identified in 1932 (Blakeslee 1932; Fox 1932). Until recently, the ability to taste PTC was thought to be inherited as a simple, dominant Mendelian trait (Fox 1932). For decades people were classified as either “tasters” or “nontasters”, even as evidence accumulated that there is a more continuous distribution in tasting ability. The riddle of PTC tasting was partially solved when the gene responsible was identified (Kim et al. 2003). Sequence analysis of the PTC gene (TASR38) has identified 5 nucleotide positions that can vary in sequence (such variations are referred to as Single Nucleotide Polymorphisms or SNPs)(Wooding et al. 2004). Although the 5 SNPs can theoretically combine to form 32 distinct haplotypes, so far only 7 haplotypes have been observed, and greater than 97% of all PTC sequences are accounted for by only 3 haplotypes (Wooding et al. 2004; Kim et al. 2003).
Let's break it down
The heritability of PTC tasting ability was first identified in 1932 (Blakeslee 1932; Fox 1932).
Note that both papers look at more than just the PTC tasting ability. Fox investigate the taste of several chemicals related to PTC; however, I don't need to include this in my paragraph because it is not pertinent to the point I want to make (that we have been studying this taste since 1932).
The riddle of PTC tasting was partially solved when the gene responsible was identified (Kim et al. 2003).
The paper I am citing contains the detailed description of how the gene involved was identified and cloned. I'm not discussing how to identify genes so I don't need to talk about those details. I do, however, want my audience to know how I know that TAS2R38 encode PTC tasting.