Question

There are as many as 200 common variations in the MC1R gene that are associated with differences in skin and hair color and several others associated with pathological conditions associated with a lack of (albinism) or loss of (vitiligo) pigmentation.

9a) Red hair and fair skin is associated with a variant located in the second intracellular loop of the receptor (depicted as a red star on the light side of figure 2). Compare the most common, wildtype, mRNA sequence for the MC1R gene with that of the redhead variant. (5 marks)  

1. Translate the mRNAs below to identify the mutation and its effect. Clearly identify the difference by circling the affected amino acid(s). Answer the subsequent questions to identify how this might result in a change in pigmentation.

Wildtype mRNA             478 – GCG  CGG  CGA  GCC  GUU – 493

                                           N’ ____   ____   ____   ____   ____    C’  

                                        

Redhead mRNA         478 – GCG UGG CGA GCC GUU - 493

                                      N’ ____   ____   ____   ____   ____    C’  

2. Does the mutation in part (i) affect the chemistry of the amino acid(s)? If so, how?

3. How could the mutation in part (i) result in a change in pigmentation in affected individuals? *Hint - think about the mechanism of action of this receptor.

   

9b) You are studying the genome of a family that experiences albinism (lack of pigmentation). You do not observe any of the known mutations that cause albinism but identify a tRNA gene that has undergone a mutation such that its anticodon now recognizes the stop codon of the MC1R gene. Describe the impact this would have on the MC1R protein produced and why this might lead to an absence of pigmentation. (2 marks)

Answer 1

Ans: 1) Translated wild type mRNA: Ala-Arg-Arg-Ala-Val.

Translated Redhead mRNA: Ala-Trp-Arg-Ala-Val

So as we can see from the amino acid sequence that the only difference between wild type and redhead type is the exchange of Arg at 2nd position to Trp.

i) Yes the mutation change the affect the chemistry of amino acid because as we can see that Arg in wild type is exchanged with Trp in redhead type and as we know that Tryptophan is a neutral non-polar amino acid and Arginine is a positive charged polar amino acid so this mutation will affect the overall polarity of the protein and thsi will affect the function of the protein in the cell.

ii) The MC1R gene provides instructions for making a protein called the melanocortin 1 receptor. This receptor plays an important role in normal pigmentation. he receptor is primarily located on the surface of melanocytes, which are specialized cells that produce a pigment called melanin. Melanin is the substance that gives skin, hair, and eyes their color. So from the above we can see that the overall polarity of the receptor is affecting because of the mutation and because of this the receptor is not able to bind the melanin as melanin is water soluble and polr substance and if melanin does not binds to the receptor pigmentation will not occur in the cell.

2) The scenario explained in the question is basically a non sense mutation. A nonsense mutation is the substitution of a single base pair that leads to the appearance of a stop codon where previously there was a codon specifying an amino acid. The presence of this premature stop codon results in the production of a shortened, and likely nonfunctional, protein. As described in the question that the mutated tRNA anticodon recognizes a stop codon and this will leads to premature stopping of translation. This will leads to the formation of a truncated melanocortin 1 receptor and this non functonal receptor will not be able to bind the substrate and this will leads to albinism.