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. Compare the most common, wildtype, mRNA sequence for the MC1R gene with that of the redhead variant.

i) 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 GTT - 493

N’ ____ ____ ____ ____ ____ C’

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

iii) 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.

Answer 1

Wild type protein - N - Ala Arg Arg Ala Val - C

Readhead protein - N - Ala Trp Arg Ala Val - C

ii- Arginine is a charged amino acid and tryptophan is an aromatic amino acid. One type of amino acids is mutated to another type. So mutation will affect the chemistry of protein

iii - Arginine is a positively charged polar amino acid and tryptophan is an aromatic amino acid. If arginine is present in the receptor then it will interact with the polar or negatively charged amino acid. On the other hand, Tyrpotophan due to hydrophobic nature prefers hydrophobic amino acid. If arginine is mutated to tryptophan then due to its nature it will disrupt the overall protein structure and make the receptor non-functional.

B - Stop codons are not recognized by any tRNA.

Genomic study reveals that there was no mutation in the gene of MC1R protein, but there was a mutation in the anticodon of tRNA such that it starts to recognize stop codon as amnio acid coding codon. Due to mutation, now translation will not stop at the stop codon and continue till ribosome encounter another stop codon. As a result of it, many amino acids will be added to the MC1R protein. It might possible that these amino acids start interacting with the amino acids that are crucial for MC1R such that MC1R doesn't function at all.

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