Question

You have a small gene that encodes the following amino acid: N-MET-ASP-SER-VAL-ALA-ARG-PHE-MET-TRP-C. There is a single mutation in the DNA that causes a change in the amino acid sequence to: N-MET-VAL-GLN-TRP-PRO-ASP-LEU-CYS-GLY-C.

a) What kind of mutation is this? Explain. (2 points)

b) Indicate the DNA sequence (coding strand) of the gene. Show the original DNA sequence then the mutated sequence.

Wild type DNA:

Mutant DNA:

You have another mutation (a different mutation from the one described in parts a and b) in the gene that causes this amino acid sequence to be made: N-MET-ASP-SER-LEU-ALA-ARG-PHE-MET-TRP-C

c) What kind of mutation is this? (1 point)

d) Describe the change that took place in the DNA sequence to give this altered protein sequence. (1 point; note that you will need the answer to b to answer this question, and if you like you can indicate on the wild type DNA in question b where the mutation is located)

In yet another strain, you have yet another mutation that gives this protein sequence: N-MET-ASP-SER-VAL-ALA-C

e) What kind of mutation is this? (1 point)

f) Describe the change that took place in the DNA sequence to cause this altered protein sequence. (1 point; note that you will need the answer to b to answer this question, and if you like you can indicate on the wild type DNA in question b where the mutation is located)

Answer 1

First of all, if you want to get the DNA sequence (the actual wild type gene) from the above peptide sequence then quickly convert it to the ONE LETTER amino acid name which is shown below:

N-terminal-(MDSVARFMW)-C-terminal or NH2- MDSVARFMW-COOH or just MDSVARFMW (this is how you can denote a peptide sequence).

Now, you can go to EMBOSS Backtranseq website to get the wild type DNA sequence out of your given peptide sequence. The result is as follows:

Wild type DNA sequence: ATG GAC AGC GTG GCC AGG TTC ATG TGG

and then you can get the mutated DNA sequence by following the same protocol by providing the sequence MVNWPDLCG.

Mutant DNA sequence: ATG GTG AAC TGG CCC GAC CTG TGC GGC

So, if you start comparing these two sequences, then you will find that there are several changes happened which resulted in a massive difference in the peptide sequence as well. After looking at the data very carefully, you will find that Purine and pyrimidines have been changed to either Purine or pyrimidines (i.e. A ->T , T ->A, C ->G, G ->A, C ->T). This type of mutation is called 'Base Substitution'.

Base substitution or point mutation is divided into two subparts which are known as 'Transition' and 'Transversion'

Transition: When a purine base is converted to another purine (A to T or T to A) and when pyrimidine is converted to another pyrimidine (G to C or C to G).

Transversion: This type of mutation replaces a purine with a pyrimidine or a pyrimidine with a purine.

In the next mutation, the peptide sequence was almost similar only one amino acid got changed (Val to Leu)

The mutated gene is: ATG GAC AGC CTG GCC AGG TTC ATG TGG

Here only one base pair got altered, which resulted a single amino acid change within the whole peptide sequence. This type of mutation is called 'Missense' mutation.

Lastly, The mutation shortened the peptide sequence (MDSVA) by four amino acid (RFMW got missing). But the gene that code the amino acid after Ala is AGG which will not represent a stop codon in the mRNA. So this is not a 'Nonsense' mutation but a 'Deletion' mutation.