The diagram provided shows a simplified outline of the different types of gene
mutations that can occur in a strand of DNA. Which diagram, 1, 2, or 3, demonstrates a substitution mutation?
This question is asking us to remember what a substitution mutation is. Let’s discuss a few different types of mutations before we return to the diagram and
try to answer our question.
In order for a gene in DNA to be converted into a protein, it needs to go through a
couple of steps. The first step is called transcription. Here, the DNA sequence is copied to make an mRNA transcript. The sequence of nucleotides in mRNA can then be converted into a sequence of amino
acids during translation to form a polypeptide, which can then fold into a
Let’s look at how mRNA can be translated into a protein sequence. Here’s a nine-nucleotide sequence of mRNA. When this sequence is translated, it’s done so in three-nucleotide segments called
codons. These codons correspond to specific amino acids. So, the codon AUG corresponds to the amino acid methionine for example. These amino acids are matched to the correct codons during translation, and each
codon is read consecutively. This is sometimes called the reading frame. This mRNA sequence is copied from the DNA sequence, which you can see here. Remember, uracil in RNA is replaced by thymine in DNA.
A genetic mutation is a change in the nucleotide sequence in DNA. There’s different types of mutations that are possible, so let’s look at each of them
Insertion mutations insert a nucleotide into a DNA sequence. Notice how we now have an additional nucleotide, a thymine, inserted into our DNA
sequence. So now, there’s 10 nucleotides instead of nine. This mutation will be carried over into the mRNA, as we can see here.
Notice that the last two codons are now different from what they were previously. Because the sequence of the codons have changed, this changes the amino acid sequence
too. Also notice how multiple amino acids can be impacted by a single-insertion
mutation. This is because the reading frame has changed from the point of the insertion
Now, let’s reset our sequence and see what happens in a deletion mutation. Here the nucleotide is deleted, so all the nucleotides in front of this mutation will
be shifted over. You can see that in the DNA sequence here. Notice how there’s eight nucleotides instead of nine now. You can see this carried over to the mRNA sequence as well, which changes the codons
and therefore changes the amino acid sequence in the protein. This kind of mutation also causes a frameshift, just like the insertion mutation.
Let’s again reset our sequence and look at the final type of mutation, a substitution
mutation. Here thymine is substituted for a guanine. Notice how we still have nine nucleotides in total, which again is copied over into
mRNA and changes the codon. Now the amino acid proline replaces histidine. Notice how the two amino acids on either side aren’t affected. This is because there was no frame shift like in the insertion or deletion
mutations. So, only a single amino acid is usually affected with a substitution mutation.
Now, let’s look at our provided diagram and try to figure out which one is a
substitution mutation. The easiest way to do this is to count the number of nucleotides in the mutated
sequence. In the original sequence, we have 12 nucleotides. In mutation 1, there’s 11 nucleotides, so this is a deletion mutation. In mutation 3, there’s 13 nucleotides, so this is an insertion mutation. And in mutation 2, there’s 12 nucleotides. We can see the substitution at position six, where a cytosine in the original
sequence was substituted for a guanine in the mutation. Therefore, diagram 2 indicates a substitution mutation.