DNA Mutations

The order of DNA nucleotide in DNA is what makes you different from everything else. These nucleotides are read together in groups of three, known as the triplet code. The nucleotides of the triplet code determine which amino acid is added to the growing protein chain. The protein, the final product of the gene, is determined by the amino acids that make it up. So, changing a single nucleotide can possibly change the function of a gene.

However, each triplet code isn’t exactly unique. DNA is known as a degenerate code. This isn’t an insult, it just means the same amino acid can be produced from two or more different triplet codes. This explains why we have 64 different combinations of triplet code (4 nucleotides to chose from; A,U,G,C and 3 slots = 43 =64) but only have 20 amino acids.

The degeneracy of the triplet code of DNA means that mutations to DNA doesn’t always necessarily cause a problem.

genetic-code

Replacing a single nucleotide doesn’t always mean that there will be an amino acid change. For example, substituting the final C of CUC for A still adds a leucine to the growing protein. This is known as a silent mutation, because the mutation has had no effect on the protein produced, effectively meaning that it is not clear that the mutation has even happened.

This isn’t always the case though. Replacing the first C of CUC for G causes the amino acid used to change from leucine to valine. This is known as a missense mutation, because the change of a single nucleotide has know produced a protein that is different to the intended product.

Another type of mutation is a nonsense mutation. A nonsense mutation causes protein production to stop unexpectedly. Amino acids are no longer added to the chain when the triplet code is one of three sequences. A substitution of a single nucleotide can sometimes cause an amino acid to be replaced by a stop codon. For example, UAC of tyrosine can become a UAA stop codon by swapping the final C for A.

All the mutations discussed so far have happened because a single nucleotide has been swapped for another. Nucleotides can also be lost during DNA replication, and we call these mutations deletions.

If a whole triplet code (three amino acids) is deleted, the protein produced will be identical except for one missing amino acid. This can have complications as it changes the way the protein folds into shape (and therefore functions), but the overall change is usually minimal.

However, if one or two nucleotides are deleted, a frameshift occurs. A frameshift is caused because the starting point for each triplet code has changed. This means the deletion of these nucleotides has a knock on effect on all other triplet codes further down the DNA molecule. This means the amino acids added changes, meaning the final protein can be completely different.

How frameshift works:

AUG UUA UCA CUA UCC AAC UAC …

Met, Leu, Ser, Leu, Ser, Asn, Thr

The red U is deleted causing a frameshift.

 

AUG UAU CAC UUG CCA ACU AC…

Met, Tyr, His, Leu, Pro, Thr, ..

The orange amino acids have changed. 

This different protein produced can be non-functional, or can perhaps have a function that is completely unrelated to the intended protein.

As you can see, almost all amino acids have changed. Leucine kept its place due to the degeneracy of the triplet code (CUA and UUG both encode leucine). What didn’t happen in this case, is that the frameshift creates a stop codon.

An example could be that a frameshift of one nucleotide:

… CUG UUA GAC CAG

… Leu, Leu, Asp, Gln

Becomes

… CGU UAG ACC AG…

Arg, STOP.

This single nucleotide deletion is therefore also defined as a nonsense mutation.

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