Types of mutations

Single base substitutions

A single nucleotide base becomes replaced by another. These single base changes are also called point mutations. If a purine (a, t) replaces a purine or a pyrimidine (c, g) replaces a pyrimidine, it is called a transition. If a purine replaces a pyrimidine or vice-versa, the substitution is called a transversion.

Missense mutations -


In a missense mutation, the new base alters a codon resulting in a different amino acid being incorporated into the protein chain. This is what happens in sickle cell anaemia. The 17th nucleotide of the gene for the beta chain of haemoglobin is changed from an 'a' to a 't'. This changes the codon from 'gag' to 'ggt' resulting in the 6th amino acid of the chain being changed from glutamic acid to valine. This apparently trivial alteration to the beta globin gene alters the quaternary structure of haemoglobin, which has a profound influence on the physiology and wellbeing of the individual.The picture on the right shows an example of a missence mutation, a substitution of 'a' in the second codon to 'g' leads to an amino acid substitution of glutamine (Q) to arginine (R).


Nonsense mutations -

In a nonsense mutation, the new base changes a codon that specified an amino acid into one of the stop codons (taa, tag, tga). This will cause translation of the mRNA to stop prematurely and a truncated protein to be produced. This truncated protein will be unlikely to function correctly. Nonsense mutations occur in between 15% to 30% of all inherited diseases including cystic fibrosis, haemophilia, retinitis pigmentosa and duchenne muscular dystrophy. The picture on the right shows an example of a nonsense mutation, where 'c' in the second codon is changed to 't'. In the normal nucleotide sequence the second codon 'cag' codes for glutamine (Q) whilst in the mutated second codon 'tag' codes for Stop leading to premature termination of the protein.


Silent mutations -


Silent mutations are those that cause no change in the final protein product and can only be detected by sequencing the gene. Most amino acids that make up a protein are encoded by several different codons (see genetic code). So, if for example, the third base in the 'cag' codon is changed to an 'a' to give 'caa', a glutamine (Q) would still be incorporated into the protein product, because the mutated codon still codes for the same amino acid. These types of mutations are 'silent' and have no detrimental effect.

Splice site mutations -


Introns must be spliced from mRNA to produce the correct protein. This process must be carried out very accurately and it is guided by the nucleotide signals at the splice sites. If a mutation alters these signals, the intron may not be removed and an incorrect protein will be produced.