Mutations are changes in the DNA sequence of the genome. These are caused by a lot of factors including unrepaired damage (the failure of the DNA repair mechanism), errors in replication, or errors during synthesis. Some mutations include substitution, deletion, insertion, inversion, translocation, and chromosomal rearrangements.
Proteins are essentially derived from the genetic code. The DNA is translated into an RNA in a process called transcription. The RNA sequence is then 'read' in a process called translation in order to synthesize the proteins. Each amino acid in a protein is controlled by three RNA residue (codons). For instance, a UUU sequence in the RNA will result to a Phenylalaine, while a GGU a Glycine. Some combinations yield the same amino acids, but no two amino acids correspond to the same codon. There are also stop and start codons which dictate where translation starts and ends.
Because of this, a single change in the DNA sequence could result to various changes in the protein level:
- Silent mutation is when a mutation occurs but it has no effect on the protein. As mentioned multiple codons may result to the same amino acid -- e.g. UUU and UUC both correspond to Phe, so a U to C mutation won't have an effect.
- Missense mutation on the other hand is when the substitution results to a different amino acid -- e.g. from UUU a mutation occurs and gives UUA. This results to production of Leucine instead of Phenylalanine.
- Nonsense mutation, on the other hand, is when a stop codon replaces what is supposed to be a codon for an amino acid. When a stop codon is reached, the translation is stopped prematurely and the protein is not formed.
- Frameshift mutation is when an extra nucleic acid is inserted or deleted. This has severe effects as it will not only change one amino acid, but the rest of the remaining amino acids will be affected.
The effects of these on function can be divided into two categories: loss of function, or gain of function. Let's start with the latter. It is possible that a mutation could increase the function of a protein, or it could also acquire a new function due to changes in its amino acid sequence. For example, a 32-base deletion in CCR5 confers HIV resistance to humans with that mutation. Usually, however, we get loss of function. The change in at a single point could affect the entire function of the protein. For instance, a single change in residue 156 of the human HLA-B35 from arginine to lysine removes the ability of the T cell receptor SB27 to bind to it. It is also possible that a change in some residues would change the polarity of the protein, and hence reduce its function. Some mutations, as mentioned, result to nonsense mutations, which essentially stop protein synthesis prematurely.