AQA A-Level Biology: Mutations

A mutation is a change in the base sequence of DNA, and because that sequence codes for proteins, a mutation can change a protein, sometimes enough to stop it working. This guide covers the different types of mutation, how they alter a protein, and why, despite all this, many mutations have no effect and a few are even beneficial. The key is to follow the change from the DNA all the way through to the protein's shape.

What a mutation is

A gene mutation is a change in the base sequence of DNA. Mutations can arise spontaneously during DNA replication, when bases are copied incorrectly. Their rate is increased by mutagenic agents (mutagens), such as ultraviolet light and alpha particles.

The types of mutation

There are several kinds of mutation, defined by what happens to the bases.

• Substitution: one base is replaced by a different base.
• Addition: one or more bases are added to the sequence.
• Deletion: one or more bases are removed from the sequence.
• Duplication: a sequence of bases is repeated.
• Inversion: a sequence of bases is removed and rejoins at the same place, but in reverse order.
• Translocation: a sequence of bases is moved to a different location, on the same or a different chromosome.

How a mutation changes a protein

A mutation can lead to a non-functional protein or enzyme through a chain of consequences that runs from the gene to the protein's shape.

• It changes the sequence of base triplets in the DNA, so it changes the sequence of codons on the mRNA.
• This changes the sequence of amino acids in the polypeptide.
• A different amino acid sequence changes where the hydrogen bonds, ionic bonds and disulfide bridges form.
• This changes the tertiary structure of the protein.
• In an enzyme, the active site changes shape, so the substrate can no longer bind and no enzyme-substrate complex forms.

Note the precise wording: a mutation does not create new amino acids (they already exist in the cell), and it changes the tertiary structure, which is what the change in bonding produces.

Frameshifts

The genetic code is read in non-overlapping triplets from a fixed starting point, so adding or removing bases can throw the whole reading out of step. A frameshift happens when a mutation changes the number of bases by an amount not divisible by three.

From the point of the mutation onwards, every triplet is read differently, so all the codons downstream change. This usually alters most of the amino acid sequence after the mutation, so the effect on the protein is severe. Addition and deletion mutations cause frameshifts, whereas a substitution, which swaps one base for another without changing the total number, does not.

Mutations can also produce shorter polypeptides. A deletion or translocation can remove a codon, so an amino acid is missing, and any type of mutation can create a premature stop codon, which ends translation early and leaves the rest of the polypeptide unmade.

Why not all mutations are harmful

It is a common mistake to assume every mutation damages a protein. In fact many have no effect at all, for two main reasons.

• The genetic code is degenerate: most amino acids are coded for by more than one triplet. So a substitution may change a codon to one that still codes for the same amino acid, leaving the protein unchanged. This is a silent mutation.
• Some mutations occur in introns, the non-coding sections of a gene, which are removed during splicing and so never affect the amino acid sequence.

Even when the amino acid sequence does change, the result is not always harmful. The change may not alter the tertiary structure enough to matter, or it may improve the protein, producing a new, advantageous allele that gives the organism a selective advantage. This is exactly the raw material that natural selection acts on.

How this fits together

Mutations are the ultimate source of genetic variation, and their effect depends entirely on how, and whether, they change a protein. But a cell does not express all of its genes at once. Which genes are switched on, and when, is controlled tightly, and that begins with how unspecialised cells become specialised, the subject of the stem cells and cell differentiation guide.