Genetic Mutations (AQA A Level Biology): Revision Note

Genetic mutations

• A gene mutation is a change in the sequence of base pairs in a DNA molecule that may result in an altered polypeptide

• Mutations occur continuously and at random

• The DNA base sequence determines the sequence of amino acids that make up a protein; therefore, mutations in a gene can sometimes lead to a change in the polypeptide that the gene codes for

• Most mutations do not alter the polypeptide, or only alter it slightly, so that its structure or function is not changed

  • This is because the genetic code is degenerate 

• There are different ways that a mutation in the DNA base sequence can occur:

Deletion of nucleotides

• A deletion mutation occurs when a nucleotide (and therefore its base) is randomly deleted from the DNA sequence

• A deletion mutation changes the amino acid that would have been coded for

• These mutations have a knock-on effect by changing the triplets of three bases further on in the DNA sequence

  • This is sometimes known as a frameshift mutation

• This may dramatically change the amino acid sequence produced from this gene and therefore the ability of the polypeptide to function

Substitution of nucleotides 

• A mutation that occurs when a base in the DNA sequence is randomly swapped for a different base

• Unlike a deletion mutation, a substitution mutation will only change the amino acid for the triplet in which the mutation occurs; it will not have a knock-on effect

• Substitution mutations can take three forms:

  • Silent mutations – the mutation does not alter the amino acid sequence of the polypeptide because many codons code for the same amino acid as the genetic code is degenerate

  • Missense mutations – the mutation alters a single amino acid in the polypeptide chain (e.g., sickle cell anaemia is a disease caused by a single substitution mutation changing a single amino acid in the sequence)

  • Nonsense mutations – the mutation creates a premature STOP codon, causing the polypeptide chain produced to be incomplete and therefore affecting the final protein structure and function (e.g., cystic fibrosis is a disease caused by a nonsense mutation, although this is not always the only cause)

 The effect of gene mutations on polypeptides 

• Most mutations do not alter the polypeptide or only alter it slightly, so that its appearance or function is not changed

• However, a small number of mutations code for a significantly altered polypeptide with a different shape

• This may affect the ability of the protein to perform its function. For example:

  • if the shape of the active site on an enzyme changes, the substrate may no longer be able to bind to the active site

  • a structural protein (like collagen) may lose its strength if its shape changes

Mutagenic agents

• There are natural mechanisms that take place within cells to ensure the accuracy of DNA replication

  • These mechanisms involve proofreading and repairing damaged DNA

• When the mutation rate of a cell rises to above a normal (usually low) rate, then these mechanisms become ineffective

• Mutagenic agents are environmental factors that increase the mutation rate of cells

• Examples include:

  • high-energy radiation such as UV light

  • ionising radiation such as X-rays

  • toxic chemicals such as peroxides