What is a mutation?
- Mutations involve a change in the base sequence of the DNA
- They can arise spontaneously during DNA replication, or they can be caused by mutagenic agents
- Due to the degenerate nature of the genetic code, not all base substitutions cause a change in the sequence of encoded amino acids.
- This means that there are multiple codons which can all code for the same amino acid, so if there is a single base change mutation it might still code for the same amino acid
- E.g. UCU, UCC, UCA, and UCG all code for the amino acid Serine
- If the mutation is in the intron (outside the coding region), it also won’t cause a change to the encoded protein.
Types of Gene Mutation
What you need to know (from the AQA specification)
What you need to know (from the AQA specification)
Gene mutations might arise during DNA replication. They include addition, deletion, substitution, inversion, duplication and translocation of bases.
The below animations go through the different types of mutations you need to be aware of, breaking it down by:
- DNA sequence change
- Resulting mRNA change (transcribed from DNA template strand)
- Amino acid change (translated from mRNA)
Addition
- Inserting an additional nucleotide into the DNA code
- This causes a frameshift mutation, shifting the entire sequence to the right
- Note: If we inserted 3 nucleotides (or multiples of 3) it wouldn’t cause frameshift mutation, but would still produce a different polypeptide chain
Addition mutation shown in the animation
Original sequence
| Codon 1 | Codon 2 | Codon 3 | |
|---|---|---|---|
| DNA template (3’→5’) | A T A | G C A | T G A |
| mRNA (5’→3’) | U A U | C G U | A C U |
| Amino acid | Tyr | Arg | Thr |
After addition: Insert G after “AT”
| Codon 1 | Codon 2 | Codon 3 | |
|---|---|---|---|
| DNA template (3’→5’) | A T G | A G C | A T G |
| mRNA (5’→3’) | U A C | U C G | U A C |
| Amino acid | Tyr | Ser | Tyr |
The inserted base shifts the reading frame right, changing all downstream amino acids.
Deletion
- Deletion works in a similar way to addition; it deletes a nucleotide from the base sequence
- This causes a frameshift mutation, shifting the entire sequence to the left
Deletion mutation shown in the animation
Original sequence
| Codon 1 | Codon 2 | Codon 3 | |
|---|---|---|---|
| DNA template (3’→5’) | A T A | G C A | T G A |
| mRNA (5’→3’) | U A U | C G U | A C U |
| Amino acid | Tyr | Arg | Thr |
After deletion: Remove the 3rd base (A)
| Codon 1 | Codon 2 | Codon 3 | |
|---|---|---|---|
| DNA template (3’→5’) | A T A | G C A | T G A |
| mRNA (5’→3’) | U A C | G U A | C U … |
| Amino acid | Tyr | Val | … |
The deleted base shifts the reading frame left, changing all downstream amino acids.
Substitution
- When a DNA nucleotide base is replaced for another (e.g C is replaced by A)
- This could cause the following effects:
- Missense mutation: Change in the encoded amino acid
- This would cause a change in the polypeptide chain (protein)
- Nonsense mutation: Creation of STOP codon, which prematurely stops translation
- Silent mutation: No change to amino acid encoded as the genetic code is degenerate
- Even though the codon has changed, different codons can code for the same amino acid
- Missense mutation: Change in the encoded amino acid
Substitution mutations shown in the animation
Original sequence
| Codon 1 | Codon 2 | Codon 3 | |
|---|---|---|---|
| DNA template (3’→5’) | A T A | G C A | T G A |
| mRNA (5’→3’) | U A U | C G U | A C U |
| Amino acid | Tyr | Arg | Thr |
Silent substitution (A → G in codon 1)
| Codon 1 | Codon 2 | Codon 3 | |
|---|---|---|---|
| DNA template (3’→5’) | A T G | G C A | T G A |
| mRNA (5’→3’) | U A C | C G U | A C U |
| Amino acid | Tyr | Arg | Thr |
Codon changes (UAU → UAC), but still codes for Tyr. No effect on protein.
Missense substitution (G → T in codon 2)
| Codon 1 | Codon 2 | Codon 3 | |
|---|---|---|---|
| DNA template (3’→5’) | A T A | T C A | T G A |
| mRNA (5’→3’) | U A U | A G U | A C U |
| Amino acid | Tyr | Ser | Thr |
Codon changes (CGU → AGU), so Arg → Ser. Different amino acid in protein.
Nonsense substitution (A → T in codon 1)
| Codon 1 | Codon 2 | Codon 3 | |
|---|---|---|---|
| DNA template (3’→5’) | A T T | G C A | T G A |
| mRNA (5’→3’) | U A A | C G U | A C U |
| Amino acid | STOP | — | — |
Creates a stop codon (UAA). Translation ends early, producing a truncated protein.
Duplication of bases
- One or more bases are repeated.
- This causes a frameshift mutation, shifting the entire sequence to the right.
Duplication mutation shown in the animation
Original sequence
| Codon 1 | Codon 2 | Codon 3 | |
|---|---|---|---|
| DNA template (3’→5’) | A T A | G C A | T G A |
| mRNA (5’→3’) | U A U | C G U | A C U |
| Amino acid | Tyr | Arg | Thr |
After duplication: 3rd base (A) is duplicated
| Codon 1 | Codon 2 | Codon 3 | |
|---|---|---|---|
| DNA template (3’→5’) | A T A | A G C | A T G |
| mRNA (5’→3’) | U A U | U C G | U A C |
| Amino acid | Tyr | Ser | Tyr |
The duplicated base shifts the reading frame right, changing all downstream amino acids.
Inversion of bases
- Occurs when a segment of DNA breaks off from a chromosome, flips 180 degrees, and reinserts itself in the reverse order, changing the sequence of genetic bases.
- In this example (in animation) it causes a missense mutation where the encoded amino acid changes.
Inversion mutation shown in the animation
Original sequence
| Codon 1 | Codon 2 | Codon 3 | |
|---|---|---|---|
| DNA template (3’→5’) | A T A | G C A | T G A |
| mRNA (5’→3’) | U A U | C G U | A C U |
| Amino acid | Tyr | Arg | Thr |
After inversion: Codon 2 (GCA) is flipped to ACG
| Codon 1 | Codon 2 | Codon 3 | |
|---|---|---|---|
| DNA template (3’→5’) | A T A | A C G | T G A |
| mRNA (5’→3’) | U A U | U G C | A C U |
| Amino acid | Tyr | Cys | Thr |
The segment is reversed (GCA → ACG), changing the codon and resulting amino acid.
Translocation of bases
- Occurs when a segment of DNA breaks off from one chromosome, and reinserts itself in a new chromosome.
- These can have a significant effect on gene expression, resulting in different phenotypes.
- Animation below shows how translocation works - you don’t need to be aware of the difference between reciprocal and non-reciprocal translocation; these are just for illustrative purposes.
Effects of Gene Mutations
What you need to know (from the AQA specification)
What you need to know (from the AQA specification)
Gene mutations occur spontaneously. The mutation rate is increased by mutagenic agents. Mutations can result in a different amino acid sequence in the encoded polypeptide. - Some gene mutations change only one triplet code. Due to the degenerate nature of the genetic code, not all such mutations result in a change to the encoded amino acid. - Some gene mutations change the nature of all base triplets
Above, we have seen different types of mutations and how they can have an effect on the encoded amino acid. The table below summarises these.
| Mutation type | Frameshift? | Effect |
|---|---|---|
| Missense (substitution) | No | One base is substituted → different amino acid encoded |
| Silent (substitution) | No | One base is substituted, amino acid stays the same (degenerate code) |
| Nonsense (substitution) | No | One base is substituted, creates a stop codon → early termination |
| Insertion | Yes* | Base(s) added, reading frame shifts right → downstream amino acids change |
| Deletion | Yes* | Base(s) removed, reading frame shifts left → downstream amino acids change |
| Duplication | Yes* | Base(s) repeated, reading frame shifts right → downstream amino acids change |
| Inversion | No | Amino acids may change within the inverted segment |
| Translocation | No | Gene disruption, altered gene expression, changes in phenotype |
*Note: If we inserted 3 nucleotides (or multiples of 3) it wouldn’t cause frameshift mutation, but would still produce a different polypeptide chain
Tip
Understand how the mutation works, and then what effect this could have on the encoded amino acid sequence
Causes of Gene Mutations
Mutations happen spontaneously and as a result of errors in DNA replication. The rate of mutations can be increased through mutagenic agents.
Mutagenic agents examples
- High-energy radiation
- UV light
- Gamma rays
- X-rays
- Chemicals
- Alkylating Agents (e.g. mustard gas), add alkyl groups to DNA bases
- Benzene - found in tobacco smoke, inactivates tumour suppressor gene
- Biological
- Viruses: HPV virus, Hepatitis B/C
- Bacteria: Helicobacter pylori
Are mutations always harmful?
Are mutations always harmful?
- Mutations can be harmful to the cells, causing proteins that don’t function as expected, and can cause cancer.
- An important distinction is that mutagenic agents don’t necessarily cause cancer; they cause mutations which may or may not cause cancer. Carcinogens are agents known to cause cancer.
- Sometimes mutations can be beneficial
- They can produce genetic diversity for natural selection and speciation
How this topic is tested
This analysis is based on past paper data from 2017 to 2025. It is intended for interest only and is not predictive of what will appear in future papers.
- Tested in 6 of 9 years (2017–2025): 11 question parts worth 29 marks.
- 34th most-examined topic overall by marks, 5th in Unit 8.
Marks by year
Most-tested spec points
- Effects of Mutations on the Polypeptide: tested in 6 parts (17 marks)
- Types of Gene Mutation: tested in 4 parts (8 marks)
Also links to: Oncogenes, Tumour Suppressor Genes & Oestrogen, Evaluating Cancer Evidence & Treatment, Levels of Protein Structure.
Maths and practical skills
- Units and standard form (MS 0.2): e.g. 2025 P2 Q8.1
- Percentages, ratios and fractions (MS 0.3): e.g. 2025 P2 Q8.1
- Evaluating results and conclusions (PS 2.3): e.g. 2019 P3 Q4.2
Exam Questions
Duchenne muscular dystrophy can be caused by mutations in the DMD gene, which codes for the protein dystrophin. Dystrophin is not an enzyme. In some people, the mutation is an inversion.
Explain how an inversion mutation can lead to the production of non-functional dystrophin.
(4 marks)
Hint
What exactly is reversed in an inversion? Follow the effect from the DNA to the amino acids, then to the bonds and the shape of the protein.
Mark Scheme
- The sequence of DNA bases is reversed (inverted) (1 mark)
- So the sequence of amino acids (primary structure) changes (1 mark)
- So hydrogen, ionic or disulfide bonds form in different places (1 mark)
- So the tertiary structure changes (1 mark)
Also accepted / rejected
Tips
- Say it’s the DNA base sequence that is inverted
- Then the amino acid sequence changes, so bonds form in different places and the tertiary structure changes
- Dystrophin isn’t an enzyme, so don’t mention an active site
In a study of a mouse embryo, 2.0 × 10⁻⁷ % of the genome of one cell had changed because of mutations.
You can assume that:
- the mouse genome contains 2.7 × 10⁹ nucleotides
- on average, 0.9 mutations happen in each cell cycle
- each cell cycle lasts 24 hours.
Calculate the age of the embryo in days.
Show your working.
Answer = ________ days
(2 marks)
Hint
Turn the percentage into a number of mutated nucleotides. How many cell cycles would produce that many mutations?
Mark Scheme
6 days (2 marks)
Working:
- Number of mutations: (2.0 × 10⁻⁷ ÷ 100) × 2.7 × 10⁹ = 5.4
- Number of cell cycles: 5.4 ÷ 0.9 = 6
- Each cycle is 24 hours, so 6 cycles = 6 days
If the answer is wrong, 1 mark for any of:
- 600 or another power of ten (not dividing the percentage by 100)
- 144 (multiplying by 24)
- 4.86 (multiplying by 0.9 instead of dividing)
- 5.4 (not dividing by 0.9)
Tips
- Divide the percentage by 100 before using it
- Divide the number of mutations by the mutations per cycle to get the number of cycles
- Each cycle is one day, so don’t multiply by 24
Also accepted
Not accepted