Gene Mutations

SPEC 3.4.3 - GENETIC INFORMATION

Gene & Chromosome Mutations

Base substitution, deletion, frameshift, mutagenic agents & chromosome non-disjunction

Gene Mutation

A change in the base sequence of DNA.

Gene mutations arise spontaneously during DNA replication — when a base is incorrectly incorporated and the error is not corrected. They can also be caused by mutagenic agents that increase the rate at which mutations occur.

Types required at 3.4.3

Base deletion — a base is removed

Base substitution — one base is replaced by another

Key characteristics

Spontaneous and random

Can occur in any gene

Rate increased by mutagenic agents

Most are harmful or neutral; very few are beneficial

Examiner Alert

Mutations are random — they are not directed by the environment. A mutagenic agent increases the rate of mutation but does not direct which mutations occur or whether they will be beneficial. Never say the environment "causes" a specific beneficial mutation.

Base Substitution

In a base substitution, one base is replaced by a different base. Only the codon containing the substituted base is directly affected — all other codons are unchanged.

OutcomeWhat happensEffect on protein

Silent (synonymous)The new codon codes for the same amino acid — possible due to the degenerate genetic codeNo change — protein unaffected

MissenseThe new codon codes for a different amino acidOne amino acid changed — primary structure altered; tertiary structure may change; protein may be non-functional

NonsenseThe new codon is a stop codon (UAA, UAG or UGA)Translation terminates early — truncated, shorter polypeptide; usually non-functional

Why silent mutations exist

The genetic code is degenerate — most amino acids are coded for by more than one codon. A substitution at the 3rd base of a codon very often produces a synonymous codon. This is the degenerate nature of the genetic code — not of the amino acids themselves.

Substitution — Worked Example

The diagram below shows mutations to the coding (sense) strand. The middle codon (AAT) is mutated in three different ways to show all three possible outcomes.

Base Deletion & Frameshift

In a base deletion, one base is removed from the DNA sequence. Because the genetic code is non-overlapping and read in triplets, this shifts every subsequent triplet — a frameshift mutation.

Frameshift

A mutation (deletion or insertion) that alters the reading frame of all codons downstream of the mutation site, producing a completely different — and usually non-functional — polypeptide.

Key Comparison

Substitution: affects one codon only. Deletion/insertion: causes a frameshift — every codon downstream is altered. This is why deletions and insertions are usually far more damaging.

Mutagenic Agents

Mutagenic Agent

A physical or chemical agent that increases the rate of mutation.

TypeExampleMechanism

Ionising radiationX-rays, gamma rays, alpha particlesBreaks DNA strands; causes base changes

UV radiationUV light (from sun)Causes adjacent thymine bases to bond together (thymine dimers), leading to mispairing during replication

Chemical mutagensSome industrial chemicals, components of tobacco smokeAlter base structure or substitute incorrect bases into DNA during replication

Spontaneous mutations also occur

Mutations arise spontaneously during DNA replication — even without a mutagenic agent — due to errors in base pairing that are not corrected by proofreading mechanisms. Mutagenic agents increase the rate of these errors; they do not create an entirely new class of mutation.

Spec Boundary

AQA spec 3.4.3 requires you to know that mutagenic agents increase the rate of mutation and to give examples. You are not required to memorise the precise molecular mechanism (e.g. thymine dimer formation) — but it may appear in context in a data question.

Chromosome Non-Disjunction

The failure of homologous chromosomes (in meiosis I) or chromatids (in meiosis II) to separate correctly during meiosis, resulting in daughter cells with an abnormal number of chromosomes.

Non-disjunction in Meiosis I

A pair of homologous chromosomes fails to separate at meiosis I. Both chromosomes move to the same pole. Two of the resulting cells have n+1 chromosomes; two have n−1 chromosomes.

Non-disjunction in Meiosis II

A pair of chromatids fails to separate at meiosis II. Both chromatids move to the same pole. One cell has n+1, one has n−1, and two are normal (n).

Critical Distinction — 2024 Examiner Report

The 2024 AQA examiner report noted that many students described homologous chromosomes failing to separate even when the question stated the non-disjunction occurred in meiosis II. In meiosis II, it is chromatids that should separate — not homologous chromosomes. Always re-read the question and specify the correct structures for the relevant division.

Non-Disjunction — Diagram

Trisomy 21 — Down Syndrome

Down syndrome is the most commonly examined example of chromosome non-disjunction in AQA biology.

FeatureDetail

CauseNon-disjunction of chromosome 21 during meiosis → gamete with 2 copies of chromosome 21 → fertilisation with normal gamete → zygote has 3 copies

Chromosome number47 chromosomes (2n + 1 = trisomy 21)

Division affectedMost commonly meiosis I (failure of homologous chromosomes to separate); can also occur in meiosis II (failure of chromatids to separate)

Genetic termTrisomy 21 — having three copies of chromosome 21

Exam phrasing — be precise

For meiosis I: "homologous chromosomes fail to separate" → gamete has n+1

For meiosis II: "chromatids fail to separate" → gamete has n+1

After fertilisation with a normal gamete: trisomy (2n+1 = 47)

Never say "the chromosomes don't split" — be specific about which structures and which division

Substitution vs Deletion — Comparison

FeatureBase SubstitutionBase Deletion

What changesOne base replaced by anotherOne base removed entirely

Codons affectedOnly the codon containing the substituted baseALL codons downstream of the deletion

Type of mutationPoint mutationFrameshift mutation

Possible outcomesSilent / missense / nonsenseUsually produces a very different, non-functional polypeptide; may create a premature stop codon

SeverityVariable — may have no effect (silent) or be catastrophic (nonsense)Usually highly damaging — whole protein changed from mutation point

Why?Genetic code is degenerate — not all base changes alter amino acidNon-overlapping code means every triplet after the deletion is shifted

Exam Tip

When comparing mutation types, always link your answer to properties of the genetic code: degeneracy explains why substitutions can be silent; non-overlapping explains why deletions cause frameshifts. These are the specification-level explanations AQA rewards.

Working Through Mutation Questions

AQA regularly gives a DNA or mRNA sequence and asks you to identify the type of mutation and predict the effect. Always work step-by-step.

Step-by-step approach

Identify the change: is a base replaced (substitution) or removed/added (deletion/insertion)?

Write out the mRNA codons before and after the mutation

If substitution: has the codon changed? Does it still code for the same amino acid?

State the type: silent / missense / nonsense (substitution) OR frameshift (deletion/insertion)

Predict the effect on the polypeptide and protein function

2024 Examiner Report — Critical Point

The 2024 AQA report found that many students saw a substitution mutation and immediately wrote lengthy accounts of how the protein would be non-functional — without first checking whether the substitution was silent. Always apply the degenerate code to the specific mutation given before predicting an effect. In 2024, the example was a synonymous substitution — students who assumed the protein changed scored zero for that part.

Precise language

Say: base sequences "code for" amino acids. The 2024 report also flagged that students lost marks for saying base sequences "produce" amino acids — this is incorrect. Sequences code for amino acids; ribosomes and tRNA produce polypeptides.

DEEP Framework: Mutation Effects

Use for "explain how a base deletion affects the polypeptide produced" — a common 4–5 mark question.

DEEP CHAIN — "Explain why a base deletion is more likely to produce a non-functional protein than a base substitution"

D

Define A base deletion removes one base from the DNA sequence. A base substitution replaces one base with another. A deletion causes a frameshift; a substitution does not.

E

Explain Mechanism Because the genetic code is non-overlapping, each base is read as part of exactly one triplet. Removing one base shifts the reading frame for all downstream triplets — every codon from the deletion onwards is altered, producing a completely different sequence of amino acids throughout the rest of the polypeptide. A substitution only affects one codon.

E

Evidence / Contrast A substitution may be silent — because the genetic code is degenerate, many alternative codons still code for the same amino acid (e.g. CCU and CCC both code for proline). So the polypeptide may be unchanged. After a deletion, however, the tertiary structure is almost certainly altered, so the active site or binding site is disrupted and the protein loses its specific function.

P

Practical / Prediction If a base deletion produces a premature stop codon downstream, translation terminates early, producing a truncated polypeptide that is likely non-functional. This is why frameshift mutations are associated with severe inherited conditions, while many substitution mutations are benign (silent).

Common Exam Errors

Error 1 — Assuming all substitutions change the protein

A base substitution may be silent if the new codon codes for the same amino acid (degenerate genetic code). Always check the specific codons given before predicting an effect. The 2024 AQA examiner report explicitly flagged this.

Error 2 — "Degenerate code of amino acids"

Say "the genetic code is degenerate" — not "the code of amino acids is degenerate." The 2024 report noted this phrasing lost marks. The property belongs to the genetic code, not to the amino acids themselves.

Error 3 — Confusing meiosis I and II in non-disjunction

If the question says non-disjunction occurs in meiosis I, write: "homologous chromosomes fail to separate." If it occurs in meiosis II, write: "chromatids fail to separate." The 2024 report found students wrote about homologous chromosomes even when told the event was in meiosis II — this scored zero.

Error 4 — "Base sequences produce amino acids"

DNA base sequences code for amino acids — they do not produce them. The ribosome and tRNA produce polypeptides. The 2024 examiner report flagged "produced" as non-creditworthy; use "code for" or "specify."

Practice Question

The diagram below shows part of a DNA coding strand before and after a mutation.

Original: 5'–ATG–CCT–GAA–TGG–3'

Mutant: 5'–ATG–CCT–CAA–TGG–3'

(a) Identify the type of mutation that has occurred. [1 mark]

(b) Using the codon table provided, the codons GAA and CAA code for glutamic acid and glutamine respectively. Identify the type of substitution and predict its effect on the polypeptide. [3 marks]

(c) If instead the mutation had been a deletion of the first base of the third codon (G), explain how the effect on the polypeptide would differ. [3 marks]

a)

Base substitution — one base has been replaced by another (G replaced by C at the first position of the third codon).

b)

This is a missense substitution — the codon has changed from GAA (glutamic acid) to CAA (glutamine). A different amino acid is incorporated at position 3, so the primary structure of the polypeptide is changed. This may alter the tertiary structure (3D shape), potentially making the protein non-functional. However, only this one amino acid is changed — the rest of the polypeptide sequence is unaffected.

c)

A deletion of the G at the start of codon 3 would cause a frameshift. Because the genetic code is non-overlapping, every codon downstream of the deletion would be shifted, producing a completely different amino acid sequence from position 3 onwards. The resulting polypeptide would have a very different primary structure, its tertiary structure would be altered, and the protein would almost certainly be non-functional. This is a far more severe effect than the missense substitution in part (b).

Synoptic Links

Mutations underpin many other areas of the specification. Paper 3 essays frequently ask students to link mutations to evolution, cancer, and protein function.

→ Topic 4.01 (Genetic Code)

The degenerate and non-overlapping properties of the genetic code directly determine whether a substitution is silent and why deletions cause frameshifts. These properties must be cited in mutation answers.

→ Topic 4.02 (Protein Synthesis)

Mutations in DNA alter the mRNA codon sequence, which alters the amino acids incorporated during translation. The primary sequence change leads to altered tertiary structure and loss of function.

→ Topic 2.04 (Cell Cycle)

Mutations in genes controlling the cell cycle can lead to uncontrolled cell division — cancer. This is the link between mutagenic agents (e.g. carcinogens in tobacco smoke) and tumour formation.

→ Topic 7.01 (Evolution)

Gene mutations provide the raw material for evolution. Beneficial mutations increase survival and reproductive success → selection → accumulation of favourable alleles in the population. Most mutations are neutral or harmful.

Summary

Key Definitions

TermDefinition

Gene mutationA change in the base sequence of DNA

Base substitutionA mutation in which one base is replaced by another; affects only one codon; may be silent, missense or nonsense

Base deletionA mutation in which one base is removed; causes a frameshift — all downstream codons are altered

Mutagenic agentA physical or chemical agent that increases the rate of mutation (e.g. ionising radiation, UV light, chemical mutagens)

Non-disjunctionFailure of homologous chromosomes (meiosis I) or chromatids (meiosis II) to separate; produces gametes with n+1 or n−1 chromosomes

Trisomy 21Down syndrome; caused by non-disjunction of chromosome 21 → gamete with extra chromosome 21 → zygote with 47 chromosomes

Substitution outcomes

Silent — same AA (degenerate code)

Missense — different AA

Nonsense — premature stop codon → truncated protein

Must-say phrases

"The genetic code is degenerate" (not "amino acids")

Base sequences "code for" amino acids (not "produce")

Meiosis I → homologous chromosomes fail to separate

Meiosis II → chromatids fail to separate