explain that a gene mutation is a result of substitution or deletion or insertion of nucleotides in DNA and outline how each of these types of mutation may affect the polypeptide produced

Protein Synthesis – Gene Mutations (Cambridge 9700, Topic 6.2)

Learning objective

Explain that a gene mutation results from the substitution, deletion or insertion of nucleotides in DNA and outline how each type of mutation may affect the polypeptide produced.

1. What is a gene mutation?

  • Definition: a permanent change in the nucleotide sequence of a DNA segment that codes for a protein.

  • Mutations may arise spontaneously (replication errors) or be induced by mutagens such as UV light, chemicals or radiation.

  • The genetic code is read in triplets (codons); any change can alter the corresponding mRNA codon(s) and therefore the amino‑acid sequence of the polypeptide.

2. The universal genetic code and redundancy

  • Each codon (three nucleotides) specifies one of the 20 standard amino‑acids or a stop signal.

  • Because the code is redundant (several codons code for the same amino‑acid), some base changes do not change the amino‑acid – these are called silent mutations.

  • If the reading frame is disturbed (insertion or deletion not a multiple of three), the downstream codons are read incorrectly – a frameshift.

3. Types of nucleotide changes and their effect on the polypeptide

3.1 Substitution (point mutation)

  • Silent mutation – codon still encodes the same amino‑acid.

    Example: GAA → GAG (both code for Glutamate). Polypeptide unchanged.

  • Missense mutation – codon now encodes a different amino‑acid.

    Example: Sickle‑cell disease: GAG → GTG changes Glutamate → Valine at position 6 of β‑globin. May alter protein function.

  • Nonsense mutation – codon becomes a stop codon.

    Example: β‑thalassaemia: CAA → UAA creates a premature stop, truncating the β‑globin chain.

3.2 Deletion

  • In‑frame deletion (multiple of 3 nucleotides removed) – whole codon(s) are lost, reading frame unchanged.

    Example: Cystic fibrosis ΔF508 – loss of three nucleotides (phenylalanine) from the CFTR protein.

  • Frameshift deletion (not a multiple of 3) – reading frame shifts, altering every downstream codon and usually producing an early stop.

    Example: Duchenne muscular dystrophy – deletion of a single nucleotide in the dystrophin gene.

3.3 Insertion

  • In‑frame insertion (multiple of 3 nucleotides added) – adds extra codon(s) without changing the downstream frame.

    Example: Insertion of three nucleotides in the α‑globin gene adds an extra leucine.

  • Frameshift insertion (not a multiple of 3) – shifts the reading frame, altering downstream codons and often creating a premature stop.

    Example: Single‑base insertion in the BRCA1 gene.

4. Outline of how each mutation type affects the polypeptide

In summary:

  • Substitutions may be silent (no change), missense (single amino‑acid change) or nonsense (premature termination).

  • Deletions or insertions that are multiples of three remove or add whole codons, producing a slightly shorter or longer protein.

  • Deletions or insertions that are not multiples of three cause a frameshift, leading to a markedly altered amino‑acid sequence and usually a truncated, non‑functional protein.

5. Effect of each mutation type on the resulting polypeptide

Mutation typeDNA changeEffect on mRNA codonsResulting polypeptideTypical functional consequence
Silent substitutionSingle base replaced, codon still codes same AANo changeNormal length & sequenceUsually no effect on function
Missense substitutionSingle base replaced, codon codes different AAOne amino‑acid alteredFull‑length protein with one changed residueMay reduce, abolish, or occasionally enhance activity (e.g., sickle‑cell)
Nonsense substitutionSingle base replaced, creates stop codonPremature terminationTruncated proteinLoss‑of‑function (e.g., β‑thalassaemia)
Deletion – in‑frame (×3 nt)Whole codon(s) removedMissing amino‑acid(s)Shorter proteinMay affect stability or activity (e.g., CF ΔF508)
Deletion – frameshift (≠ multiple of 3)Base(s) removed, reading frame shiftsAll downstream codons altered; early stop often appearsHighly altered, usually truncated proteinSevere loss‑of‑function (e.g., Duchenne muscular dystrophy)
Insertion – in‑frame (×3 nt)Extra codon(s) addedAdditional amino‑acid(s)Longer proteinMay disturb folding or create new functional sites
Insertion – frameshift (≠ multiple of 3)Base(s) added, reading frame shiftsAll downstream codons altered; premature stop often followsAberrant, usually truncated proteinSevere loss‑of‑function (e.g., BRCA1 frameshift)

6. From gene to functional protein – key points

  • DNA mutation → altered mRNA codon(s) → changed amino‑acid sequence → possible alteration of protein folding, stability or activity.

  • Frameshift mutations generally have the most severe impact because they change every downstream amino‑acid and often introduce a premature stop.

  • A single amino‑acid substitution can be harmless or dramatically alter function if it occurs at an active or structural site.

7. Summary checklist for the exam

  1. Define a gene mutation as substitution, deletion or insertion of nucleotides in DNA.

  2. State that the genetic code is read in triplets and is redundant.

  3. Identify the three possible outcomes of a substitution (silent, missense, nonsense).

  4. Distinguish in‑frame vs. frameshift deletions and insertions.

  5. Explain how each type changes the polypeptide (no change, single‑AA change, truncated, longer, or severely altered).

  6. Recall one real‑world example for each category.

Suggested diagram: flow of genetic information (DNA → mRNA → polypeptide) with colour‑coded boxes showing where substitution, deletion and insertion mutations occur and how they alter the downstream protein.