Explain how errors in DNA replication can lead to frameshift mutations and outline why frameshift mutations are often more damaging to protein function than missense mutations.

IB DP Biology Higher Level (2023 syllabus) — D1.3 Mutations and gene editing (HL only) · Explain · 4 marks · View as Markdown

Written & reviewed by James Millett — Biology (Imperial College London), PGCE Science (University of Cambridge).

Model answer (4 marks)

Frameshift mutations arise when nucleotide insertions or deletions that are not multiples of three occur during DNA replication, shifting the reading frame of codons downstream of the mutation.

Replication errors such as DNA polymerase slippage on repetitive sequences (e.g. microsatellites) can cause the polymerase to skip or duplicate nucleotides, introducing these indels.

A frameshift alters every codon from the point of the mutation to the stop codon, producing a completely different (and usually non‑functional) amino‑acid sequence in that region.

In contrast, a missense mutation changes only a single amino acid; the remainder of the primary sequence remains unchanged, so the protein may retain partial or full function. Thus, frameshifts are typically far more disruptive to protein structure and function.

Examiner tips

  • Use the exact phrase "frameshift mutations arise when…" to match the mark scheme.
  • Explain the mechanism (slippage) and the effect (altered codons to stop codon).
  • Contrast with missense by noting only one amino acid changes and the rest of the sequence is intact.
  • Keep answer concise – 4 points, no extra words.

Common mistakes

  • Confusing frameshift with point mutations or missense; not mentioning the 3‑nucleotide rule.
  • Failing to explain the slippage mechanism or the downstream effect on the entire protein.
  • Using vague terms like "major change" instead of specifying loss of function.

Mark scheme (4 marks)

  1. Frameshift mutations arise when nucleotide insertions or deletions (indels) that are not multiples of three occur during replication, shifting the reading frame of codons downstream of the mutation.
  2. Replication errors such as slippage of DNA polymerase on repetitive sequences (e.g. microsatellites) can cause the polymerase to skip or duplicate nucleotides, introducing these indels.
  3. A frameshift alters every codon from the point of the mutation to the stop codon, producing a completely different (and usually non-functional) amino acid sequence in that region.
  4. A missense mutation changes only a single amino acid, so the remainder of the primary sequence is unaffected and the protein may retain partial or full function; frameshifts are therefore typically far more disruptive to protein structure and function.

Key terms in this question

frameshift mutation · missense mutation

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