Mutations that change protein structure

Molecules (Continuity and change) · Protein synthesis · note 4 of 8

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Mutations that change protein structureSpec D1.2.11

In short

A mutation that changes the base sequence of a gene can change the amino acid sequence of its polypeptide, and so the protein's structure. In sickle-cell anaemia, a base substitution in the haemoglobin beta-chain gene changes the codon GAG to GUG, so valine replaces glutamic acid. Haemoglobin S forms fibres at low oxygen, distorting red blood cells.

The amino acid sequence of a polypeptide decides how it folds and therefore its three-dimensional structure. A change in the base sequence of a gene can change the codons in the mRNA, and so the amino acid sequence, the folding and the function of the protein.

Example: sickle-cell anaemia

The gene for the beta chain of haemoglobin has a base substitution: on the coding strand, A is replaced by T (GAG becomes GTG).
The mRNA codon becomes GUG instead of GAG.
At the sixth amino acid of the beta chain, valine replaces glutamic acid. The resulting form is haemoglobin S.
Glutamic acid is charged and hydrophilic; valine is non-polar and hydrophobic. At low oxygen concentrations, haemoglobin S molecules stick together into long fibres.
The fibres distort red blood cells into a rigid sickle shape. Sickle cells can block capillaries and carry less oxygen, and they are broken down faster, causing anaemia.

A change to just one base of the gene is enough to alter the protein. This shows how closely protein structure depends on base sequence.

Codons 5 to 7 of the haemoglobin beta-chain gene: the normal allele reads CCT GAG GAG on the coding strand, CCU GAG GAG in mRNA, giving Pro Glu Glu; the mutant allele has GTG, mRNA GUG and valine at codon 6, with the changed base circled; below, a normal biconcave red blood cell beside a sickle cell containing haemoglobin S fibres. — Sickle-cell anaemia: one base substitution (GAG → GTG) changes glutamic acid to valine in haemoglobin.

Exam tip:

In a sickle-cell answer, give the base change, the codon change (GAG → GUG), the amino acid change (Glu → Val) and the effect on haemoglobin and red blood cells. Each is a separate marking point.

Written and checked against the IB Biology HL specification · Updated October 2026

Frequently asked questions

What is the difference between transcription and translation?

Transcription is the synthesis of RNA using a DNA template, carried out by RNA polymerase in the nucleus of eukaryotes. Translation is the synthesis of a polypeptide from mRNA at a ribosome, where tRNA anticodons pair with mRNA codons and amino acids are joined by peptide bonds. Transcription copies the sequence; translation decodes it.

Why is the genetic code a triplet code?

The genetic code is a triplet code because there are four bases and twenty amino acids. Pairs of bases would give only 4² = 16 combinations, too few for twenty amino acids. Triplets give 4³ = 64 codons, enough for every amino acid plus start and stop signals, which is why the code is also degenerate.

How does sickle-cell anaemia change the haemoglobin protein?

Sickle-cell anaemia is caused by a base substitution in the haemoglobin beta-chain gene. The mRNA codon changes from GAG to GUG, so valine replaces glutamic acid at the sixth amino acid. This hydrophobic valine makes haemoglobin S molecules stick together into fibres at low oxygen, distorting red blood cells into sickle shapes.

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