Lesson 3 of 9 / Mutation, cell division and cancer
From one substitution to sickling
How can one changed amino acid affect a whole cell?
In this lesson: Explain how a gene mutation can cause disease using sickle cell anaemia.
About 5 min
The key ideaA substitution in the beta-globin gene changes an amino acid, altering haemoglobin interactions and potentially red-cell shape and survival.
Explore the idea
Keep the sequence; change oxygen conditions
The genotype is not changing with oxygen. Oxygen conditions affect the behaviour of the altered haemoglobin; this is an illustrative cell, not a clinical prediction.
Explanation
The sickle-cell allele changes the beta-globin sequence so that valine replaces glutamic acid at a particular position. In a coding-strand example, GAG becomes GTG; the corresponding mRNA codon changes from GAG to GUG. This is a base substitution, not a frameshift.
Valine is hydrophobic whereas glutamic acid is charged under normal cellular conditions. This changes the surface properties of the haemoglobin subunit. Under low-oxygen conditions, haemoglobin S molecules can associate into fibres, making affected red cells less flexible and sickle-shaped.
Less flexible cells can obstruct small vessels, reducing blood delivery. Affected red cells are also broken down more rapidly, contributing to anaemia. The disease therefore reflects a chain of effects from DNA through protein interaction to cell behaviour and tissue function.
An allele's effect depends on genotype and conditions. The homozygous sickle-cell genotype has different consequences from the usual heterozygous trait. Do not infer that one changed base always causes the same disease or that every mutation has a major effect.
Step by step
- 1
DNA to amino acid
A codon change replaces glutamic acid with valine in beta-globin.
- 2
Amino acid to interaction
Altered surface properties promote haemoglobin aggregation under suitable conditions.
- 3
Cell to organism
Reduced flexibility, blockage and shortened cell survival affect blood function.
Worked example
Improve an incomplete answer
A student writes, "The mutation changes red-cell shape." Add the missing molecular steps.
One way to explain it
The substitution changes the beta-globin amino-acid sequence, replacing glutamic acid with valine. Altered surface properties allow haemoglobin S to form fibres under low oxygen, which distort the red cell and reduce flexibility.
Why this answer works
- Name the protein intermediate.
- Explain how a chemical change affects molecular association.
- Then connect the association to the cell.
Is this true? "The sickle-cell substitution shifts every later codon."
A substitution changes a base without adding or removing one, so the reading frame remains. The important effect is the changed amino acid and protein interaction.