Copying DNA is accurate but not perfect. A gene mutation changes the sequence of base pairs; whether the polypeptide changes, and how badly, depends on the kind of change and where it falls in the reading frame.
A gene mutation is a change in the sequence of base pairs in a DNA molecule that may result in an altered polypeptide. In a substitution one base pair is replaced by another, so only one codon changes: because the code is degenerate it may still code for the same amino acid (no effect), it may code for a different amino acid (as in sickle cell anaemia, where glutamic acid becomes valine in β-globin), or it may become a stop codon (a shortened polypeptide). A deletion or insertion of one nucleotide causes a frameshift: every codon after the mutation is read differently, so many amino acids change and a stop codon often appears early. The polypeptide usually folds wrongly and cannot function.
Fig. 1: the start of the β-globin mRNA after a substitution and after a deletion; only the deletion shifts the reading frame
Section 01
Substitution, deletion, insertion.
Start on normal, then click substitution, silent substitution, deletion and insertion in turn. The DNA coding strand of the start of the β-globin gene is on top, the polypeptide below; red spheres are amino acids that have changed.
Mutation in the lab
DNA change (coding strand)
Effect on the polypeptide
substitution
GAG becomes GTG in codon 7
glutamic acid replaced by valine; every other amino acid unchanged
silent substitution
GAG becomes GAA
still glutamic acid: no change, because the code is degenerate
deletion
one base removed from codon 4
frameshift: every amino acid from codon 4 onwards changes
insertion
one extra base added in codon 4
frameshift: amino acids change and a stop codon (TGA in DNA, UGA in mRNA) appears after only six amino acids
Gene mutation: a change in the sequence of base pairs in DNA. It may or may not alter the polypeptide.
Sickle cell anaemia: the single substitution in the β-globin gene puts valine, a non-polar amino acid, where glutamic acid (charged) should be. The haemoglobin molecules stick together at low oxygen concentration and distort red blood cells into sickle shapes. (In the finished chain this is amino acid 6, because the first methionine is removed.)
Examiner trap
Do not write that a mutation is a change in an amino acid or in a protein. A gene mutation is a change in the DNA base sequence; a changed polypeptide is a possible consequence.
Stage 1 · Learn
Check what the sim just showed you
Four quick checks. Each correct answer earns XP and records this skill on your profile.
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Choose substitution in the simulator. Which amino acid replaces glutamic acid?
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Why does the silent substitution show no red amino acids?
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After the deletion, why are all the amino acids from codon 4 onwards red?
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What happens to the polypeptide after the insertion in the simulator?
Section 02
Why some mutations matter more.
The same three types of change have very different effects depending on what they do to the codons. Work through the outcomes from mild to severe.
Substitution, same amino acid: the new codon codes for the same amino acid (often a change in the third base), so the polypeptide is unchanged.
Substitution, different amino acid: one amino acid differs. The effect depends on its R group and position: a change in an active site or in a part needed for folding can destroy function; a similar R group may have little effect.
Substitution, new stop codon: translation ends early, giving a shortened polypeptide that usually does not function.
Deletion or insertion of one nucleotide: shifts the reading frame from that point. Usually many amino acids change, the primary structure differs, and so the polypeptide folds into a different tertiary structure and is non-functional.
Position: a frameshift near the start of a gene changes almost the whole polypeptide; near the end, only the last few amino acids.
Three nucleotides: inserting or deleting three nucleotides adds or removes one amino acid without shifting the frame, usually a smaller effect.
Stage 2 · Exam
Exam-style questions
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Which statement best defines a gene mutation?
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A deletion of one base near the start of a gene usually has a greater effect than a substitution of one base. Why?
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A template-strand triplet changes from TTC to TTT, so the mRNA codon changes from AAG to AAA. Both code for lysine. What type of mutation is this, and what is its effect?
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Which change to a gene is least likely to alter the function of its polypeptide?
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Gene mutations, mastered.
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