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This lesson covers the different types of gene mutation and their effects on protein structure and function, as required by the Edexcel A-Level Biology specification (9BI0, Topic 8). Understanding mutations is fundamental to explaining the origins of genetic variation.
A gene mutation (or point mutation) is a change in the nucleotide base sequence of DNA. Mutations can occur spontaneously during DNA replication or can be induced by mutagens (agents that increase the rate of mutation).
Mutations are the ultimate source of all genetic variation — without mutation, there would be no new alleles and no evolution.
| Mutagen type | Examples | Mechanism |
|---|---|---|
| Chemical | Nitrous acid, benzopyrene (in tobacco smoke), ethidium bromide | May alter bases, cause base analogues to be incorporated, or intercalate between bases |
| Radiation (ionising) | X-rays, gamma rays, UV light | Cause base modifications, thymine dimers (UV), or strand breaks |
| Biological | Certain viruses, transposons | Insert DNA sequences into genes |
Exam Tip: Mutations can occur spontaneously (without a mutagen) because DNA polymerase occasionally makes errors during replication. The error rate is approximately 1 in 10⁹ bases per replication in humans, thanks to proofreading mechanisms.
A substitution (point mutation) involves the replacement of one nucleotide base with another. There are three possible consequences:
| Type | Effect | Example |
|---|---|---|
| Silent (synonymous) | No change in amino acid — the new codon codes for the same amino acid due to the degeneracy of the genetic code | Third-position changes (wobble position) often have no effect |
| Missense | A different amino acid is incorporated — may or may not affect protein function | Sickle cell anaemia: GAG → GUG changes glutamic acid to valine in the beta-globin gene |
| Nonsense | The new codon is a premature stop codon — the polypeptide is truncated (shortened) | CAG (glutamine) → UAG (stop) |
Sickle cell anaemia is caused by a single base substitution in the HBB gene (chromosome 11):
| Normal | Mutant |
|---|---|
| DNA: CTC | DNA: CAC |
| mRNA: GAG | mRNA: GUG |
| Amino acid: Glutamic acid (position 6) | Amino acid: Valine (position 6) |
This single amino acid change (Glu → Val) causes the haemoglobin molecules to polymerise under low oxygen conditions, distorting red blood cells into a sickle shape. This leads to:
Exam Tip: Sickle cell anaemia is the most commonly examined example of a gene mutation. Make sure you can trace the effect from DNA change → mRNA change → amino acid change → protein change → phenotypic effect.
An insertion involves the addition of one or more extra nucleotides into the DNA sequence.
If the number of inserted bases is not a multiple of three, it causes a frameshift — every codon after the insertion is read differently. This usually results in a completely different amino acid sequence and a non-functional protein.
Example: Original sequence: AUG | GCA | UUC | GAA ...
If a single base (U) is inserted after the first codon:
AUG | UGC | AUU | CGA | A...
Every codon after the insertion is altered — this is a frameshift mutation.
A deletion involves the removal of one or more nucleotides from the DNA sequence.
Like insertions, deletions of non-multiples of three cause a frameshift. The consequences are usually severe because every amino acid downstream of the deletion is changed.
Cystic fibrosis — the most common mutation (ΔF508) involves a deletion of three nucleotides that code for phenylalanine at position 508 of the CFTR protein. Because three bases are deleted, the reading frame is maintained (no frameshift), but the loss of this amino acid causes the protein to misfold and be degraded.
An inversion involves a segment of DNA being reversed (flipped 180°). This can disrupt the reading frame if it occurs within a gene, or it may have no effect if it occurs in a non-coding region.
A duplication involves a segment of DNA being copied and inserted, producing a repeated sequence. Gene duplication is an important source of evolutionary novelty — the duplicate copy can accumulate mutations and potentially evolve a new function.
| Mutation type | Reading frame | Likely effect on protein |
|---|---|---|
| Silent substitution | Maintained | No change |
| Missense substitution | Maintained | One amino acid changed — may or may not affect function |
| Nonsense substitution | Maintained | Premature stop codon — truncated, non-functional protein |
| Insertion (not multiple of 3) | Shifted (frameshift) | Completely altered amino acid sequence — usually non-functional |
| Deletion (not multiple of 3) | Shifted (frameshift) | Completely altered amino acid sequence — usually non-functional |
| Insertion/deletion (multiple of 3) | Maintained | Amino acid(s) added/removed — may or may not affect function |
The following diagram summarises the types of point mutation and their consequences:
flowchart TD
A["Point Mutation"] --> B["Substitution"]
A --> C["Insertion"]
A --> D["Deletion"]
B --> E["Silent<br/>(same amino acid)"]
B --> F["Missense<br/>(different amino acid)"]
B --> G["Nonsense<br/>(premature stop codon)"]
C --> H["Frameshift<br/>(all downstream<br/>codons altered)"]
D --> H
Not all mutations have phenotypic consequences:
Exam Tip: Only mutations in gametes (or cells that give rise to gametes) are passed to the next generation. Somatic mutations can contribute to cancer but are not inherited.
Mutations are the raw material for evolution:
Without mutation, there would be no genetic variation and no evolution by natural selection.
| Concept | Key Detail |
|---|---|
| Substitution | One base replaced — silent, missense or nonsense |
| Insertion/Deletion | Bases added/removed — often causes frameshift |
| Frameshift | Reading frame altered — usually produces non-functional protein |
| Sickle cell | Single base substitution (Glu → Val) in HBB gene |
| Cystic fibrosis (ΔF508) | Three-base deletion — no frameshift but protein misfolds |
| Mutagens | Chemicals, radiation, biological agents increase mutation rate |
| Somatic vs germ line | Only germ line mutations are heritable |
Exam Tip: When asked about the effect of a mutation, always trace the pathway: DNA change → mRNA change → amino acid change → protein structure change → phenotypic effect. This systematic approach will score highly.