Causes and Consequences of Mutations Revision Notes | A Level AQA Biology

1. Why Mutations Matter: The Link Between DNA and Protein

Your DNA is a molecular instruction manual. Every gene is a sequence of bases that codes for a specific polypeptide — and that polypeptide's shape, and therefore its function, depends entirely on getting those bases in the right order.

Change even a single base in the wrong place, and you can alter an amino acid, distort the polypeptide's tertiary structure, and destroy its function. That is the core story of gene mutations — and it is exactly what AQA wants you to be able to explain with precision.

To understand mutations, you first need to hold two things in mind simultaneously: the DNA base sequence and the triplet codons it produces during transcription. A mutation at the DNA level ripples outward by changing the mRNA codons, which in turn alters which tRNA anticodon can base-pair with them—this determines which amino acid is incorporated. Every mutation type you will meet in this lesson disrupts that chain in a different way.

2. The Six Types of Gene Mutation

AQA specifies six distinct mutation types. Each one describes a different way the base sequence can be altered. Picture a short stretch of DNA with the sequence ATG-CGT-AAC as your reference point — you will see how each mutation type transforms it.

Substitution is the most common mutation type and, crucially, does not shift the reading frame. Because the genetic code is degenerate — most amino acids have more than one codon — a substitution sometimes produces a codon that still codes for the same amino acid. This is called a silent mutation. When the new codon codes for a different amino acid, it is a missense mutation. When it produces a stop codon prematurely, it is a nonsense mutation, which truncates the polypeptide.

Addition and deletion are the most disruptive mutation types because they cause a frameshift. The ribosome reads codons in non-overlapping triplets from a fixed start point. Insert one extra base and every triplet from that point onwards is read out of register — the entire downstream amino acid sequence changes. The polypeptide produced is almost always non-functional.

There is an important exception worth knowing: if three bases are deleted together as a complete codon (an in-frame deletion), the reading frame is restored after the deletion site. The polypeptide will be missing one amino acid at that position, but the rest of the sequence may be largely unaffected. However, a specific example like cystic fibrosis caused by the ΔF508 deletion (a three-base in-frame deletion) results in the CFTR protein being severely misfolded and degraded, so very little functional protein reaches the membrane. This illustrates that while the reading frame can be restored, protein function may still be dramatically affected depending on which amino acid is deleted and its importance for folding or function.

Inversion affects only the codons within the inverted segment. Bases outside the inverted region are unaffected. The number of bases in the gene stays the same, so there is no frameshift — but the codons within the inverted stretch are scrambled, and the amino acids they encode will change.

Duplication and translocation both alter gene dosage or gene context. A duplicated segment may produce excess protein product, while a translocated segment may be placed under the control of a different promoter, altering when and how much of the protein is made. Both can have significant consequences for cell function.

3. How Mutations Arise: Spontaneous Errors and Mutagenic Agents

Mutations do not require an external trigger. They occur spontaneously during DNA replication, when DNA polymerase occasionally incorporates the wrong complementary base. The enzyme has proofreading activity that corrects most errors, but a small number slip through — giving a background mutation rate that is low but never zero.

The spontaneous mutation rate can be significantly increased by mutagenic agents. These fall into two broad categories: physical mutagens and chemical mutagens. Physical mutagens include ionising radiation (such as X-rays and gamma rays) and ultraviolet radiation, which can cause adjacent thymine bases to form covalent bonds with each other — so-called thymine dimers — distorting the double helix and causing errors during replication. Chemical mutagens include base analogues that are incorporated into DNA in place of normal bases, and intercalating agents that insert between base pairs and cause addition or deletion errors during replication.

The key distinction AQA expects you to make is this: mutations occur spontaneously at a low background rate, and mutagenic agents increase that rate. Mutagenic agents do not create an entirely new category of mutation — they make the same types of error more frequent.

Mutations that arise in germline cells (cells that produce gametes) can be passed to offspring and may become heritable. Mutations in somatic cells (body cells) affect only the individual and cannot be inherited, but they can contribute to conditions such as cancer if they occur in genes controlling cell division.

4. From Mutation to Altered Polypeptide: Tracing the Consequences

Now that you know the mutation types and how they arise, the critical exam skill is tracing the consequence of a specific mutation through to the polypeptide. The pathway is always: altered DNA base sequence → altered mRNA codon sequence → altered tRNA anticodon matching → altered amino acid sequence → altered primary structure → potentially altered tertiary structure → altered (or lost) protein function.

Worked example: Tracing the Effect of a Substitution Mutation on a Polypeptide

A section of the template strand of DNA reads: 3'-TAC-GGG-AAT-5'. A substitution mutation changes the middle base of the second codon from G to A, giving: 3'-TAC-GAG-AAT-5'. Determine the effect on the polypeptide.

1. Template (3'→5'): TAC-GGG-AAT mRNA (5'→3'): AUG-CCC-UUA — mRNA is complementary and antiparallel to the template strand. T pairs with A, A pairs with U, G pairs with C, C pairs with G.
2. AUG = Methionine (start codon) CCC = Proline UUA = Leucine — Use the genetic code table to translate each codon. The polypeptide begins Met-Pro-Leu.
3. Mutated template (3'→5'): TAC-GAG-AAT mRNA (5'→3'): AUG-CUC-UUA — The middle base of the second codon changed from G to A on the template strand, so the mRNA codon changes from CCC to CUC.
4. CUC = Leucine — CCC (Proline) has been changed to CUC (Leucine). This is a missense mutation — a different amino acid is now incorporated at position 2.
5. Original: Met-Pro-Leu Mutated: Met-Leu-Leu — The primary structure has changed at position 2. If this position is critical for the protein's tertiary structure (e.g. within an active site or a region forming hydrogen bonds), the protein's shape and function may be altered or lost.

Answer: The substitution mutation changes codon 2 from CCC (Proline) to CUC (Leucine), altering the primary structure of the polypeptide at position 2. Whether this affects protein function depends on the significance of that position in the tertiary structure.

Notice the conditional language in the final answer above — 'whether this affects protein function depends on the significance of that position'. This is important. Not every amino acid change destroys protein function. If the substituted amino acid has similar chemical properties (e.g. both are non-polar), the tertiary structure may be largely preserved. AQA mark schemes reward this level of nuance.

Worked example: Tracing the Effect of an Addition Mutation (Frameshift)

A section of the coding strand of DNA reads: ATG-CGT-AAC. An extra base (T) is inserted after the first codon: ATG-TCG-TAA-C... Determine the consequence for the polypeptide.

1. Original coding strand: ATG-CGT-AAC mRNA: AUG-CGU-AAC Amino acids: Met-Arg-Asn — The coding strand has the same sequence as mRNA (with T replaced by U). Translate each codon using the genetic code.
2. Mutated coding strand: ATG-TCG-TAA-C... mRNA: AUG-UCG-UAA-... — Inserting T after position 3 shifts every subsequent base one position to the right. The ribosome still reads in triplets from the start, so all downstream codons are now different.
3. AUG = Met UCG = Serine UAA = Stop codon — The second codon has changed from CGU (Arg) to UCG (Ser), and the third codon has changed from AAC (Asn) to UAA — a premature stop codon.
4. Original polypeptide: Met-Arg-Asn-... Mutated polypeptide: Met-Ser (then translation terminates) — The frameshift has introduced a premature stop codon. The polypeptide is truncated after just two amino acids. This is almost certainly non-functional.

Answer: The addition of one base causes a frameshift, changing all downstream codons. In this example, a premature stop codon (UAA) is introduced at position 3, producing a severely truncated, non-functional polypeptide.

5. Silent, Missense, and Nonsense: Classifying Substitution Outcomes

Because substitution mutations are so common in exam questions, it is worth spending time on the three possible outcomes. The outcome depends entirely on which codon is produced by the substitution and what that codon codes for.

• Silent mutation: the new codon codes for the same amino acid as the original. The primary structure of the polypeptide is unchanged. This is possible because most amino acids are encoded by multiple codons (the degenerate code).
• Missense mutation: the new codon codes for a different amino acid. The primary structure changes at that position. Whether protein function is affected depends on the chemical properties of the new amino acid and its location in the polypeptide.
• Nonsense mutation: the new codon is a stop codon (UAA, UAG, or UGA). Translation terminates prematurely, producing a truncated polypeptide that is almost always non-functional.

Sickle cell anaemia is the classic exam example of a missense mutation. A single base substitution in the gene encoding the beta-globin chain of haemoglobin changes codon 6 from GAG (glutamic acid) to GUG (valine). Glutamic acid is hydrophilic; valine is hydrophobic. This single amino acid change causes the haemoglobin molecules to aggregate under low-oxygen conditions, distorting red blood cells into a sickle shape.

6. Exam Technique: Answering Mutation Questions for Full Marks

Mutation questions appear regularly in AQA papers and tend to follow predictable patterns. The most common formats are: identify the mutation type from a given base sequence change; explain the effect on the polypeptide; or evaluate why a particular mutation is more or less damaging than another. Each format rewards a different level of response.

When a question asks you to explain the effect of a mutation, the mark scheme almost always requires a chain of reasoning: state what changes in the base sequence → state how this changes the mRNA codon → state how this changes the amino acid → state the consequence for the polypeptide structure → state the consequence for protein function. Stopping at 'the amino acid changes' typically earns only partial credit.