How is 3.8 weighted and where does it appear in the AQA A-Level Biology exams?

3.8 is a Paper 2 topic (the second year content), but synoptic questions on Paper 3 frequently draw on it, especially recombinant DNA technology, PCR and genetic fingerprinting. Expect several multiple-choice marks, a structured question on gene regulation or cancer, and an applied data or method question on a technique such as PCR, electrophoresis or DNA probes. It is one of the most application-heavy topics in the specification, so practising unfamiliar-context questions matters more than rote recall.

What is the difference between a mutation and an epigenetic change?

A mutation changes the actual base sequence of the DNA. An epigenetic change does not touch the base sequence; it adds or removes chemical tags (methyl groups on DNA, acetyl groups on histones) that change whether a gene is transcribed. Both can be inherited and both can cause disease, but only a mutation alters the genetic code itself. Examiners love this contrast, so be able to state it in one sentence.

Do oncogenes and tumour suppressor genes work in the same way?

No, and reversing them is a classic error. A proto-oncogene normally stimulates the cell cycle; when it mutates into an oncogene it becomes over-active, so cell division is over-stimulated (increased expression). A tumour suppressor gene normally slows division or triggers apoptosis; cancer arises when it is switched off or inactivated (decreased expression). Increased activity of one and loss of activity of the other both lead to uncontrolled division.

What is the difference between in vivo and in vitro gene cloning?

In vivo cloning amplifies DNA inside living cells using a vector such as a plasmid; the gene is inserted into a host (e.g. bacteria) which copies it as it divides, and it can also express the protein. In vitro cloning is the polymerase chain reaction (PCR), which copies DNA in a test tube with no cells, using primers, free nucleotides and heat-stable Taq polymerase through cycles of denaturation, annealing and extension. PCR is faster and ideal for making many copies for analysis; in vivo cloning is used when you also want the protein product.

Why does genetic fingerprinting use VNTRs rather than genes?

Genetic fingerprinting compares variable number tandem repeats (VNTRs), which are non-coding sequences repeated a variable number of times. Because the number of repeats differs widely between individuals, the fragment lengths are almost unique to each person. Genes, by contrast, are very similar between people (they must code for working proteins), so they could not distinguish individuals. The VNTR fragments are cut out, separated by size on a gel and visualised as a banding pattern.

What is the single biggest scoring habit in 3.8?

Name the mechanism precisely and in the right order. Markers reward chains of reasoning: oestrogen is lipid-soluble, so it diffuses in, binds a receptor on a transcription factor, changes its shape, enters the nucleus, binds DNA, stimulates RNA polymerase. The same applies to PCR stages, electrophoresis and probe hybridisation. Vague answers ("it switches the gene on") cap your mark; ordered, named steps earn it.

EnglandBiology

AQA A-Level Biology 3.8 The control of gene expression: a full deep-dive on mutations, gene regulation, epigenetics, cancer and genetic technology

A deep-dive guide to AQA A-Level Biology 3.8, The control of gene expression. Connects gene mutations, transcription factors and siRNA, epigenetics, the genetics of cancer, recombinant DNA technology and gene probes, sequencing and genetic fingerprinting into one exam-ready story, with the question patterns AQA repeats.

Generated by Claude Opus 4.822 min readAQA-7402-3.8Updated 2026-06-02

Reviewed by: AI editorial process; not yet individually human-reviewed

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What 3.8 actually demands
The big idea: same genome, different cells
Mutations: changing the code itself
Regulating transcription and translation
Epigenetics: control without changing the code
The genetics of cancer
Reading, copying and moving genes
Finding genes and people: probes, sequencing and fingerprinting
How 3.8 is examined
Check your knowledge

What 3.8 actually demands

The control of gene expression is the topic where the whole of AQA A-Level Biology comes together. It assumes you already understand DNA structure, transcription and translation (3.4), and it then asks a deceptively simple question: if every cell in your body contains the same genes, why are your cells so different, and what happens when this control breaks down? The answer runs from molecular tags on DNA, through the genetics of cancer, to the laboratory techniques that let us read, copy and move genes.

Two skills are tested in roughly equal measure. The first is precise recall of named mechanisms in the correct order. The second, weighted heavily in Papers 2 and 3, is applying those mechanisms to unfamiliar data and contexts. Strong students learn the mechanisms as ordered chains, then practise bending them to new scenarios.

The big idea: same genome, different cells

A specialised cell expresses only some of its genes. Differentiation is the result of switching genes on and off, not of losing genes. This control happens at several stages:

Transcription can be switched on or off by transcription factors, and silenced epigenetically.
Translation can be blocked by RNA interference using siRNA.

Keeping this map in mind tells you where each mechanism in 3.8 acts.

Mutations: changing the code itself

A gene mutation changes the base sequence of DNA, usually as a random error during replication. The six named types are substitution, deletion, addition, inversion, duplication and translocation.

The two highest-value ideas are:

Substitutions affect only one triplet and may be silent because the code is degenerate (more than one triplet codes for the same amino acid). They can also be missense (one amino acid changed) or nonsense (a premature stop codon).
Deletions and additions cause a frameshift, so every triplet after the mutation is read differently. This is why their position matters: a frameshift near the start of a gene disrupts almost the whole polypeptide.

Mutagenic agents (ionising radiation, UV, certain chemicals) increase the mutation rate. A mutation in a gamete can be inherited; a mutation in a body cell affects only that cell's descendants, and may contribute to cancer.

Cell specialisation links here through stem cells: unspecialised cells that self-renew and differentiate. Learn the four potencies precisely: totipotent (any cell type including extra-embryonic tissue), pluripotent (any body cell type), multipotent (a limited range) and unipotent (one type). Induced pluripotent stem cells (iPS cells) are adult cells reprogrammed back to pluripotency by switching on specific transcription-factor genes, sidestepping the ethics of embryonic stem cells.

Regulating transcription and translation

Transcription is controlled by transcription factors: proteins that move from the cytoplasm into the nucleus and bind specific DNA sequences to stimulate or inhibit RNA polymerase.

The set-piece example is oestrogen:

Oestrogen is lipid-soluble, so it diffuses through the cell-surface membrane.
It binds a receptor on a transcription factor, changing its shape so it becomes complementary to a DNA sequence.
The oestrogen-receptor complex enters the nucleus, binds DNA and stimulates RNA polymerase, increasing transcription of the target gene.

This is also the mechanism that links oestrogen to breast cancer: in oestrogen-receptor-positive tumours, oestrogen drives the division of already abnormal cells.

Translation is controlled by RNA interference. A double-stranded RNA is cut into short siRNA fragments; one strand, complementary to a target mRNA, binds it and guides proteins that cut the mRNA (or simply block it), so the polypeptide is not made. Transcription factors decide whether mRNA is made; siRNA decides whether existing mRNA is translated.

Epigenetics: control without changing the code

Epigenetics is a heritable change in gene expression without a change to the DNA base sequence. The two named mechanisms both inhibit transcription:

Increased methylation of DNA. Methyl groups added to the promoter stop transcription factors binding, so the gene is not transcribed.
Decreased acetylation of histones. Removing acetyl groups increases the positive charge on histones, so they bind the negatively charged DNA more tightly; the DNA condenses and RNA polymerase cannot reach the gene.

Because these tags can be copied during cell division (and sometimes passed to offspring), they are heritable. Because they do not change the base sequence, they are potentially reversible, which makes them drug targets. Environmental factors such as diet and toxins can alter the pattern, and abnormal patterns contribute to disease, especially cancer.

The genetics of cancer

Cancer is uncontrolled cell division caused by changes in gene expression. Two gene groups dominate:

Oncogenes are mutated proto-oncogenes that are over-active and continuously stimulate division (increased expression).
Tumour suppressor genes normally slow the cycle or trigger apoptosis; when inactivated they remove the brakes (decreased expression).

Abnormal methylation ties cancer back to epigenetics: hypermethylation silences a tumour suppressor gene, while hypomethylation can activate an oncogene. Increased oestrogen exposure raises the risk of some breast cancers by stimulating the division of breast cells. Finally, distinguish benign tumours (slow, localised, encapsulated) from malignant tumours (faster, invasive, metastasising, de-differentiated).

Reading, copying and moving genes

Recombinant DNA technology transfers a DNA fragment between organisms. It works because the genetic code is universal, so a transferred gene is transcribed and translated correctly in the recipient.

Isolating the gene: Three methods: reverse transcriptase (mRNA to intron-free cDNA), restriction endonucleases (cutting at specific recognition sites, often leaving sticky ends), and the gene machine (synthesising the sequence chemically).
Amplifying the DNA: In vivo, the gene is inserted into a vector (plasmid) cut with the same restriction enzyme, joined by DNA ligase, and taken up by host cells in transformation; marker genes identify which cells took up the plasmid. In vitro, PCR copies DNA in cycles of denaturation (95 degrees C), annealing of primers (about 55 degrees C) and extension by Taq polymerase (72 degrees C), doubling the DNA each cycle ( $2^n$ after $n$ cycles).
Using transformed organisms: Bacteria transformed with the human insulin gene make insulin; GM crops gain useful traits. Gene therapy supplies a working allele via a vector to treat genetic disease; somatic therapy treats body cells (often temporarily) and germ-line therapy would be inherited but is ethically restricted.

Finding genes and people: probes, sequencing and fingerprinting

Labelled DNA probes are short single-stranded DNA complementary to a target, carrying a radioactive or fluorescent label. They hybridise to the target by complementary base pairing, and the label reveals whether a specific allele is present, the basis of much medical diagnosis and personalised medicine.

DNA sequencing reads the base order; high-throughput (next-generation) sequencing made this fast and cheap, supporting genome projects and tailored treatment.

Genetic fingerprinting uses VNTRs (variable number tandem repeats) whose repeat number varies between individuals. The DNA is cut, separated by size using gel electrophoresis (smaller fragments travel further toward the positive electrode), and visualised as a banding pattern. Uses include paternity and relationship testing, forensic identification, and measuring genetic variability in populations.

How 3.8 is examined

A typical exam profile:

Multiple choice. Recall of mutation types, transcription factor action, methylation versus acetylation, oncogene versus tumour suppressor.
Structured questions. Explain oestrogen action, explain how a named mutation or methylation event leads to cancer, describe a technique step by step.
Applied and synoptic. Interpret electrophoresis gels, calculate PCR yields, evaluate gene therapy or GM ethics, read unfamiliar data on gene regulation.

Check your knowledge

A mix of recall, mechanism and applied questions. Answer under exam conditions, then check against the solutions block.

Explain why a substitution mutation may have no effect on the polypeptide a gene codes for, but a deletion of one base usually does. (4 marks)
Describe how oestrogen increases the transcription of a target gene, naming each step in order. (4 marks)
(a, 2) Explain how increased methylation of DNA inhibits transcription. (b, 2) Explain how decreased acetylation of histones inhibits transcription. (4 marks)
A tumour is oestrogen-receptor positive and one of its tumour suppressor genes is hypermethylated. Explain how each factor contributes to uncontrolled cell division. (4 marks)
A gene is to be inserted into a bacterial plasmid. (a, 2) Explain why the gene and plasmid are cut with the same restriction endonuclease. (b, 2) Explain the role of DNA ligase and of a marker gene. (4 marks)
PCR is carried out for 12 cycles starting from 50 copies of a DNA fragment. (a, 1) Calculate the number of copies produced. (b, 3) Describe the three temperature stages of one PCR cycle and what happens at each. (4 marks)
Explain how a labelled DNA probe can be used to diagnose whether a patient carries a disease-causing allele. (3 marks)
Describe how a genetic fingerprint is produced from a blood sample and used to confirm a family relationship. (5 marks)

Solutions

Q1: A substitution changes only one base and therefore only one triplet. Because the genetic code is degenerate, more than one triplet codes for the same amino acid, so the new triplet may still code for the same amino acid (a silent mutation), leaving the amino acid sequence and so the polypeptide unchanged. A deletion of one base shifts the reading frame (a frameshift): every triplet after the deletion is read differently, so many amino acids downstream are changed and a premature stop codon may appear, producing a very different, usually non-functional polypeptide.
Q2: (i) Oestrogen is lipid-soluble, so it diffuses through the phospholipid cell-surface membrane into the cytoplasm. (ii) It binds to a receptor site on a transcription factor (the oestrogen receptor). (iii) Binding changes the shape of the receptor so it becomes complementary to a specific DNA sequence, activating the transcription factor. (iv) The oestrogen-receptor complex enters the nucleus, binds to the DNA near the target gene and stimulates RNA polymerase, so transcription increases and more mRNA (and protein) is made.
Q3: (a) Methyl groups added to the DNA (often in the promoter) prevent transcription factors and RNA polymerase from binding, so the gene is not transcribed and no mRNA is made. (b) Removing acetyl groups increases the positive charge on the histones, so they bind the negatively charged DNA more tightly; the DNA-histone complex becomes more condensed, transcription factors cannot bind, and transcription is inhibited.
Q4: Oestrogen binds the receptor on a transcription factor; the complex enters the nucleus and switches on genes that stimulate cell division, so abnormal cells divide more. Hypermethylation of the tumour suppressor gene's promoter prevents its transcription, so its protein (which normally slows the cycle or triggers apoptosis) is not made, removing control of cell division. Together they increase the rate of division, allowing a tumour to form.
Q5: (a) The same restriction endonuclease cuts at the same recognition sequence, producing complementary sticky ends on both the gene and the plasmid, so they can base-pair and join. (b) DNA ligase forms phosphodiester bonds to seal the gene into the plasmid, producing recombinant DNA. A marker gene (e.g. antibiotic resistance or fluorescence) allows bacteria that have taken up the plasmid to be identified and selected from those that have not.
Q6: (a) Each cycle doubles the DNA, so after 12 cycles: $50 \times 2^{12} = 50 \times 4096 = 204\,800$ copies. (b) Denaturation at about 95 degrees C breaks hydrogen bonds, separating the two strands. Annealing at about 55 degrees C lets primers bind to the start of each target strand by complementary base pairing. Extension at about 72 degrees C lets heat-stable Taq DNA polymerase build a new complementary strand from each primer using free nucleotides.
Q7: A single-stranded DNA probe with a base sequence complementary to the disease-causing allele is labelled (radioactively or fluorescently). The patient's DNA is made single-stranded and mixed with the probe; if the allele is present, the probe hybridises to it by complementary base pairing. The label is then detected (on film or under UV); a signal shows the patient carries the allele, confirming the diagnosis.
Q8: DNA is extracted from the blood sample (and amplified by PCR if needed). It is cut with restriction endonucleases at sites around the VNTRs, which vary in length between individuals. The fragments are separated by size using gel electrophoresis: the negatively charged DNA moves toward the positive electrode and smaller fragments travel further. The fragments are made single-stranded, transferred to a membrane and visualised with labelled probes to give a banding pattern. Each band in a child must come from one parent; comparing the patterns of the individuals shows whether the shared bands are consistent with the claimed relationship.