AQA A-level Biology: Regulation of Gene Expression and Cancer (7402) – Revision Notes

These are condensed revision notes for AQA A-level Biology (7402) sections 3.8.2.2, Regulation of transcription and translation, and 3.8.2.3, Gene expression and cancer, from the AQA AS and A-level Biology specification for first teaching 2015. Both sections are A-level only. For full explanations read the study guide, then test yourself with the practice questions. See also the AQA A-level Biology hub, the printable checklist and the free diagnostics.

Key definitions

Term	Meaning
Gene expression	Transcription of a gene and translation of its mRNA into a polypeptide
Transcription factor	A protein that attaches to one particular base sequence beside a gene and either switches on or blocks its transcription
Epigenetics	Heritable changes in gene function without changes to the base sequence of DNA
DNA methylation	Addition of methyl groups to DNA; increased methylation inhibits transcription
Histone acetylation	Addition of acetyl groups to histones; decreased acetylation inhibits transcription
RNA interference (RNAi)	Inhibition of translation of an mRNA by small RNA that pairs with it
Tumour	A mass of cells from uncontrolled division
Oncogene	Mutated or over-expressed form of a gene that stimulates division
Tumour suppressor gene	A gene that slows division, repairs DNA or triggers cell death
Metastasis	Spread of malignant cells to form secondary tumours elsewhere

Controlling transcription with oestrogen

Method in steps:

1. Oestrogen is a lipid-soluble steroid hormone. It diffuses through the cell-surface membrane.
2. It binds to a complementary receptor in the cytoplasm of target cells.
3. The receptor changes shape and the hormone-receptor complex acts as a transcription factor.
4. The complex moves through a nuclear pore into the nucleus.
5. It binds to a specific base sequence near the target gene.
6. RNA polymerase can bind, so the gene is transcribed and the protein is made.

Must-know point: a cell without the receptor does not respond, even though the hormone reaches it. The receptor is the reason for target-cell specificity.

Epigenetic control

	Increased methylation	Decreased acetylation
What is added or lost	Methyl groups added to DNA	Acetyl groups lost from histones
Result	DNA less accessible	Histones keep their positive charge and attract DNA phosphate groups strongly
DNA packing	Tighter	Tighter
Transcription	Inhibited	Inhibited
Base sequence	Unchanged	Unchanged

• The marks can be copied to daughter cells, so the pattern is heritable.
• Environmental change can alter the pattern, which is why identical twins can become different over time.
• Epigenetic change is not mutation: no base is substituted or deleted.
• Reversal of the marks, in principle, can switch genes back on, which is why epigenetic changes are a target for treatment.

RNA interference in steps

1. Double-stranded RNA is cut into short siRNA.
2. One strand of siRNA joins a protein complex.
3. The strand pairs with an mRNA with a complementary base sequence.
4. The mRNA is hydrolysed and cannot be translated.

Remember: the gene is transcribed normally. The block is at translation.

Must-know distinctions

Compare	Point
Transcription factor vs RNAi	Factor acts on DNA, before mRNA is made; RNAi acts on mRNA, before the polypeptide is made
Methylation vs mutation	Methylation leaves the base sequence the same; mutation changes it
Oncogene vs tumour suppressor gene	Oncogene is too active; tumour suppressor gene is too inactive
Hypermethylation vs hypomethylation	Hyper silences a gene; hypo can raise expression
Benign vs malignant	Benign stays in place; malignant invades and metastasises

Tumours at a glance

Benign	Malignant
Slow growth	Faster growth
Distinct border	Irregular, invades surrounding tissue
No secondary tumours	Secondary tumours form
Cells look like normal tissue	Cells often less specialised, abnormal nuclei

Cancer genes

Event	Tumour suppressor gene	Oncogene
Normal job	Slows division, repairs DNA, triggers cell death	Proto-oncogene stimulates division when a signal arrives
Mutation	Loses function	Gains activity or is over-expressed
Abnormal methylation	Hypermethylation silences it	Hypomethylation raises expression
Effect on division	No check on division	Unchecked stimulation

Oestrogen and breast cancer: in some breast cancers, cells respond to oestrogen by dividing. Higher oestrogen levels, or exposure for longer, mean more divisions and more chances for a mutation to arise in replication.

Using the knowledge: genetic testing for faulty alleles (prevention), blocking receptors or silencing oncogene mRNA with siRNA (treatment), reversing methylation or restoring a working gene (cure).

Evaluating data: a short routine

1. Say what the figures show, with numbers quoted.
2. Calculate a change as (new − old) / old × 100, or a ratio of risks.
3. Say whether there is a correlation, and do not claim cause without evidence.
4. Comment on sample size, controls, matching, time period and confounders.
5. Say what further evidence would settle the question.

Small worked reminder: 30 of 200 people with a variant developed a disease and 10 of 400 without it did. Risks are 15% and 2.5%, so the relative risk is 6.0. A large ratio can still involve small absolute numbers, so quote both.

Worked reminders

Pairing an siRNA with its target. An mRNA region reads GAAGUCCAGG. The partner strand pairs A with U and G with C, base by base: CUUCAGGUCC. This strand can bind only an mRNA that contains the matching sequence, so the effect is specific to one gene.

Percentage fall after RNAi. A protein measured at 92 units in control cells and 35 units in treated cells has fallen by (92 − 35) / 92 × 100 = 62%. Some protein remains (38% of the control), so the knock-down is partial. Possible reasons are that not all of the mRNA was broken down, or that protein made earlier was still present.

Reading a reporter experiment. If an expression level rises only in cells that contain the receptor, the receptor is needed. If a drug that blocks the receptor keeps the level low, binding is needed. Say both, quoting figures.

Genetic and environmental influences

Type of evidence	What it can show	Limit
Identical vs non-identical twin pairs	A higher rate in identical pairs suggests a genetic influence	Identical pairs are not always 100% alike, so environment, chance and epigenetic change also matter
Comparison of carriers and non-carriers of an allele	Size of the extra risk	Most carriers may not be affected; other factors act
Comparison of exposed and unexposed groups	A link between an environmental factor and a cancer	Correlation only, unless confounders are controlled
Change in methylation with age or lifestyle	Environment can alter gene function	Needs a comparison group and large samples

Phenotype is the result of genotype and environment together. Epigenetics is one route by which the environment changes gene expression without changing the base sequence.

Command words

• Describe: state what happens, in order.
• Explain: give a reason for each step, linking cause and effect.
• Calculate: show the working and give units or a percentage sign.
• Evaluate: weigh strengths and limits of evidence, then reach a judgement.
• Suggest: apply what you know to an unfamiliar case.

Quick self-test

1. State what a hormone-receptor complex must do before it affects transcription.
2. Explain why a muscle cell lacking an oestrogen receptor does not respond to oestrogen.
3. State two epigenetic changes that inhibit transcription.
4. The acetylation of histones near a gene falls. Explain the effect on that gene.
5. Gene H mRNA falls from 250 to 40 units. Calculate the percentage change.
6. Methylation of a promoter rises from 6% to 52% of its sites. Calculate how many times higher it is.
7. Name the stage at which RNAi acts, and say what it targets.
8. Give one reason a benign tumour is usually less dangerous than a malignant one.
9. Hypermethylation of a tumour suppressor gene is found in tumour cells. Explain the effect.
10. A tumour starts from one cell dividing every day. State the number of cells after 20 divisions, if none die.

Answers

1. It must enter the nucleus and bind to a specific DNA sequence near the target gene.
2. The hormone cannot bind without the receptor, so no complex forms and the gene is not switched on.
3. Increased DNA methylation and decreased histone acetylation.
4. Histones attract DNA more strongly, so DNA is more tightly wound, transcription factors cannot bind and transcription is reduced.
5. (40 − 250) / 250 × 100 = −84%, a fall of 84%.
6. 52 / 6 = 8.7 times higher (2 significant figures). The rise is 46 percentage points.
7. Translation. It targets mRNA with a complementary sequence.
8. A benign tumour does not metastasise, so it does not form secondary tumours.
9. The gene is silenced, so its product that slows division or repairs DNA is not made and division is not checked.
10. 2 to the power 20 = 1 048 576 cells.

Where marks are usually lost

• Writing that oestrogen itself binds to DNA; the receptor complex does.
• Forgetting the nuclear pore or the specific base sequence in a transcription factor answer.
• Saying methylation or acetylation “mutates” a gene.
• Reversing acetylation: more acetylation gives looser DNA and more transcription.
• Putting RNAi at transcription, or saying it destroys DNA.
• Describing an oncogene as a gene that is “switched off”.
• Writing “cancer” for any tumour, or “benign cancer”.
• Calling a correlation proof, or ignoring sample size in an evaluation.

Official syllabus

AQA AS and A-level Biology specification (7401 and 7402), for first teaching 2015, sections 3.8.2.2 and 3.8.2.3 (version 1.5), published by AQA.