OxfordAQA International AS and A-level Biology: Regulation of gene expression and stem cells (9610) – Revision Notes

These notes condense section 3.4.9 of the OxfordAQA International AS and A-level Biology (9610) specification, Version 5.1 (Unit 4, Control): 3.4.9.1 epigenetics and cancer genes, 3.4.9.2 RNA interference and 3.4.9.3 stem cells. For full explanations and worked examples use the study guide, then try the practice questions. Course pages: hub, checklist and free diagnostics.

3.4.9.1 Epigenetics

Definition to learn: an epigenetic change is a change in gene function without any change in the DNA base sequence. The change is preserved when cells divide.

Change	What happens	Result
Increased DNA methylation	Methyl groups added to DNA, often at a gene’s promoter	Gene harder to transcribe
Decreased histone acetylation	Fewer acetyl groups on histones	Histones keep a strong attraction to DNA, DNA tightly packed, less access for RNA polymerase and transcription factors
Increased histone acetylation	More acetyl groups	Looser DNA, more transcription

Key reasoning chain for acetylation: histones are positively charged, DNA is negatively charged, acetylation reduces the attraction, DNA loosens, transcription machinery binds, more mRNA.

Must-know distinction: methylation is not a mutation. No base is added, lost or swapped. Marks can be reversed; mutations cannot be undone in the same way.

Link to inheritance in cell lines: the pattern is copied on replication, so daughter cells keep the same silenced or active genes. That is how a specialised cell stays specialised.

Cancer genes

Gene type	Normal role	How cancer develops
Proto-oncogene	Stimulates division under control	Mutation or loss of methylation produces an oncogene that is overactive
Tumour suppressor gene	Slows division, repairs DNA, triggers apoptosis	Mutation, or increased methylation of its promoter, switches it off

Faulty methylation works in both directions: hypermethylation silences tumour suppressor genes, hypomethylation can over-activate oncogenes.

Using this knowledge (interpretation skill)

• Prevention: genetic testing for variants in tumour suppressor genes (BRCA1 and BRCA2 are examples) identifies higher-risk people, who can have extra screening or preventive surgery or change lifestyle.
• Treatment: drugs aimed at an overactive oncogene product (HER2 antibodies are an example); drugs that reverse abnormal methylation or acetylation to reactivate tumour suppressor genes; gene therapy to add a working tumour suppressor allele.
• Caution: a variant raises risk and does not guarantee cancer; targeted drugs may fail if tumour cells differ; epigenetic drugs can affect genes in healthy cells too.

Method: reading a methylation or risk table

1. State the trend in plain words, quoting values with units.
2. Calculate a ratio or percentage change and show the working.
3. Say what the data show (a link) and what they do not show (cause).
4. Suggest a control or intervention that would test cause.

Small worked reminder: promoter methylation is 12% in healthy tissue and 60% in a tumour, so it is 60 / 12 = 5 times higher. mRNA falls from 40 units to 10 units, a decrease of (40 − 10) / 40 × 100 = 75%. A higher methylation level goes with lower expression.

3.4.9.2 RNA interference

miRNA and siRNA are short RNA molecules, around 20 to 25 nucleotides long. They attach to mRNA of target genes and change gene activity (raising or lowering it).

	siRNA	miRNA
Matching to mRNA	Complementary over its whole length	Often only partly complementary
Typical effect	mRNA cut and broken down	Translation blocked, or mRNA broken down
Acts on	mRNA, not DNA	mRNA, not DNA

Steps for a decrease in protein:

1. Small RNA is loaded into a protein complex.
2. Its sequence pairs by complementary bases with the target mRNA.
3. The mRNA is degraded, or ribosomes are prevented from translating it.
4. Less protein is made, so gene activity falls.

Quick check on the effect size: if a protein falls from 250 units to 60 units after siRNA treatment, the decrease is (250 − 60) / 250 × 100 = 76%. Some protein remains, so describe it as reduced, not removed.

Common application: siRNA designed against an oncogene mRNA reduces the cancer-promoting protein in research settings.

3.4.9.3 Stem cells

Only part of a cell’s DNA is translated in a specialised cell. During development, only some of a cell’s DNA is translated, and that is how specialisation arises.

Potency	Forms	Where
Totipotent	All cell types and a whole organism	Limited time in mammalian embryos only
Pluripotent	Many cell types, not a whole organism	Found in the adult
Multipotent	A limited set of related cell types	Found in the adult
Unipotent	A single cell type	Found in the adult

Order from widest to narrowest: totipotent, pluripotent, multipotent, unipotent.

Evaluation checklist for stem cell therapies

Consider	Points
Benefits	Replace damaged tissue; treat blood disorders by bone marrow transplant; own cells avoid rejection; alternative to donor shortage
Risks	Tumour formation; rejection; infection; unproven long-term safety
Ethics	Use of embryos, consent, access and cost
Evidence	Sample size, control group, follow-up length, size of effect

Conclude: give a judgement, such as “worth using for X because the benefit is large, but the risk needs monitoring”.

Small worked reminder: if 30 of 60 treated patients improve (50%) and 12 of 60 controls improve (20%), the difference is 30 percentage points. The benefit is clear, but 20% of controls improved without treatment.

Answer frames to rehearse

“Explain how increased methylation can lead to cancer.” A tumour suppressor gene has a methylated promoter. Its transcription falls and less of its protein is made. The cell loses a brake on division, DNA repair or apoptosis, so damaged cells keep dividing. Extra changes in other genes are usually needed before a tumour forms.

“Show how mutating a proto-oncogene can end in a tumour.” The mutation makes the protein overactive, or makes too much of it. The cell receives a constant signal to divide. Division becomes uncontrolled and a mass of cells forms.

“Describe how siRNA reduces the activity of a gene.” The siRNA joins a protein complex. It binds to mRNA with a complementary sequence. The mRNA is broken down, so it cannot be translated and less protein is made.

“Suggest why bone marrow stem cells are described as multipotent.” They divide to form several related cell types, such as red cells and white cells, but not every cell type in the body.

Must-know contrasts

Pair	Difference
Methylation and mutation	Methylation leaves the base sequence alone; mutation changes it
Oncogene and proto-oncogene	The oncogene is the overactive form of the normal gene
siRNA and miRNA	siRNA pairs fully with its target; miRNA pairs partly
Totipotent and pluripotent	Only totipotent cells can form a whole organism
Multipotent and unipotent	Several related cell types against one

Quick self-test

1. Define an epigenetic change.
2. Explain why increased methylation of a promoter lowers transcription.
3. Why does decreased histone acetylation reduce transcription?
4. Name the two types of gene that, when altered, lead to uncontrolled division, and say what each normally does.
5. Promoter methylation rises from 8% to 56%. How many times higher is it?
6. What is the difference between how siRNA and miRNA pair with mRNA?
7. A protein falls from 480 units to 120 units after siRNA treatment. Calculate the percentage decrease.
8. Which potency type is present only briefly in early mammalian embryos?
9. Name one cell type that is multipotent.
10. Give two risks of using stem cells to treat a disorder.
11. In a study, 24 of 200 variant carriers and 6 of 200 non-carriers developed a cancer. Calculate the percentage in each group and the risk ratio.

Answers

1. A change in gene function without a change in the DNA base sequence, preserved when cells divide.
2. Methylation makes the gene harder for the transcription machinery to use, so less mRNA is made.
3. Histones keep a strong attraction to DNA, so it stays tightly packed and RNA polymerase and transcription factors cannot easily bind.
4. Proto-oncogenes stimulate cell division in a controlled way. Tumour suppressor genes slow division, repair DNA or trigger apoptosis.
5. 56 / 8 = 7 times higher.
6. siRNA is fully complementary to its target mRNA. miRNA is often only partly complementary.
7. (480 − 120) / 480 × 100 = 75%.
8. Totipotent.
9. A bone marrow stem cell that forms blood cells.
10. Any two from: tumour formation, rejection, infection, ethical objections, high cost, unproven long-term safety.
11. 24 / 200 × 100 = 12%; 6 / 200 × 100 = 3%; risk ratio = 12 / 3 = 4.

Where marks are usually lost

• Writing “methylation changes the DNA” without saying the base sequence stays the same.
• Describing acetylation as making DNA tighter. It loosens it.
• Missing the idea of access: RNA polymerase and transcription factors need to reach the promoter.
• Saying tumour suppressor genes cause cancer, instead of saying that losing them removes the brakes.
• Forgetting that hypermethylation and hypomethylation have opposite effects on tumour suppressor genes and oncogenes.
• Saying siRNA acts on DNA or on the gene itself. It binds to mRNA.
• Giving figures from a table with no units or no calculation when the question asks you to use the data.
• Stating a cause from correlation data.
• Listing stem cell advantages with no risks, or the reverse, when the command word is evaluate.

Official syllabus

OxfordAQA, International AS and A-level Biology (9610), Version 5.1, section 3.4.9 (3.4.9.1 to 3.4.9.3). Check oxfordaqa.com/9610 for the current specification.