AQA A-level Biology: Gene Mutations and Stem Cells (7402) – Revision Notes

These notes condense sections 3.8.1 and 3.8.2.1 of the AQA specification for AS and A-level Biology (7401 and 7402), first teaching 2015. Neither section is part of the AS. The study guide has the full explanations and further worked examples; afterwards, test yourself with the practice questions. The AQA A-level Biology hub and the printable checklist cover the wider course. The free diagnostics show which topics need work. Related earlier content: mutation and meiosis.

Key definitions

• Gene mutation: an alteration to the order of bases in DNA.
• Spontaneous mutation: arises without an outside cause, for example a copying error during DNA replication.
• Mutagenic agent: something that increases the mutation rate.
• Degenerate code: several different triplets can specify the same amino acid.
• Frame shift: a mutation that changes every triplet downstream of it.
• Totipotent: can divide and produce any type of body cell.
• Pluripotent: found in embryos; can form many cell types; can divide without limit.
• Multipotent: found in mature mammals; forms a limited number of cell types.
• Unipotent: found in mature mammals; forms one cell type, for example cardiomyocytes.
• iPS cell: induced pluripotent stem cell, made from an adult somatic cell using protein transcription factors.

3.8.1 Mutations at a glance

Type	Change	Frame shift?
Substitution	One base replaced	No
Addition	Base or bases inserted	Yes, unless a multiple of three
Deletion	Base or bases lost	Yes, unless a multiple of three
Duplication	Section repeated	Yes, unless a multiple of three
Inversion	Section reversed end to end	No (length unchanged)
Translocation	Section moved elsewhere	Possible at each site, if not a multiple of three

Method: relate a mutation to the polypeptide

1. Write the original mRNA as triplets and translate it using the codon data supplied.
2. Identify the type of mutation and the triplet or triplets it touches.
3. Rewrite the mRNA from the mutation onwards, regrouping into triplets.
4. Translate again and compare. Count how many amino acids changed and whether a stop codon appeared or disappeared.
5. State the type of effect: unchanged (degenerate code), one amino acid changed, shorter polypeptide, or every amino acid downstream changed (frame shift).
6. If asked about function, link the new primary structure to tertiary structure and the shape of an active site or binding site.

Worked reminder: one gene, four mutations

mRNA: AUG AAA GUU GAU CCA UGA. Codon data supplied: AUG Met; AAA Lys; GUU and GUC Val; GAU Asp; GAA Glu; CCA Pro; UGA, UAA stop; AAG Lys; UUG Leu; AUC Ile; CAU His.

Original: Met-Lys-Val-Asp-Pro, then stop.

Mutation	New mRNA	Result
GUU to GUC	AUG AAA GUC GAU CCA UGA	Met-Lys-Val-Asp-Pro: unchanged
GAU to GAA	AUG AAA GUU GAA CCA UGA	Asp becomes Glu: one amino acid changed
AAA to UAA	AUG UAA GUU GAU CCA UGA	Met only: stop codon too early
First A of AAA deleted	AUG AAG UUG AUC CAU GA	Met-Lys-Leu-Ile-His: frame shift, stop codon lost

Notice that a frame shift can replace or remove the stop codon, so a polypeptide may become longer as well as wrong.

Must-know distinctions

• A silent change versus no change. The bases differ but the polypeptide is identical. Say both.
• Deletion of one base versus deletion of three. One base shifts the frame. Three bases lose one amino acid and keep the frame.
• Substitution versus inversion. A substitution changes one base. An inversion reverses a section and may change several amino acids without changing the length.
• Spontaneous versus induced. Spontaneous mutations happen at a low background rate. Mutagenic agents raise that rate.

Worked reminder: spot the type from two sequences

Original coding strand: ATG GCA TTC AAG TGA, giving Met-Ala-Phe-Lys, then stop. Codon data supplied: Phe is coded by UUC and UUU; Leu by CUU; Glu by GAA; Ser by UCA and AGU.

• ATG GCA TTC TTC AAG TGA. Three extra bases, a repeat of TTC, so this is a duplication. The frame is kept, so the result is Met-Ala-Phe-Phe-Lys: one extra Phe.
• ATG GCA CTT GAA TGA. The section TTCAAG now reads CTTGAA, so it has been reversed end to end: an inversion. The length is the same, and two amino acids change: Met-Ala-Leu-Glu.
• ATG GCA TCA AGT GA. The first T of TTC is missing, so this is a deletion of one base. It is a frame shift: Met-Ala-Ser-Ser, and the stop codon is lost.

Worked reminder: judging a trial

A trial reports that 18 of 30 patients given a stem cell therapy improved, against 9 of 30 given standard care. That is 18 ÷ 30 × 100 = 60% against 9 ÷ 30 × 100 = 30%, a difference of 30 percentage points. A good evaluation then asks: are 30 patients per group enough, were patients allocated fairly, how long were they followed, were tumours or other harms recorded, and can the result be repeated? Finish with a judgement.

3.8.2.1 Cell potency

Cell	Cell types it can form	Where found
Totipotent	Any type of body cell	Early mammalian embryo, for a limited time
Pluripotent	Many types; divides in unlimited numbers	Embryos
Multipotent	A limited number	Mature mammals
Unipotent	One	Mature mammals

Why cells specialise

All cells from a zygote by mitosis have the same genes. During development, cells translate only part of their DNA, so each type makes a different set of proteins. Specialisation does not involve losing genes.

iPS cells in steps

1. Take adult somatic cells, for example skin cells, from the patient.
2. Treat them with appropriate protein transcription factors.
3. The transcription factors switch on genes that give pluripotency.
4. The cells become pluripotent and can be grown and made to differentiate into the cell type needed.

Evaluating stem cell treatments

Question	Points to make
Is a source ethical?	Embryonic stem cells involve destroying an embryo; adult and iPS cells do not
Will the patient reject it?	The patient’s own adult or iPS cells are less likely to be rejected
Is it effective?	Compare improvement with a control group; look at sample size and follow-up
Is it safe?	Pluripotent cells dividing without limit may form tumours
Is it practical?	Reprogramming is inefficient; multipotent cells are limited in range

End with a judgement that weighs the points.

Tissue culture of cauliflower explants

The specification suggests this as an opportunity for aseptic technique. Cut explants, sterilise, place on sterile nutrient agar with growth regulators, incubate, and watch for callus and shoots. It shows that plant cells can keep the ability to form every cell type. It is not listed as a required practical.

Quick self-test

1. Name the six types of gene mutation in the specification.
2. Explain why a substitution can leave a polypeptide unchanged.
3. What is a frame shift?
4. A coding region, including its stop codon, has 1500 bases. How many amino acids are in the polypeptide?
5. A substitution changes a codon for Lys to a stop codon. What happens to the polypeptide?
6. Which type of cell can produce any type of body cell?
7. Where are pluripotent cells found?
8. Give an example of unipotent cell formation.
9. Describe how iPS cells are made.
10. Of 45 cauliflower explants, 36 produce callus. Calculate the percentage.
11. A culture grows from 6.0 × 10⁶ to 2.4 × 10⁷ cells, a four-fold rise. How many doublings is this?
12. Give one advantage and one risk of using iPS cells in treatment.

Answers

1. Addition, deletion, substitution, inversion, duplication and translocation.
2. Several triplets specify the same amino acid, so the new triplet can still give the original one.
3. A mutation that changes the nature of all base triplets downstream of it, as when bases are added or lost in a number that is not a multiple of three.
4. 1500 ÷ 3 = 500 triplets, minus one stop codon = 499 amino acids.
5. Translation stops early, giving a shorter polypeptide.
6. A totipotent cell.
7. In embryos.
8. The formation of cardiomyocytes.
9. Take adult somatic cells and treat them with protein transcription factors that switch on genes giving pluripotency.
10. 36 ÷ 45 × 100 = 80%.
11. Two doublings (2 × 2 = 4).
12. Advantage: made from the patient’s own cells, so no embryo is destroyed. Risk: the cells may form tumours.

Where marks are usually lost

• Describing a mutation as “a change in the gene” without saying which triplet changed and what amino acid change followed.
• Forgetting the degenerate code when explaining why a polypeptide is unchanged.
• Treating every addition or deletion as a frame shift without checking whether the number of bases is a multiple of three.
• Saying a frame shift changes only the next amino acid.
• Mixing up totipotent and pluripotent.
• Claiming specialised cells have lost or gained genes instead of translating only part of their DNA.
• Describing iPS cells as taken from embryos.
• Listing only benefits or only risks of stem cell therapy and giving no judgement.

Official syllabus

Source: AQA, AS and A-level Biology (7401 and 7402), specification for first teaching 2015, version 1.5, sections 3.8.1 and 3.8.2.1.