Key Idea: A mutation is a random change to the base sequence of DNA. It is the original source of all new alleles, and so of the genetic variation that drives evolution. This topic follows mutations from the smallest scale to the largest: a single base swapped (gene mutation), up to a whole chromosome gained or lost (chromosome mutation). It then turns to the tools we use to read and rewrite DNA — gene editing / genetic modification and DNA profiling. D1.3 is a regular across all papers: quick Paper 1A MCQs (a true feature of mutations; reading a gel), Paper 1B data-reasoning (classify a mutation from two base sequences), Paper 2 extended answers (the sickle-cell cascade; non-disjunction; describing PCR) and Paper 3 on the genetic-engineering toolkit.
Scale of a mutation: a gene (point) mutation changes a few bases; a chromosome mutation changes whole chromosomes. Two biotech toolkits: gene editing / GM changes an organism's DNA; DNA profiling reads DNA to identify an individual. Don't confuse rewriting DNA with reading it.
🧬 Types of mutation (4.3.1)
A gene mutation changes a single base (or a few). There are three kinds, and the key is whether a base is swapped, added or removed. DNA is read in triplets (codons), so whether the total number of bases changes decides how big the effect is.
| Mutation type | What changes in the DNA | Effect on the reading frame |
|---|---|---|
| Substitution | one base is swapped for a different base | no shift — at most the one codon containing that base changes |
| Insertion | an extra base is added into the sequence | shifts the reading frame from that point on (a frameshift) |
| Deletion | a base is removed from the sequence | shifts the reading frame from that point on (a frameshift) |
Substitution: One base is **swapped** for another. Total number of bases **stays the same**. Reading frame is **not** shifted. Usually affects **one codon** only.
Insertion / Deletion: A base is **added** (insertion) or **removed** (deletion). Total number of bases **changes**. Reading frame is **shifted** (a frameshift). Usually affects **every codon downstream**.
Key Idea: The Paper 1B favourite gives two base sequences (before and after) and asks you to classify the change: Same number of bases, one letter different → substitution. One more base → insertion. One fewer base → deletion — and both of these cause a frameshift that changes every triplet after the change.
Sub = substitute (swap). Insertion = put one in. Deletion = take one out. Only insertion and deletion change the number of bases — and changing the number is what causes a frameshift. Mutations are the source of new alleles, and can be harmful, neutral or beneficial — never 'always harmful'.
🩺 Germline vs somatic, mutagens & cancer (4.3.2)
What a mutation does next depends on which cell it strikes. A germline mutation (in a gamete or gamete-forming cell) can be inherited; a somatic mutation (in any other body cell) cannot. Mutagens — UV light, X-rays, the chemicals in tobacco smoke — raise the mutation rate. A mutagen that causes cancer is a carcinogen.
| Feature | Germline mutation | Somatic mutation |
|---|---|---|
| Which cell | a gamete (egg/sperm) or gamete-forming cell | any other body cell (skin, lung, gut...) |
| Can it be inherited? | YES — passed to offspring | NO — stays in the individual |
| Who carries it | every cell of any child who inherits it | only cells descended from the mutated cell |
| Linked to cancer? | no (only inherited risk genes) | yes — if a cell-division gene mutates |
Cancer is a chain of events: A mutagen damages a cell's DNA → a mutation arises in a gene that controls cell division → the cell divides uncontrollably → over time several mutations accumulate → a tumour forms, which may become malignant and spread (metastasis). Cancer usually needs an accumulation of several mutations, not just one — which is why risk rises with repeated exposure and with age.
The cancer chain — four scoring steps
- Mutagen damages the DNA of a body cell
- Mutation occurs in a gene controlling cell division (the cell cycle)
- The cell divides uncontrollably
- Mutations accumulate and the cells form a tumour (may become malignant / spread)
To tell germline from somatic, ask: could this mutation be passed to a child? A gamete (egg/sperm) or gamete-forming cell → germline → heritable. Any other body cell → somatic → not heritable. Cancer is almost always a somatic event — only the risk can run in families.
🔴 Sickle-cell anaemia — mutation to phenotype (4.3.3)
Sickle-cell anaemia shows how one base can change a whole organism. A single base substitution in the haemoglobin gene ripples up through the mRNA, the protein, the red blood cell and finally the person's phenotype. The marks come from naming the cascade in order — each step causing the next.
The pathway a gene mutation travels down: DNA gene -> mRNA -> polypeptide. Change ONE base in the gene and a single codon — and so a single amino acid — changes at the bottom. This is exactly how a base substitution causes sickle-cell anaemia.
🔒 Interactive diagram
Explore the labelled diagram, charts and maps for this topic in study mode.
| Level | What changes | How big is the change? |
|---|---|---|
| DNA (the gene) | one base is substituted for another | a single base out of hundreds |
| mRNA | the codon copied from that part changes | one 3-base codon |
| Amino acid | glutamic acid is replaced by valine | one amino acid out of ~146 |
| Protein (haemoglobin) | abnormal HbS is made; it sticks together when oxygen is low | one protein behaves differently |
| Red blood cell | the cell collapses into a rigid sickle shape | whole cells change shape |
| Phenotype | blocked capillaries, less oxygen carried, pain, anaemia | the whole organism is affected |
One base → one codon → one amino acid (glutamic acid → valine) → faulty haemoglobin (HbS) → sickled cells → sickle-cell anaemia. Name the glutamic acid → valine swap — that detail separates a top answer. Only one base and one amino acid change; never say 'the whole protein is rewritten'.
⚠️ Chromosome mutations & non-disjunction (4.3.4)
A chromosome mutation is bigger than a gene mutation: a whole chromosome is gained or lost. The usual cause is non-disjunction — chromosomes (in meiosis I) or sister chromatids (in meiosis II) fail to separate, so one gamete gets an extra copy and another gets none. Recall what normal meiosis should do — non-disjunction is the failure of exactly these separation steps.
Normal meiosis: homologous chromosomes separate in meiosis I and sister chromatids separate in meiosis II, so every gamete ends up with the correct, halved chromosome number. Non-disjunction is the FAILURE of one of these separation steps.
🔒 Interactive diagram
Explore the labelled diagram, charts and maps for this topic in study mode.
| Stage | What happens | Chromosome number |
|---|---|---|
| Non-disjunction in meiosis | chromosome 21 fails to separate | both copies go to one gamete |
| Abnormal gamete | carries an extra chromosome 21 | n + 1 (two copies of 21) |
| Fertilisation by a normal gamete | the normal gamete adds one more copy | 2n + 1 (three copies of 21) |
| Resulting individual | every cell (made by mitosis) carries the extra chromosome | trisomy 21 = Down syndrome |
| Feature | Gene (point) mutation | Chromosome mutation |
|---|---|---|
| Scale of change | a few DNA bases within one gene | a whole chromosome added or lost |
| Typical cause | replication error or a mutagen | non-disjunction during meiosis |
| Visible on a karyogram? | no — far too small to see | yes — an extra/missing whole chromosome shows |
| Example | sickle-cell anaemia (one base substitution) | Down syndrome (trisomy 21) |
'Disjunction' means separating, so non-disjunction = not separating. Chromosomes that should go to opposite ends instead go to the same end — one gamete gets too many, the other too few. Trisomy = three copies; aneuploidy = an abnormal chromosome number. Incidence of Down syndrome rises steeply with maternal age.
✂️ Gene editing & genetic modification (4.3.5)
Genetic modification deliberately changes an organism's DNA — usually by adding a gene from another species (a transgenic organism) or by editing an existing gene. To transfer a gene, the cell's own molecular tools are borrowed: enzymes that cut DNA, an enzyme that joins it, and a vector that carries it in.
| Step | What happens | Tool used |
|---|---|---|
| 1. Cut out the gene | the wanted gene is cut from the source DNA (sticky ends) | restriction enzyme |
| 2. Open the vector | the SAME enzyme opens the plasmid → matching sticky ends | restriction enzyme |
| 3. Join them | the sticky ends pair up and the join is sealed | DNA ligase → recombinant DNA |
| 4. Insert into host | the recombinant plasmid is taken up by the host cell (transformation) | vector / plasmid |
| 5. Express the gene | the host copies and uses the gene, making the GM organism | host cell |
Restriction enzyme — the scissors: **Cuts** DNA at a specific recognition sequence. Leaves matching **sticky ends**. The **same** enzyme cuts the gene AND the vector. So their ends are **complementary** and can pair up.
DNA ligase — the glue: **Joins** the gene into the vector. Re-forms the **sugar–phosphate** backbone. Makes one continuous **recombinant DNA** molecule. Seals the join so the plasmid is whole again.
Key Idea: Older methods mainly add a gene. CRISPR-Cas9 lets scientists edit a gene already in the cell, far more precisely. A short guide RNA is made to match one chosen DNA sequence; it leads the Cas9 protein there, where Cas9 cuts the DNA. During repair a gene can be knocked out, corrected or have a piece inserted — which is why CRISPR is a tool for gene editing, not just gene transfer.
| Possible advantage of GM | Possible concern |
|---|---|
| higher yield / less crop lost to weeds or pests | GM genes might spread to wild plants or weeds |
| less herbicide or pesticide may be needed overall | long-term effects on health/ecosystems are uncertain |
| crops made more nutritious or drought-tolerant | a few large companies may control patented seeds |
| bacteria can mass-produce medicines (e.g. insulin) | some people have ethical / 'unnatural' objections |
Restriction enzyme CUTS (scissors); DNA ligase JOINS (glue); the vector CARRIES the gene into the host; the host EXPRESSES it. Never say ligase cuts, or the restriction enzyme joins — that swap is the most common slip.
🔬 DNA profiling: PCR & gel electrophoresis (4.3.6)
DNA profiling reads the parts of a person's DNA that differ most between individuals, giving a near-unique pattern. It works in two stages: copy first (PCR makes enough DNA to see), then separate (gel electrophoresis spreads the fragments by size).
| Step of a PCR cycle | Temperature | What happens |
|---|---|---|
| Denaturation | ~95 °C (hot) | heat breaks the hydrogen bonds, so the double helix splits into two single strands |
| Annealing | ~55 °C (cooler) | short primers bind (anneal) to each single strand, marking where copying begins |
| Extension | ~72 °C | Taq DNA polymerase adds nucleotides, building a new complementary strand |
PCR (copy): **Amplifies** the DNA (makes millions of copies). Cycles of **denaturation → annealing → extension**. Uses **primers** and heat-stable **Taq polymerase**. Each cycle **doubles** the amount of DNA.
Gel electrophoresis (sort): **Separates** the DNA by size. Driven by an **electric field**. DNA is **negative** → moves to the **anode (+)**. **Smaller fragments travel further**.
Key Idea: 1. DNA is negatively charged, so all fragments are pulled toward the anode (the + electrode). 2. Smaller fragments travel further — they slip through the gel mesh more easily, while large fragments stay near the wells. So the band nearest the + end is always the shortest fragment.
PCR = Plenty of Copies Rapidly (amplify). Gel = a race where the small runners win — smaller fragments travel furthest toward the + end. Copy first with PCR, then sort by size on the gel — don't swap the two jobs.
✍️ Worked examples
IB-style question — classify a mutation from two sequences
A length of DNA normally reads T A C G G A C T T (in triplets). After a mutation it reads T A C G T A C T T. Classify the mutation and justify your answer. [2]
How to score both marks:
Compare base by base. The first and last triplets are unchanged; in the middle, G G A has become G T A — the middle G has become a T.
Decide what happened. One base has been swapped for another, and the total number of bases is unchanged (still 9) — no base added or removed.
Classify and justify. This is a substitution — one base replaced by another, number of bases unchanged, so the reading frame is not shifted. (Mark 1: substitution. Mark 2: one base replaced / number unchanged.)
Substitution — one base (G) has been replaced by another (T); the number of bases is unchanged, so the reading frame is not shifted.
IB-style question — outline the sickle-cell cascade
Outline how a single DNA base substitution leads to sickle-cell anaemia at the molecular level. [4]
How to score all four marks:
Start at the gene. One base is substituted in the DNA of the haemoglobin gene, creating a new allele.
Move to the mRNA / amino acid. This changes one mRNA codon, so one amino acid changes — glutamic acid is replaced by valine.
Reach the protein. The result is abnormal haemoglobin (HbS) that sticks together into fibres when oxygen is low.
Reach the cell. The red blood cells are pulled into a rigid sickle shape — the cause of sickle-cell anaemia. (1 mark per linked step, max 4.)
A base substitution in the haemoglobin gene changes one codon, so one amino acid changes (glutamic acid → valine); this makes abnormal HbS that sticks together at low oxygen, pulling red blood cells into a rigid sickle shape.
Visual recap of mutation-to-phenotype: one base substitution in the haemoglobin gene -> one altered mRNA codon -> one altered amino acid (glutamic acid becomes valine) -> abnormal haemoglobin (HbS) -> sickled red blood cells.
🔒 Interactive diagram
Explore the labelled diagram, charts and maps for this topic in study mode.
IB-style question — non-disjunction & Down syndrome
Explain how meiotic non-disjunction can result in Down syndrome (trisomy 21). [3]
How to score all three marks:
Name the failure. During meiosis, non-disjunction occurs — chromosome 21 fails to separate, so both copies pass into the same gamete.
Describe the abnormal gamete. This makes a gamete with an extra chromosome 21 (n + 1).
Add fertilisation. When this gamete is fertilised by a normal one, the zygote has three copies of chromosome 21 (trisomy 21) — Down syndrome. (Mark 1: fail to separate. Mark 2: gamete with extra 21. Mark 3: fertilisation → three copies.)
Non-disjunction means chromosome 21 fails to separate, so one gamete carries two copies; at fertilisation a normal gamete adds a third, giving trisomy 21 (Down syndrome).
Visual recap of non-disjunction: if a chromosome (or chromatid) fails to separate, one gamete gains an extra copy (n + 1) and another gets none. Fertilising the n + 1 gamete gives three copies of that chromosome — trisomy (e.g. trisomy 21 = Down syndrome).
🔒 Interactive diagram
Explore the labelled diagram, charts and maps for this topic in study mode.
IB-style question — describe the steps of PCR
Describe the steps of the polymerase chain reaction (PCR) used to amplify a sample of DNA. [4]
How to score all four marks:
Denaturation. The DNA is heated to about 95 °C, breaking the hydrogen bonds and separating the double helix into two single strands.
Annealing. The mixture is cooled to about 55 °C so short primers bind (anneal) to the start of each strand.
Extension. At about 72 °C, Taq DNA polymerase adds nucleotides to each primer, building a new complementary strand.
Cycling. The three steps are repeated many times, and the DNA doubles each cycle, making millions of copies. (1 mark each for the three steps and for the repeated cycling/doubling.)
Heat (~95 °C) denatures the DNA into single strands; cooling (~55 °C) lets primers anneal; Taq polymerase (~72 °C) extends a new complementary strand; the cycle repeats, doubling the DNA each time.
✅ Quick self-check
Tap each card to check yourself.
What is a mutation, and how do the three gene types differ? A random change to the DNA base sequence — the source of new alleles. Substitution swaps one base (number unchanged); insertion adds a base; deletion removes one. Only insertion and deletion change the number of bases, causing a frameshift.
Germline vs somatic — and which can be inherited? A germline mutation (in a gamete or gamete-forming cell) can be inherited; a somatic mutation (any other body cell) cannot. Cancer is a somatic event — only the risk can run in families.
How does a mutation lead to cancer? A mutagen causes a mutation in a gene controlling cell division; the cell divides uncontrollably; mutations accumulate; the cells form a tumour that may become malignant and spread.
The sickle-cell cascade in order? Base substitution → one mRNA codon changes → one amino acid changes (glutamic acid → valine) → abnormal HbS → sickled red blood cells → anaemia, pain, less oxygen carried.
How does non-disjunction cause Down syndrome? Chromosome 21 fails to separate in meiosis, so a gamete gets an extra copy; fertilisation by a normal gamete adds a third copy → trisomy 21. It is a whole-chromosome change, visible on a karyogram.
Gene editing vs DNA profiling — the tools? GM rewrites DNA: a restriction enzyme cuts, DNA ligase joins into recombinant DNA, a vector carries it in; CRISPR-Cas9 edits with a guide RNA + Cas9. Profiling reads DNA: PCR copies it, gel electrophoresis sorts fragments by size (smaller travel further to the + anode).
Exam Tips
- Classify a mutation by counting bases: same number = substitution; one more = insertion; one fewer = deletion. Only insertion and deletion cause a frameshift.
- 'A feature of mutations' safe answers: random, a change to the base sequence, the source of new alleles. They are NOT always harmful.
- Asked which mutation can be inherited? The one in a gamete / gamete-forming (germline) cell — never an ordinary body cell.
- The cancer chain needs SEPARATE steps: mutagen → mutation in a cell-division gene → uncontrolled division → tumour. A 4-mark outline = four distinct points.
- For the sickle-cell outline, give the cascade IN ORDER and name the glutamic acid → valine swap. Only one base and one amino acid change.
- Non-disjunction changes the NUMBER of whole chromosomes — never describe it as changing DNA bases. Give the full chain to trisomy 21.
- Gene-transfer tools in order: restriction enzyme CUTS (same enzyme cuts gene and vector → matching sticky ends), ligase JOINS, vector CARRIES. State ligase's role as joining/sealing, never cutting.
- DNA profiling: PCR is the amplification (copying) stage; gel electrophoresis separates by size. DNA is negative → moves to the anode (+), and smaller fragments travel further.
Key Idea: Mutations are random changes to the DNA base sequence and the source of new alleles. Gene mutations (4.3.1): substitution (swap), insertion (add) and deletion (remove) — insertion and deletion cause a frameshift. Germline vs somatic (4.3.2): only germline (gamete) mutations are inherited; mutagens raise the rate and can drive a somatic cell to cancer (mutation in a cell-division gene → uncontrolled division → tumour). Sickle-cell (4.3.3): one base substitution → glutamic acid → valine → HbS → sickled cells — a tiny change with a whole-body effect. Chromosome mutations (4.3.4): non-disjunction in meiosis → a gamete with an extra/missing chromosome → trisomy (e.g. Down syndrome). Biotech: gene editing / GM (4.3.5) rewrites DNA (restriction enzyme cuts, ligase joins, vector carries; CRISPR-Cas9 edits with guide RNA + Cas9); DNA profiling (4.3.6) reads DNA (PCR copies, gel electrophoresis sorts by size — smaller fragments travel further to the + anode).