3.8.1 is the chain that connects a single-base change in DNA to a working or broken protein. A substitution rewrites one codon; an addition or deletion shifts every subsequent codon; an inversion flips a segment in place. The chain ends at the protein's shape and at its function.
Read this topic as an analogy.
Imagine a building blueprint where every detail is specified by a three-letter code: which beam goes here, which joint type fits there, which kind of rivet, which orientation. The builder reads the codes in order, in groups of three, and assembles the building one specification at a time. Whether the building stands or falls comes down to what is written on the sheet, and how cleanly the builder can read it.
A single-letter typo is sensitive but not always destructive. Because the code is generous, several different triplets often spell the same beam, so a typo might leave the building unchanged. Sometimes the typo spells a different beam, and the build comes out with a slightly different part in one place. Sometimes the typo spells "stop building", and the work halts mid-way through the structure.
Add or remove one letter anywhere in the sheet and every subsequent triplet is re-grouped. From that point on, every beam is wrong, until the builder reads a "stop" code by accident and the half-finished structure is abandoned. Reverse a segment of letters in place, and that section of the building changes while the rest holds. Cut a segment out and paste it somewhere else, and a chunk of the building moves to a place it was never meant to sit, often disrupting whatever was meant to be there instead.
When the right beam is in the right place, the fasteners between that beam and its neighbours have to be the right kind too. Some joints take bolts, some take welds, some take rivets, and the choice depends on which beams meet. Change one beam, and the joints around it form differently or fail to form. Joints set the geometry. Geometry sets whether the building does what it was meant to do.
Two kinds of building have a special wrinkle. A heating-system building has a thermostat girder that switches on when an outside signal arrives, and switches off when the signal stops. Mistype the thermostat code so that it stays on, and the building keeps adding extensions whether or not the signal arrives. A brake-system building has a brake girder that holds expansion in check. Two ways to lose the brakes: mistype the brake code so the brakes go in mis-shaped and don't engage, or stick the brake pages of the blueprint together with tape so the builder never installs them in the first place. Either way, the building expands unchecked.
Mapping back to formal vocabulary. Three-letter code is a codon; the letter is a base. The beam is an amino acid; the order of beams is the primary structure. The fasteners are hydrogen, ionic, and disulfide bonds; the building's overall geometry is the tertiary structure. A typo is a mutation. The thermostat girder stuck on is the oncogene chain (gain of function). The mis-shaped brakes and the taped-shut brake pages are the two tumour suppressor routes (mutation route and methylation route, both loss of function). Use the formal terms in the exam answer; the blueprint is for understanding.
Five types of gene mutation change the base sequence in different ways.
A gene mutation is a change in the base sequence of DNA. AQA names five types beyond the simple substitution and deletion encountered earlier in the course. Each type produces a distinct structural consequence in the polypeptide, and the type determines whether the downstream reading frame survives the change.
The five named mutation types and their effect on the base count.
| Mutation type | What changes in the sequence | Total base count |
|---|---|---|
| Substitution | One base replaced by a different base | Unchanged |
| Addition | One or more bases inserted (duplication is a special case) | Rises |
| Deletion | One or more bases removed | Falls |
| Inversion | A segment reversed in place | Unchanged |
| Translocation | A segment moved to a different position or chromosome | Unchanged |
Substitution does not cause a frameshift. Frameshifts come from addition or deletion of bases. AQA rejects
frameshiftas the mutation type when the stem specifies a base substitution.
A frameshift occurs when the total base count changes by a number that is not a multiple of three. The reading frame downstream of the mutation point is offset by one or two bases, so every subsequent codon reads as a different triplet. Substitution, inversion, and translocation do not produce a frameshift.
Only deletion and addition change the total base count. Inversion, translocation, and a segment duplication leave the count in the affected region unchanged.
Mutations come from mutagens and from replication errors.
Gene mutations arise from external mutagenic agents and from intrinsic errors during DNA replication. Mutagens are split by chemical type and by radiation type; replication errors arise inside the cell whenever the polymerase machinery misreads a template.
The credited examples are alcohol, benzene, the carcinogens in tobacco tar, and asbestos fibres. They act by chemically modifying bases so that those bases pair incorrectly with the templated complement, or by inserting themselves between adjacent base pairs and causing insertion errors during the next round of replication.
Ionising radiation includes alpha particles, beta particles, ultraviolet light, and X-rays. These break covalent bonds or chemically modify bases, leaving the DNA either damaged or incorrectly templated. Replication errors occur when DNA polymerase introduces an incorrect nucleotide; most are corrected by proofreading, but the few that escape become heritable mutations.
A substitution propagates through three structural levels of the polypeptide.
The substitution chain is the single most consistently examined mechanism in 3.8.1. The chain has three identifiable steps, and each step is graded as its own independent mark. The chain starts at the base sequence and ends at the tertiary structure of the polypeptide; partial answers that stop early lose marks at every dropped step.
- The substitution changes one base in one codon. The codon now specifies a different amino acid, so the amino acid sequence, which is the primary structure of the polypeptide, changes at that position.
- The new amino acid carries a different R group. Hydrogen bonds, ionic bonds, and disulfide bonds that previously formed at that position now form differently, or fail to form, or form in a different place along the chain.
- The altered bonds change the overall fold. The tertiary structure of the polypeptide is changed; where the affected position sits inside a functional region, the protein loses or alters its function.
Name the bond type. Write
hydrogen,ionic, ordisulfideexplicitly. AQA rejectsbonds alteredwithout a named bond type.
Write
tertiary structure. AQA rejects3D shapeand rejectsactive siteas substitutes, andactive siteis rejected on any non-enzyme protein.
The chain is graded as three independent marks; stopping at primary structure or at the bonds without continuing to tertiary structure leaves the third mark unclaimed.
The substitution chain applies to substitution stems only. Frameshift mutations from addition or deletion follow a different chain. They typically introduce codons missing, amino acids missing, or a premature stop codon that truncates the polypeptide. The three-level chain above does not apply to them.
Bases code; amino acids do not. AQA rejects
amino acids code,amino acids are formed, anddifferent amino acids formed. The base sequence and the codons code for amino acids; the amino acids are the product.
Pitfall — Don't restate the stem
Don't restate the stem.
When a stem says "shorter polypeptide" or "altered protein", the explanation has to give the mechanism: codons missing, amino acids missing, a premature stop codon, or the three-step substitution chain.
Writing "the polypeptide is shorter" or "the protein is altered" repeats the prompt and scores nothing. The mechanism is the mark.
Mutations can be neutral, beneficial, or harmful.
The effect of a mutation on the organism depends on where it sits in the genome and on what change it produces in the protein. AQA recognises three outcome categories, spanning the spectrum from invisible to catastrophic, with named examples on either end.
The three outcome categories and their credited examples.
| Category | Why no effect, or what effect | Standard example |
|---|---|---|
| Neutral | Falls in a non-coding region, or codes the same amino acid (degenerate code), or alters tertiary structure with no functional consequence | No named disease example |
| Beneficial | Rare; produces a functional advantage | Trichromatic colour vision in humans |
| Harmful | Disrupts protein function, often with serious consequences | Cystic fibrosis (CFTR); sickle cell disease (haemoglobin) |
The two harmful examples both follow the substitution chain from §3.3. A substitution in the CFTR gene alters the chloride channel's tertiary structure and produces the thick mucus characteristic of cystic fibrosis. A single substitution in the haemoglobin beta-globin gene changes one glutamic acid residue to valine; this changes haemoglobin's tertiary structure and produces the sickled red blood cells of sickle cell disease.
Oncogene mutations drive gain-of-function in cell division control.
Oncogenes are mutated versions of proto-oncogenes. The protein product is a signalling protein that normally triggers cell division in response to an external growth signal. The mutation alters the signalling protein in a way that increases its activity, and the cell receives a continuous instruction to divide.
- Mutation changes the base sequence in the proto-oncogene. The tertiary structure of the signalling protein is altered.
- The signalling protein is permanently active, or more signalling protein is produced. The cell receives a "divide" instruction whether or not the external growth signal is present.
- Rapid or uncontrolled cell division follows. The cell cycle runs without its normal regulatory pause.
No
no protein producedand nonon-functional proteinon oncogene stems. The oncogene mechanism is gain of function; the signalling protein is altered or overproduced, never absent.
Write
tertiary structureof the signalling protein. Don't writeactive site; the signalling protein is not an enzyme.
Step two is the discriminator. The protein is present and altered, or it is overproduced. The credited outcome is rapid or uncontrolled cell division. AQA does not credit "growth" or "cell growth" as substitutes anywhere in the topic.
Write
rapidoruncontrolled cell division. AQA rejectsgrowthandcell growthacross the topic.
Tumour suppressor mutations cause loss-of-function through two distinct routes.
Tumour suppressor genes code for proteins that restrain cell division. Loss of tumour suppressor function removes a brake on the cell cycle. Two distinct routes lead to that loss. Both end at rapid or uncontrolled cell division, but the mechanism in the middle differs, and the two must not be mixed in the answer.
The two routes to loss of tumour suppressor function.
| Route | Mechanism in the middle | Why function is lost |
|---|---|---|
| Route one: mutation | Base change alters the amino acid sequence and so the tertiary structure of the regulatory protein | Protein is produced, but its altered fold cannot restrain cell division |
| Route two: methylation | Methyl groups attach to cytosine bases in the promoter region; transcription is suppressed | No mRNA is made, so no regulatory protein is produced |
Keep the two routes separate. AQA grades them as two distinct answer-shapes; mixing the mutation route with the methylation route loses marks on either.
- Mutation changes the base sequence in the tumour suppressor gene. The amino acid sequence, and so the primary structure of the regulatory protein, changes.
- Hydrogen, ionic, or disulfide bonds form differently. The tertiary structure of the regulatory protein is changed.
- The protein can no longer restrain cell division. Rapid or uncontrolled cell division follows.
non-functional proteinis rejected without a structural change. On the mutation route, nametertiary structureand link the altered fold to loss of regulatory function.
No
meiosisin cancer or tumour answers. Tumour cells divide by mitosis; meiosis is rejected wherever it appears in this topic.
Key terms
- mutation
- substitution
- deletion
- addition
- inversion
- translocation
- primary structure
- tertiary structure
- premature stop codon
- signalling protein