How Mutations Affect Proteins

What this lesson covers in the specification

Incandio is aligned to this specification. It is not published by, endorsed by or affiliated with Pearson, and it reproduces none of Pearson's wording — the statement numbers are given so you can check every lesson against your own copy.

• 3.35 — How a change in DNA can alter the amino acid sequence of a protein and so the phenotype (bold B statement — Paper 2 only)
• 3.36 — Most mutations have no effect; some have a small effect; rarely a significant one (bold B statement — Paper 2 only)
• 3.37 — How ionising radiation and chemical mutagens increase the incidence of mutation (bold B statement — Paper 2 only)

1 · Understand it

No exam language yet. The only question this section answers is: do I actually understand what is happening?

You already have the chain: the order of bases determines the order of amino acids, the order of amino acids determines the shape the protein folds into, and the shape determines what the protein does. A mutation is a change at the first link, so the question this page answers is how far along that chain the change actually travels — and the honest answer is that usually it does not travel at all.

The chain, run in the damaged case

1. A base in the DNA of a gene is changed, added or removed.
2. The mRNA transcribed from that gene therefore carries a changed codon.
3. That codon may specify a DIFFERENT amino acid, so a different amino acid is placed at that position in the chain.
4. A different amino acid may cause the chain to fold into a different SHAPE.
5. A different shape may mean the protein no longer works as it should — an enzyme whose active site no longer fits its substrate, for example.
6. If that protein was responsible for a characteristic, the PHENOTYPE changes.

Notice how many of those steps say MAY. That is not hedging; it is the content of statement 3.36, and each 'may' is a place where the consequences can stop dead. Most mutations have NO EFFECT at all, some have a SMALL effect, and only rarely does one significantly change the phenotype.

Why a mutation so often does nothing — the four places the chain can stop

1. MOST OF THE GENOME IS NOT A GENE. A change in a stretch of DNA that does not code for a protein usually changes nothing at all.
2. THE CODE HAS SPARES. There are 64 possible codons and only 20 amino acids, so several different codons specify the same amino acid. A change from one to another leaves the protein completely unaltered.
3. SOME AMINO ACIDS DO NOT MATTER MUCH. A different amino acid at a position far from the active site of an enzyme may leave the shape that matters unchanged, giving a protein that still works — perhaps slightly less well, which is the 'small effect' case.
4. THE OTHER ALLELE MAY COVER IT. In a diploid organism there are two copies of every gene. If the mutated allele is recessive, the working allele on the other chromosome is expressed and the phenotype is unchanged.

Think of it like a typo in a long document

Most typos land in a page nobody reads, or produce a word the reader corrects without noticing, or change 'colour' to 'color' — a real difference that changes nothing about the meaning. A few make a sentence slightly awkward. Very occasionally one lands on a number in a critical instruction and the whole thing is ruined. And once in a very long while a typo produces a phrase that is genuinely better than what was written. Those proportions are roughly right for mutations, and they explain why evolution is slow: the useful ones are rare, but they accumulate because they are the ones that persist.

When a mutation does have a significant effect, the mechanism is usually the same one. Most proteins that matter are enzymes, and an enzyme works because its active site has a shape complementary to its substrate. Change one amino acid in or near the active site and the shape changes; change the shape and the substrate no longer fits; and an enzyme that cannot bind its substrate cannot catalyse its reaction. That is the causal chain to write out whenever a question asks how a mutation causes a condition.

Because mutations are random, they are also usually harmful when they have any effect at all — for the same reason that a random change to a working machine is more likely to break it than improve it. But 'usually harmful' is not 'always', and a rare beneficial mutation is where every adaptation ultimately came from. A mutation that produces an enzyme working slightly better at a lower temperature, or a bacterial protein that an antibiotic can no longer bind to, is not different in kind from a harmful one — only in its consequences for the organism carrying it.

What increases the rate of mutation

1. IONISING RADIATION — gamma rays, X-rays and ultraviolet light. These carry enough energy to damage DNA directly, breaking bonds and altering bases. The greater the dose, the higher the rate of mutation.
2. CHEMICAL MUTAGENS — substances such as those in tobacco smoke, which react with DNA and change its structure.
3. Both act by increasing the CHANCE that a mutation occurs. They do not decide which mutation occurs, and they do not direct it towards anything useful — the randomness is unaffected.
4. A mutagen that causes mutations leading to uncontrolled cell division is described as a CARCINOGEN, because uncontrolled division of cells is what a cancer is.

One point about dose that is worth understanding rather than memorising. Mutations occur at a low rate anyway, without any mutagen present — from ordinary errors when DNA is copied and from natural background radiation. A mutagen raises that rate; it does not create the phenomenon. That is why exposure is discussed in terms of increased RISK rather than certain harm, and why the risk rises with the dose received and the time spent exposed.

2 · Grade 9 Notes

A different job from the section above. You have already understood it; this is the precise set of things to LEARN — definitions to reproduce word for word, processes in order, equations with units, and the answers that score full marks.

Learn this definition · Mutagen

An agent that increases the rate at which mutations occur — such as ionising radiation or a chemical mutagen. It raises the probability of a mutation but does not determine which mutation occurs.

Learn this definition · Carcinogen

A mutagen that causes mutations leading to uncontrolled cell division, and so increases the risk of cancer.

Why the same exposure gives different outcomes in different people

• A mutagen changes the RATE of mutation, not which mutation occurs or where in the DNA
• Only mutations in the particular genes controlling cell division can lead to a tumour — one of an enormous number of possible outcomes
• So the same dose produces different mutations, and therefore different outcomes, in different individuals
• Risk rises with dose and with time of exposure; it is never a certainty for any one person
• Mutations also occur without any mutagen, from copying errors and background radiation — which is why no single case can prove what caused it, and why the evidence is drawn from large populations

Statement 3.35 — from a changed base to a changed phenotype, the chain to write

1. A base in the DNA of a gene is changed, added or removed.
2. The mRNA transcribed from the gene therefore carries a changed codon.
3. A different amino acid may be placed at that position in the chain.
4. The chain may then fold into a different shape.
5. The protein may no longer function — for an enzyme, the active site no longer fits the substrate.
6. If that protein is responsible for a characteristic, the phenotype changes.

Statement 3.36 — why most mutations have no effect

Most DNA is not a gene

A change in a non-coding stretch usually alters no protein at all.

The code has spares

There are 64 codons for 20 amino acids, so several codons specify the same amino acid — a change between them alters nothing.

Position matters

An amino acid changed far from an enzyme's active site may leave the working shape unchanged, or affect it only slightly.

The other allele

In a diploid organism, a recessive mutated allele is masked by a working dominant allele on the other chromosome.

The rare case

A mutation in a critical position of a gene for an important protein can change the phenotype significantly, which is why the effects range from none to severe.

Statement 3.37 — mutagens, and exactly what they do

• IONISING RADIATION — gamma rays, X-rays and ultraviolet light, which carry enough energy to damage DNA directly
• CHEMICAL MUTAGENS — including substances in tobacco smoke, which react with DNA and alter its structure
• Both INCREASE THE RATE at which mutations occur; neither determines which mutation occurs
• The risk increases with the DOSE received and the TIME of exposure
• Mutations occur at a low rate anyway, from copying errors and background radiation — a mutagen raises that rate rather than creating the phenomenon
• A mutagen causing mutations that lead to uncontrolled cell division is called a CARCINOGEN

What a mutagen does and does not do

A. IT DOES increase the probability that a mutation occurs somewhere in the DNA, with the risk rising as the dose and exposure time rise.

B. IT DOES NOT determine which mutation occurs, or direct it towards anything useful. Mutations remain random whether or not a mutagen is present.

Why harmful mutations outnumber beneficial ones

A. A protein's function depends on a precise shape, and a random change is far more likely to disrupt a working arrangement than to improve it.

B. But beneficial mutations do occur, and they are the origin of every adaptation — they persist because organisms carrying them survive and reproduce more successfully.

Not this: A mutation will change an organism's characteristics.

This: Most mutations change nothing observable — the DNA may not be in a gene, the codon may specify the same amino acid, the position may not matter, or a working allele may mask it.

Model answer [5 marks]

Explain how a change in one base of a gene can result in a non-functioning enzyme. [5]

The changed base means the mRNA transcribed from the gene carries a different codon. That codon may specify a different amino acid, so a different amino acid is placed at that position in the chain. The chain then folds into a different shape. If the change is in or near the active site, the shape of the active site is altered so that the substrate no longer fits it. The enzyme can therefore no longer bind its substrate and cannot catalyse its reaction.

Model answer [4 marks]

Explain why most mutations have no effect on the phenotype. [4]

Most of an organism's DNA does not code for a protein, so a change there alters nothing. Even within a gene, several different codons code for the same amino acid, so a change may leave the amino acid sequence unaltered. If a different amino acid is placed at a position away from the active site, the protein may still fold into a working shape. And in a diploid organism a recessive mutated allele may be masked by a working dominant allele on the other chromosome.

Model answer [3 marks]

Explain how exposure to ionising radiation increases the risk of cancer. [3]

Ionising radiation carries enough energy to damage DNA directly, so it increases the rate at which mutations occur, and the risk rises with the dose received and the time of exposure. If a mutation occurs in a gene controlling cell division, that control may be lost. Uncontrolled cell division is what forms a tumour, so the risk of cancer is increased.

Mark-losing trap. Most mutations have NO effect. Never begin an answer by assuming a mutation changes something.

Mark-losing trap. Write the whole chain: base → codon → amino acid → shape → function → phenotype. Each link is a mark.

Mark-losing trap. A mutagen increases the RATE of mutation. It does not choose which mutation happens.

Mark-losing trap. For an enzyme, say the ACTIVE SITE changes shape so the SUBSTRATE no longer fits. 'The enzyme is damaged' is too vague.

Mark-losing trap. Mutations are random, so they are usually harmful — but 'usually' is not 'always', and beneficial ones are where adaptations come from.

3 · Prove it — the five questions

The five questions climb Grade 6 → Grade 7 → Grade 8 → Grade 9 → Grade 9 challenge, and are marked inside Incandio on your own device, by rule, with an authored diagnosis of the mistake you actually made. The mark schemes stay in the app so that the practice is worth doing; the questions themselves are here.

1. Grade 6 · State [1 mark] — Which of these is an example of ionising radiation, which can increase the rate of mutation?
2. Grade 7 · Explain [2 marks] — A mutation changes one base in a gene, but the protein produced is completely unchanged. Explain how this is possible.
3. Grade 8 · Explain [5 marks] — A mutation changes one base in the gene coding for an enzyme, and the enzyme produced can no longer catalyse its reaction. Explain how the change in one base has this effect. Select every statement that belongs in a full-mark explanation.
4. Grade 9 · Calculate [3 marks] — A gene is 1500 bases long. A mutation changes a single base at random, anywhere within it. Given that several codons code for the same amino acid, a change at 300 of the 1500 base positions would leave the amino acid sequence unaltered. Calculate the percentage of base positions at which a single-base change would leave the amino acid sequence unchanged.
5. 9+ · Analyse [5 marks] — Two people are exposed to the same dose of ionising radiation. One develops a tumour some years later; the other is unaffected. A student says this shows that the radiation could not have caused the tumour, since the same exposure did not cause one in both people. Select every statement that belongs in a full-mark evaluation.

The people behind this science

Two ways into the same idea — the one who isolated the mutagen and paid for it, and the one who warned what a beneficial mutation would do. Inside Incandio each of them answers knowing exactly which lesson you have just finished.

Marie Curie — the one who isolated the mutagen and paid for it

Statement 3.37 names ionising radiation as a cause of mutation, and Curie isolated the substances that emit it. She and Pierre described the burns their samples produced on skin, and she worked with radium for decades with no protection — carrying tubes of it in her pockets and keeping it beside her bed because it glowed. She died in 1934 of a blood disorder consistent with prolonged exposure, and her laboratory notebooks are still radioactive enough to be kept in lead-lined boxes. She also drove mobile X-ray units to the front in the First World War, which saved lives using the same phenomenon.

• “What did you notice radium doing to skin?”
• “How could something invisible damage living tissue?”
• “Did you know the risk at the time, and would it have changed anything?”
• “Why did you take X-ray units to the battlefield?”
• “What is it like to discover something that is both useful and dangerous?”

Alexander Fleming — the one who warned what a beneficial mutation would do

The rare beneficial mutation described on this page is not an abstraction, and Fleming saw the consequence coming before anyone else. In his 1945 Nobel lecture he warned that bacteria exposed to too little penicillin would become resistant to it, and that a careless person could pass a resistant strain to someone else. He was describing exactly what this page sets up: a random mutation producing a protein an antibiotic cannot bind to, in an organism reproducing fast enough for the rare to become common. The next lesson is what happened next.

• “Why did you think bacteria would become resistant to penicillin?”
• “What does an underdose actually do to a population of bacteria?”
• “How can a change that is rare become common so quickly?”
• “Were you surprised how soon your warning came true?”

Carry on through the course

• Previous lesson: Variation and Mutation
• Next lesson: Natural Selection and Antibiotic Resistance
• Sexual and Asexual Reproduction — Two ways to make a new organism — one produces copies, the other produces something that has never existed before. Why any species would want both.
• Flowers, Pollination and Fertilisation — Two completely different solutions to one problem — a plant that cannot move has to get its male gamete to another plant's female gamete.
• Seeds and Germination — What a seed needs to start growing, what it lives on before it has a single leaf — and why light is not on the list.
• The Human Reproductive Systems — Two systems built around the same problem — making gametes and bringing them together — and the hormones that switch them on.
• The Menstrual Cycle — Four hormones, two organs and one repeating question — should the uterus lining be built up, held, or let go?
• All of Biology · Biology key terms · required practicals · Incandio Science · The 4BI1 specification