IB Biology SLTopic 4 — Making ProteinsPaper 1 & 2Core idea~9 min read
Protein Structure & Mutations
A polypeptide is not much use as a straight chain. It folds into a precise 3D shape, and that shape is what lets it do its job. Change one amino acid and the folding can change — which is how a single wrong base ends up causing a disease.
📘 What you need to know
The base sequence decides the amino acid sequence, which decides how the chain folds, which decides what the protein can do.
A gene mutation is a change in the base sequence of DNA. It may produce a new allele.
Mutations happen randomly and all the time, mostly as copying errors when DNA is replicated in the S phase of interphase.
Most mutations are neutral or harmful, but a few are beneficial.
Only mutations in gametes can be passed on. Mutations in ordinary body cells disappear when those cells die.
A point mutation (base substitution) changes one base. Sickle cell disease is the classic example.
From sequence to shape to job
Follow the chain of cause and effect, because almost every exam answer on this page is built from it:
The chain of consequence
base sequence → amino acid sequence → folded 3D shape → function
Amino acids differ from one another, and those differences pull the chain into a particular shape as it folds. Put a different amino acid in the middle of the chain and it may pull in a different direction, so the finished protein has a different shape. If that protein is an enzyme, its active site may no longer fit the substrate. If it is a transport protein, it may no longer carry what it should.
Whenever a question asks “explain the effect of the mutation”, walk down that arrow chain in your answer. Different base, different amino acid, different folding, different shape, protein cannot do its job. That is usually four marks in one sentence chain.
What a mutation actually is
A gene mutation is simply a change in the sequence of bases in a DNA molecule. Two things about them surprise students:
They are random. Nothing decides that a useful mutation should happen. They mostly arise as copying errors when DNA is being replicated during the S phase of interphase.
They happen constantly. Most do nothing noticeable, either because they fall outside a gene or because the code is degenerate.
Whether a mutation matters to the next generation depends entirely on which cell it happens in:
Where the mutation happens
Passed to offspring?
Why
In a normal body cell (somatic cell)
No
The mutation is lost when those cells die. It can still cause problems in that person, such as a tumour.
In a gamete (egg or sperm)
Yes
The mutated DNA ends up in the zygote, so every cell of the offspring carries it. This is how heritable conditions arise.
Point mutations, and their three outcomes
A point mutation is where a single base in the DNA is swapped for a different one. It is also called a base substitution. What happens next depends on which codon it lands in:
Outcome
What happens to the codon
Effect on the protein
No change
The new codon codes for the same amino acid, because the code is degenerate.
None. The protein is identical.
Different amino acid
The new codon codes for a different amino acid.
Folding may change. Effects range from nothing at all to severe, depending on where in the chain it lands.
Early stop
The new codon is a stop codon.
Translation ends too soon, so the polypeptide is short and almost always non-functional.
Position matters as much as the change. A swapped amino acid buried in a quiet part of the chain often does nothing. The same swap inside an active site or a binding region can wreck the protein completely.
Sickle cell disease: the whole story from one base
Haemoglobin is the protein in red blood cells that carries oxygen. Part of it is a chain called beta-globin. In the gene for beta-globin, one base substitution causes sickle cell disease.
On the coding strand, the DNA triplet GAG becomes GTG.
On the template strand, the triplet CTC becomes CAC.
So the mRNA codon is transcribed as GUG instead of GAG.
GAG codes for glutamic acid; GUG codes for valine. So valine replaces glutamic acid at the sixth position of the chain.
The usual allele is written HbA; the mutated one is HbS.
Every stage after the DNA is just following orders. The mutation only had to happen once, in one triplet.
Why the cells change shape
Valine and glutamic acid behave differently, so swapping them changes how the haemoglobin molecules interact. The faulty haemoglobin (haemoglobin S) tends to stick together in long fibres when oxygen levels are low, and those fibres pull the red blood cell out of its usual round shape into a curved, sickle shape.
Sickled cells carry less oxygen, so tissues get a poorer supply.
They are stiff and awkwardly shaped, so they block capillaries and hold up the normal cells behind them.
People with the condition suffer episodes of severe pain, tiredness and anaemia.
The cells behind the blockage cannot get past either, so a small clump of sickled cells starves a whole patch of tissue of oxygen.
The malaria connection
Sickle cell disease is harmful, so you would expect the allele to be rare everywhere. It is not. It is common in exactly the parts of the world where malaria is common, and that pattern is not a coincidence.
People carrying the HbS allele have more resistance to the malaria parasite. In a region where malaria kills, that advantage outweighs the cost of the allele, so it stays common in the population. It is a neat example of a mutation being harmful in one setting and useful in another.
Worked examples
WORKED EXAMPLE
Follow a substitution through to the amino acid
On the coding strand of the beta-globin gene, the triplet GAG is changed to GTG. Show how this changes the amino acid produced. (GAG codes for glutamic acid, GUG codes for valine.)
Step 1: Write the template strand for eachNormal: CTC Mutated: CACStep 2: Transcribe each into mRNANormal: GAG Mutated: GUGStep 3: Read off the amino acidsGAG = glutamic acid, GUG = valineValine replaces glutamic acidThe middle base is the one that changed, which is why the meaning changed too.
WORKED EXAMPLE
A mutation with no effect
A base substitution changes an mRNA codon from GAA to GAG. Both code for glutamic acid. Explain why this mutation has no effect on the protein.
Step 1: Compare the amino acids
Both codons code for glutamic acid, so the amino acid sequence is unchanged.
Step 2: Follow the chain
Same sequence → same folding → same 3D shape → same function.
Step 3: Name the reason
This is possible because the genetic code is degenerate.
No change to the proteinNotice again that it was the third base that changed. That is usually where harmless swaps happen.
WORKED EXAMPLE
Explain a distribution pattern
Explain why the sickle cell allele is found at high frequency in regions where malaria is common.
The observation
The map of sickle cell alleles closely matches the map of malaria.
The reason
Individuals carrying the HbS allele have greater resistance to the malaria parasite.
The consequence
In those regions they are more likely to survive and reproduce, so the allele is passed on and stays common.
An advantage where malaria is presentSay “correlation” if you are describing the pattern, and keep the survival explanation separate.
💡 Exam tip
Learn the arrow chain — base sequence, amino acid sequence, folding, shape, function. It answers most “explain the effect” questions.
For sickle cell, learn the exact swap: GAG to GTG on the coding strand, GAG to GUG on the mRNA, glutamic acid to valine, at position 6.
Say a mutation is a change in the base sequence, not a change in “the DNA” or “the gene”. Precision earns the mark.
If asked whether a mutation is inherited, check the cell type first: gamete or body cell.
Use the word random when describing how mutations arise. Never write that an organism mutates because it needs to.
A “no effect” answer needs the word degenerate, otherwise it reads like a guess.
⚠ Common mix-up
Thinking every mutation is harmful. Many are neutral, and a few are beneficial. That is where new variation comes from.
Saying the mutation changes the protein directly. It changes the DNA. Everything after that follows from transcription and translation.
Mixing up the coding and template triplets in the sickle cell example. Work out which strand the question has given you before you answer.
Believing all mutations are inherited. Only those in gametes reach the next generation.
Writing that sickle cells “cannot carry oxygen”. They carry less oxygen, which is not the same thing.
Saying sickle cell protects you from malaria completely. It gives increased resistance, not immunity.
Up next: Gene Mutations — the three ways a base sequence can change, what causes them, and why some parts of the genome mutate far more than others.
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