The shape of the lesson
By the end of the lesson, learners can
- Substitution, deletion, insertion: Start on normal, then click substitution, silent substitution, deletion and insertion in turn.
- Why some mutations matter more: The same three types of change have very different effects depending on what they do to the codons.
- Gene mutation = change in DNA base sequence; may alter the polypeptide.
- Substitution changes one codon: same, different or stop.
- Deletion / insertion of one base: frameshift.
- Explain effects via primary structure, folding and function.
One picture every idea returns to
A gene mutation is a change in the sequence of base pairs in a DNA molecule that may result in an altered polypeptide. In a substitution one base pair is replaced by another, so only one codon changes: because the code is degenerate it may still code for the same amino acid (no effect), it may code for a different amino acid (as in sickle cell anaemia, where glutamic acid becomes valine in β-globin), or it may become a stop codon (a shortened polypeptide). A deletion or insertion of one nucleotide causes a frameshift: every codon after the mutation is read differently, so many amino acids change and a stop codon often appears early. The polypeptide usually folds wrongly and cannot function.
Forty-five minutes, phase by phase
| Time | Phase | What happens in the room | Grouping |
|---|---|---|---|
| 0 to 5 min | Hook: predict | Open with the question in the title, One letter wrong, one protein changed.. Copying DNA is accurate but not perfect. Put the figure on the board: it is the one picture every idea in the lesson returns to. | Whole class, then pairs |
| 5 to 17 min | Teach and check: Substitution, deletion, insertion | Start on normal, then click substitution, silent substitution, deletion and insertion in turn. Project tab 7 of the lab (Nucleic acids lab, gene mutations) and let a student drive it while the class predicts. | Whole class, then pairs |
| 17 to 30 min | Teach and check: Why some mutations matter more | The same three types of change have very different effects depending on what they do to the codons. | Mix-Pair-Share |
| 30 to 36 min | Check | The four Stage 1 questions from the student lesson, answered on mini whiteboards or by show of fingers. Re-teach the one most get wrong. | Individual, then whole class |
| 36 to 43 min | Plenary | The exam-style questions from Stage 2, one at a time: thirty seconds alone, then a random call. The feedback lines in the key give the examiner's wording. | Individual, random call |
| 43 to 45 min | Exit and homework | Set the worksheet below (6 questions, 16 marks). Learners self-assess against the objectives before they leave. | Individual |
Protect the parts that carry the learning
The sequence carries about fifty minutes of material, so the lab is driven by one student while the class predicts rather than explored freely. Times are a guide.
Protected: the check at 30 minutes. It is the only individual read on whether the key idea landed, and it is not cut.
Cut first if the build overruns: the last check in Why some mutations matter more, never the check or the plenary.
In a 60 minute block: run worksheet questions 1 to 3 in class as a Rally Coach set and model both the hardest worked example and its check live.
Mix-Pair-Share
Students mix around the room until you call pair; they pair with the nearest classmate, discuss the prompt, then mix again. Three prompts of rising difficulty, three different partners.
The full structure, with its variations and the other twelve, is on the cooperative-learning page.
What to head off, and how
| Trap learners fall into | Teaching move that pre-empts it |
|---|---|
| Do not write that a mutation is a change in an amino acid or in a protein. | A gene mutation is a change in the DNA base sequence; a changed polypeptide is a possible consequence. |
Gene mutations: worksheet
6 questions, 16 marks. Written in the style of the papers; no past paper question is reproduced.
State what is meant by a gene mutation and name the three types described in your syllabus.
Explain how a single base substitution in the β-globin gene leads to sickle cell anaemia.
The mRNA for the start of a polypeptide reads AUG GCU AAA GGC UGG. (AUG Met, GCU Ala, AAA Lys, GGC Gly, UGG Trp, GCA Ala, AAG Lys, GCU Ala, AAG Lys, UAA stop.) The first A of the third codon is deleted. Write the new codon sequence and amino acid sequence, and name the type of effect.
Explain why some substitutions have no effect on the polypeptide, whereas others make it non-functional.
An insertion of one nucleotide occurs in the last codon before the stop codon of a gene. Suggest why this may have little effect on the protein.
Suggest why deleting three adjacent nucleotides usually has a smaller effect than deleting one nucleotide.
Answer key and marking notes
- A change in the sequence of base pairs in a DNA molecule (which may result in an altered polypeptide).
- Substitution, deletion and insertion (of nucleotides).
- The substitution changes one triplet in the DNA, CTC to CAC on the template strand, so the mRNA codon changes from GAG to GUG.
- Glutamic acid is replaced by valine in the β-globin polypeptide.
- Valine is non-polar/hydrophobic whereas glutamic acid is charged, so the haemoglobin molecules stick together at low oxygen concentrations.
- This forms long fibres that distort the red blood cells into a sickle shape, so they carry less oxygen and can block capillaries.
- New mRNA: AUG GCU AAG GCU GG...
- Amino acids: Met-Ala-Lys-Ala-...
- A frameshift: every codon after the deletion is read in a different frame (here the first changed codon still codes for Lys, but those after it differ).
- The genetic code is degenerate, so the new codon may code for the same amino acid; then the polypeptide is unchanged.
- If a different amino acid is coded, the primary structure changes, which can change bonding, folding and the tertiary structure (for example of an active site), so function is lost.
- If the new codon is a stop codon, the polypeptide is shortened and usually non-functional.
- Only the reading frame from that point onwards changes, and all earlier codons are read normally, so almost all of the primary structure is unchanged.
- The changed or extra amino acids (before a new stop codon is reached) are at the very end of the chain, which may not affect folding or the active site.
- Deleting three nucleotides removes one codon, so one amino acid is lost (or one changed), and the reading frame is kept.
- Deleting one nucleotide causes a frameshift, changing every codon after it.
8 multiple-choice questions on this lesson
From the topic question bank. Assign them in the app for a marked score in your gradebook, or run the topic as a class game.
Which of these is a gene mutation?
- Athe base pair C-G at one position in a gene is replaced by T-A
- Ban extra chromosome 21 is present in each body cell
- Can mRNA molecule is broken down after it has been translated
- Da polypeptide folds incorrectly because the temperature is too high
The diagram shows part of a normal mRNA and the same part from two mutant alleles. Which describes mutant P?
- Aa substitution that creates a stop codon, giving a shorter polypeptide
- Ba substitution that changes tyrosine to a different amino acid
- Ca deletion that shifts the reading frame from the fourth codon
- Da substitution with no effect, because the code is degenerate
Which type of gene mutation changes only one codon and never causes a frameshift?
- Asubstitution of one nucleotide
- Bdeletion of one nucleotide
- Cinsertion of one nucleotide
- Dinsertion of two nucleotides
In sickle cell anaemia, a substitution changes the mRNA codon GAG to GUG. What is the effect on the β-globin polypeptide?
- Aone glutamic acid is replaced by valine; the rest is unchanged
- Bevery amino acid after the mutation is changed
- Cthe polypeptide is shortened by an early stop codon
- Dthe polypeptide is unchanged because the code is degenerate
Why does a single base substitution sometimes have no effect on the polypeptide?
- Amore than one codon can code for the same amino acid
- Bthe ribosome can correct a wrong base during translation
- CtRNA molecules ignore the third base of every codon
- Dsubstitutions only ever happen in non-coding DNA
Mutation A deletes one nucleotide in codon 5 of a 400-codon gene. Mutation B deletes one nucleotide in codon 395. Which mutation is more likely to make the protein non-functional, and why?
- AA, because the frameshift changes almost every amino acid in the chain
- BB, because mutations near the stop codon prevent translation ending
- CA, because it removes the start codon so no protein is made
- Dboth equally, because any deletion has the same effect
An enzyme has one amino acid substituted. In mutant 1 the change is in the active site; in mutant 2 it is on the outer surface, far from the active site, and replaces one hydrophilic amino acid with another hydrophilic one. Which prediction is most likely?
- Amutant 1 loses activity; mutant 2 keeps most of its activity
- Bmutant 2 loses activity; mutant 1 keeps most of its activity
- Cboth lose all activity, because the primary structure has changed
- Dneither changes, because only one amino acid is different
A gene codes for a polypeptide of 146 amino acids. An insertion of three nucleotides occurs between two codons in the middle of the gene, and creates no stop codon. How many amino acids does the new polypeptide contain?
- A147
- B146
- C149
- D145
Quiz key
Replacing one base pair with another changes the base sequence of the DNA: a substitution, which is a gene mutation. An extra chromosome is a change in chromosome number, not in the base sequence of a gene. Breaking down mRNA is normal control of gene expression. A protein denatured by heat has unchanged DNA.
UAC (tyrosine) has become UAA, a stop codon, so translation ends after Met-Pro-Glu and the polypeptide is shortened. No amino acid replaces tyrosine; the chain simply stops. The number of bases is unchanged, so it is not a deletion. The meaning has changed completely, so the change is not silent; that describes mutant Q, where GGA and GGG both code for glycine.
A substitution swaps one base for another, so the number of bases and the reading frame stay the same and only one codon can change. Deleting or inserting one or two nucleotides moves every following base into a new triplet, causing a frameshift.
Only the one codon changes, from glutamic acid (GAG) to valine (GUG); every other amino acid is normal. Changing every later amino acid would need a frameshift from a deletion or insertion. GUG is not a stop codon. GAG and GUG code for different amino acids, so the change is not silent.
The genetic code is degenerate: most amino acids have several codons, so the new codon may still code for the same amino acid. Ribosomes do not correct bases in the mRNA. tRNAs do pair with all three bases, though the third base is often the one that varies between codons for the same amino acid. Substitutions can occur anywhere, including in exons.
A frameshift alters every codon downstream, so a deletion at codon 5 changes almost the whole primary structure (and often brings in an early stop codon), while one at codon 395 changes only the last few amino acids. B does not stop translation from ending; at most it changes or shifts the stop position at the very end. Codon 5 is not the start codon (codon 1). The position of a deletion makes a big difference.
A change in the active site can alter its shape or charge so the substrate no longer binds, so activity falls. A similar amino acid on the surface is unlikely to change folding or the active site. Mutant 2 is the less damaging one, not the more damaging. A change in primary structure does not always destroy function: it depends on where it is and how different the R groups are. One amino acid can matter a great deal, as in sickle cell haemoglobin.
Three extra nucleotides between codons add one whole codon without shifting the reading frame, so the polypeptide has one extra amino acid: 147. 146 ignores the inserted codon. 149 counts each inserted nucleotide as an amino acid. 145 treats the change as a deletion.
What to project
The student lesson embeds these tabs. Open them full screen on the projector; every slider has a drag handle on the stage.
Slides for this lesson
A projectable deck for every pack is on the way. Until then, present the student lesson full screen: its sections, figure and lab tabs follow the same order as the plan above.