Alteration of the sequence of bases in DNA can alter the
AQA
A-Level
A gene mutation is a change in the base sequence of DNA. These might arise spontaneously during DNA replication, for example if DNA polymerase inserts an incorrect nucleotide, producing a substitution. Other types arise through different errors: deletion removes a base and addition inserts one; unless the number changed is a multiple of three, this causes a frameshift, altering every subsequent triplet. Duplication repeats a section of bases. Inversion reverses a sequence of bases so its triplets are read backwards. Translocation moves a sequence of bases to a different position within the DNA sequence. These changes can alter the mRNA codons, potentially changing the amino acid sequence and the protein's tertiary structure.
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Objectives
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Exam Tips
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Pitfalls
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Key Terms
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Mark Points
Subtopics in this area
Gene mutations might arise during DNA replication. They include addition, deletion, substitution, inversion, duplication and translocation of bases.
Gene mutations occur spontaneously.
The mutation rate is increased by mutagenic agents.
Mutations can result in a different amino acid sequence in the encoded polypeptide.
Some gene mutations change only one triplet code.
Due to the degenerate nature of the genetic code, not all such mutations result in a change to the encoded amino acid.
Some gene mutations change the nature of all base triplets downstream from the mutation, ie result in a frame shift.
Students should be able to relate the nature of a gene mutation to its effect on the encoded polypeptide.
Alteration of the sequence of bases in DNA can alter the Revision Guide
Learning Objectives
What you need to know and understand
- Name six types of gene mutation and describe what each does to the base sequence.
- Explain why a mutation arising during DNA replication is passed on to daughter cells.
- Predict the effect of a given mutation on the encoded polypeptide, using the terms triplet, codon and amino acid sequence.
- State what is meant by a spontaneous mutation and give its main cause in a dividing cell.
- Explain why a resistance allele must already exist in a population before the selection pressure is applied.
- Write a natural selection explanation in the correct order, using allele rather than gene and frequency rather than number.
- Name three mutagenic agents and describe the mechanism by which each raises the mutation rate.
- Explain why a mutagen increases the number of mutations without determining which gene mutates.
- Distinguish the consequences of a mutagen-induced mutation in a somatic cell from one in a cell that forms gametes.
- Explain how a change to one DNA triplet alters the amino acid sequence of the polypeptide produced.
- Explain how a changed amino acid alters the tertiary structure of a protein, referring to R group interactions.
- Predict the effect on enzyme activity of a substitution affecting the active site, using complementary shape and enzyme-substrate complexes.
- Explain why a base substitution changes only one triplet, referring to the non-overlapping triplet code.
- Predict, from the new triplet a substitution creates, whether the polypeptide has one amino acid changed, no change at all, or is shortened at a premature stop triplet.
- Explain why a mutation affecting one triplet can have effects ranging from none to a completely non-functional protein.
- Explain, using the number of triplets and the number of amino acids, why the genetic code must be degenerate.
- Explain why a base substitution may produce no change at all in the encoded polypeptide.
- Select the correct property of the genetic code, degenerate, non-overlapping or universal, for a given exam context.
- Explain why the addition or deletion of one base causes a frame shift while a substitution does not.
- Rewrite a given base sequence in codons after an insertion to show which codons change.
- Explain why a frame shift near the start of a gene usually has a greater effect than one near the end.
- Identify the type of mutation from two given DNA sequences and state how many triplets are affected.
- Predict the effect of a given mutation on the length and the amino acid sequence of the polypeptide.
- Justify why two different mutations in the same gene can have very different effects on the protein.
Marking Points
Key points examiners look for in your answers
- Define a gene mutation as a change in the base sequence of DNA.
- State that gene mutations might arise spontaneously during DNA replication.
- Describe the specific mechanism of a named mutation type, such as substitution, addition, deletion, duplication, inversion, or translocation of bases.
- Explain that a mutation can change the sequence of amino acids in the encoded polypeptide.
- Explain that an altered amino acid sequence can change the position of hydrogen, ionic, and disulfide bonds, altering the protein's tertiary structure.
- State that mutations occur at random or by chance, primarily as errors during DNA replication.
- Establish that the mutation occurs before, and independently of, any environmental selection pressure.
- Identify that the mutation produces a new allele, creating genetic variation within the population.
- Explain that selection pressures act on existing variation, increasing the survival and reproductive success of individuals with the advantageous allele.
- Conclude that the frequency of the advantageous allele increases over many generations.
- Define a mutagenic agent as a factor that increases the rate of mutation above the natural or spontaneous rate.
- Identify forms of ionising radiation (e.g., X-rays, gamma rays) or ultraviolet light as physical mutagens.
- Describe the action of a chemical mutagen, such as a base analogue being incorporated into DNA and pairing incorrectly.
- Clarify that while mutagens increase the frequency of mutations, the specific mutations produced remain random in type and position.
- Link an increased mutation rate in somatic cells to an increased risk of cancer via mutations in tumour suppressor genes or proto-oncogenes.
- A change in the DNA base sequence changes the mRNA codon.
- A different tRNA anticodon brings a different amino acid, altering the primary structure.
- Different R group interactions (such as ionic or disulfide bonds) change the tertiary structure.
- The active site is no longer complementary, so fewer enzyme-substrate complexes form.
- An altered signalling protein can cause rapid, uncontrollable cell division in tumours.
- one mark for stating that the code is non-overlapping and read in triplets, so a substitution affects only one triplet
- one mark for stating that the reading frame and all other triplets are unchanged
- one mark for only one amino acid in the polypeptide being changed, provided the new triplet is not a stop triplet
- one mark for the effect ranging from none, because the code is degenerate, to a non-functional protein where the amino acid is at a critical position
- one mark for a correct named example, such as a substitution causing sickle cell anaemia
- one mark for more than one triplet or codon coding for the same amino acid
- one mark for the substituted triplet still coding for the same amino acid
- one mark for no change to the amino acid sequence of the polypeptide, so no change to its tertiary structure or function
- one mark for stating that a substitution in the third base of a triplet is the most likely to be silent
- one mark for distinguishing degenerate from universal, where a question about expressing a gene in another species requires universal
- An addition or deletion of a base shifts the reading frame.
- All codons downstream of the mutation are changed.
- A completely different sequence of amino acids from the point of the mutation onwards.
- The polypeptide is non-functional because its tertiary structure is altered, or a premature stop codon produces a shortened polypeptide.
- A frame shift near the start of a gene has a greater effect than one near the end.
- Use codon for mRNA triplets and triplet for DNA base triplets.
- One mark for identifying the type of mutation from a given sequence or description, for example substitution, addition or deletion.
- One mark for stating whether the reading frame is shifted, and therefore how many triplets are affected; a substitution or a multiple-of-three addition or deletion preserves the frame, whereas a non-multiple-of-three addition or deletion shifts it.
- One mark for using the degeneracy of the code where the amino acid is unchanged, for example a substitution producing a triplet that still codes for the same amino acid.
- One mark for linking a changed amino acid to altered R group interactions and a changed tertiary structure.
- One mark for a correct statement about function, such as no enzyme-substrate complexes forming, or a truncated polypeptide from a premature stop codon.
Examiner Tips
Expert advice for maximising your marks
- 💡Open any mutation explanation by stating it is a 'change in the base sequence of DNA'.
- 💡If asked to describe a named mutation, state the type and explicitly describe its effect on the DNA triplets (e.g., causing a frameshift).
- 💡Always refer to a change in the 'sequence of amino acids' or 'primary structure' rather than just saying it makes a different protein.
- 💡Write natural selection answers in a fixed chronological order: mutation, new allele, survival advantage, reproduce and pass on the allele, allele frequency increases over generations.
- 💡Never let the selection pressure appear before the mutation in your sentence order.
- 💡Explicitly state 'over many generations' when describing a change in allele frequency.
- 💡When explaining how a mutagen increases the mutation rate, focus on the base-level mechanism: incorrect pairing, broken strands, or inserted bases.
- 💡Distinguish somatic mutations from gamete mutations whenever a question mentions inheritance or offspring.
- 💡If the stem introduces an unfamiliar chemical mutagen, describe the mechanism provided in the text rather than naming a learned chemical.
- 💡Detail the full sequence: base sequence, codon, amino acid sequence, R group interactions, tertiary structure, then function.
- 💡Explicitly write 'tertiary structure', as examiners often ignore '3D structure' on its own.
- 💡State explicitly which mutations preserve the reading frame: substitution, and additions or deletions of three bases.
- 💡Keep the vocabulary separate, using triplet for DNA, codon for mRNA and anticodon for tRNA.
- 💡Give sickle cell anaemia as your named example, since it is the standard single-substitution case.
- 💡Learn the three properties of the code as a set, each with a typical question, so you pick the right one under pressure.
- 💡If asked why a mutation had no effect on the protein, name degeneracy and say the new triplet codes for the same amino acid.
- 💡Count triplets and amino acids in your answer: 64 against 20 is a quick, creditable justification.
- 💡Count the bases added or deleted: if the number divides by three, there is no frame shift.
- 💡When given a sequence, rewrite it in codons after the mutation so the examiner can see the new reading frame.
- 💡Say how many amino acids are affected rather than just saying the protein changes.
- 💡Work the sequence through in triplets on the paper; examiners credit correct working even when the final statement is incomplete.
- 💡Quantify the change: say one amino acid changed, or all amino acids after position 12 changed.
- 💡Name the mutation type first, then the effect; the two are usually separate marks.
Common Mistakes
Pitfalls to avoid in your exam answers
- Writing that 'different amino acids are formed'; correction: state that a different amino acid is inserted, which changes the overall sequence or order of amino acids in the polypeptide.
- Confusing a gene mutation with a chromosome mutation; correction: gene mutations involve changes to the DNA base sequence, whereas chromosome mutations involve changes in chromosome number or structure, such as deletion, duplication, inversion or translocation of chromosome segments.
- Describing an inversion as a loss of bases; correction: state that the bases are still present but their sequence is reversed.
- Writing that an antibiotic, pesticide or pathogen caused the mutation; the mutation is spontaneous and pre-existing.
- Stating that organisms mutate to adapt or because they need to, which implies purposeful change rather than random mutation.
- Using the term 'gene' where 'allele' is required to describe the new genetic variant.
- Saying the 'number' of alleles increases rather than the 'frequency' or 'proportion' of the allele.
- Assuming mutation only happens when a mutagen is present, ignoring the natural spontaneous mutation rate.
- Stating that a mutagen causes one specific, targeted mutation, rather than raising the probability of random changes.
- Using 'mutagen' and 'carcinogen' interchangeably without explaining the link through tumour suppressor genes or proto-oncogenes.
- Saying ultraviolet light 'burns' the DNA rather than describing the formation of thymine dimers or a distorted strand.
- Claiming every mutagen-induced mutation is inherited; only mutations in gamete-forming cells can be passed to offspring.
- Stating that 'different amino acids are formed' instead of 'a different sequence of amino acids is produced'.
- Claiming the primary structure is unchanged while the tertiary structure changes; a changed amino acid sequence is a changed primary structure.
- Saying the enzyme is 'denatured' by a mutation; denaturation describes the effect of heat or extreme pH, not genetic changes.
- assuming any single-base change alters the whole polypeptide, which is true of a frame shift but not of a substitution
- describing a deletion of one base as changing only one triplet
- saying the code is universal when the point required is that it is non-overlapping or degenerate, a confusion mark schemes penalise
- claiming a single amino acid change can never matter
- mixing up triplet on DNA, codon on mRNA and anticodon on tRNA
- answering why bacteria can make a human protein with the code is degenerate, which mark schemes explicitly reject; the required point is that the code is universal
- claiming degeneracy means one triplet can code for several amino acids, which reverses the definition
- assuming every substitution is silent
- thinking a silent mutation means no mutation happened, when the DNA base sequence has genuinely changed
- using codon for the DNA triplet when the question refers to DNA
- Writing that the whole polypeptide is changed, when only the part downstream of the mutation is affected. Correction: specify that only codons after the mutation are altered.
- Believing every deletion causes a frame shift, forgetting that a deletion of three bases does not. Correction: only insertions or deletions not in multiples of three cause a frame shift.
- Omitting the word downstream, so the answer never identifies which codons change. Correction: state that all codons downstream of the mutation are affected.
- Describing a substitution as causing a frame shift. Correction: a substitution changes one codon and does not shift the reading frame.
- Saying the protein is denatured rather than that a different polypeptide has been made. Correction: a frame shift produces a different amino acid sequence, not a denatured version of the original.
- Jumping straight to the protein without first identifying the type of mutation. Correction: name the mutation type first, then work out its effect.
- Assuming every mutation is harmful, when silent and neutral mutations are common. Correction: check whether the amino acid sequence actually changes before claiming an effect.
- Comparing two DNA sequences base by base and missing that an insertion has shifted everything along. Correction: align the sequences in triplets from the start of the gene.
- Forgetting to check whether a new stop triplet has been created. Correction: scan the new sequence for stop triplets, as these truncate the polypeptide.
- Writing about the effect on the gene when the question asked about the polypeptide. Correction: answer in terms of amino acid sequence, tertiary structure and protein function.