D1.3 Mutation and gene editing
Mutation and gene editing explain how DNA sequence changes arise, affect proteins, create variation and can be studied or altered deliberately.
- Syllabus
- First assessment 2025
- Topic
- D1.3
- Level
- SL
A Gene Mutation Changes a DNA Sequence
A gene mutation is a structural change in the base sequence of DNA within a gene.
| Mutation | Sequence change |
|---|---|
| Substitution | One base is replaced by another |
| Insertion | One or more bases are added |
| Deletion | One or more bases are removed |
| Duplication | A DNA section is copied, producing an extra copy |
Changing 5′-ACT-3′ to 5′-AGT-3′ is a substitution; changing it to 5′-ACCT-3′ is an insertion.
A mutation is the DNA sequence change itself. Its effect on a codon, protein or phenotype is a possible consequence, not part of the definition.
Gene mutations
Assessment in practice
1 marksHow it is assessed
This objective is assessed through structured response, commonly using Define / Identify / Distinguish.
Command terms
Define / Identify / Distinguish / Compare
What earns marks
Build the answer around this relationship: Gene mutations are changes in DNA nucleotide sequence.
Watch for
Naming a disease such as sickle-cell anemia instead of naming a mutation type.
Representative question
Question 1
[Maximum number: 2]
Mutations may increase variation within a species. Compare and contrast substitution and insertion mutations.
Similarity:
a. both involve changes in the sequence of DNA/bases/nucleotides/triplets
OR
both may cause the production of a different amino acid/protein/polypeptide;
Difference:
b. substitution changes a base/nucleotide while insertion adds a base/nucleotide
OR
substitution changes one triplet while insertion changes more / causes frameshift
OR
substitution may not change protein/polypeptide function while insertion usually does;
Marking guidance:
Accept codon in place of triplet.
b. the contrast between substitution and insertion must be clear.
2
max
A Base Substitution Can Be Silent, Missense or Nonsense
A single-nucleotide polymorphism (SNP) results from a base substitution, but the substitution may or may not change one amino acid in a polypeptide.
| Codon outcome | Polypeptide consequence |
|---|---|
| Silent | The new codon specifies the same amino acid because the code is degenerate |
| Missense | The new codon specifies a different amino acid |
| Nonsense | The new codon is a stop codon, so translation ends early |
An mRNA codon change from GAA to GAG is silent because both specify glutamate; a change to a stop codon can shorten the polypeptide.
A substitution does not automatically change protein function. First identify the new codon and its amino-acid or stop outcome.
Base substitution consequences
Assessment in practice
1–4 marksHow it is assessed
This objective is assessed through structured response, multiple choice, commonly using Describe / Explain / Outline.
Command terms
Describe / Explain / Outline
What earns marks
Build the answer around this relationship: A substitution changes one base in a DNA sequence.
Watch for
Stopping at the DNA substitution without tracing the codon and amino acid consequence.
Representative question
Question 1
[Maximum number: 4]
Outline how a base substitution leads to sickle cell anemia.
a. substitution occurs in one base of a DNA triplet
OR
GAG is replaced by GTG;
b. mRNA is transcribed with the incorrect triplet/codon;
c. CAC instead of CUC;
d. a different amino acid is translated/ glutamic acid is replaced by valine;
e. altering a peptide/amino acid sequence in hemoglobin;
f. changes the shape of red blood cells / blood cells adopt a sickle shape OR
red cells carry less oxygen;
4 max
Insertions and Deletions Can Shift the Reading Frame
Insertions and deletions are likely to stop a polypeptide functioning when they shift its reading frame or change a large section of its sequence.
Ribosomes read mRNA in triplets. Adding or removing a number of bases that is not a multiple of three regroups every downstream codon, often changing many amino acids and creating an early stop codon.
Not a multiple of three → frameshift and changed downstream codons. Multiple of three → no frameshift, but amino acids are added or removed. A major insertion or deletion can still disrupt structure and function even without a frameshift.
Deleting one base near the start of a coding sequence shifts the triplet grouping for most of the remaining mRNA and is therefore likely to produce a non-functional polypeptide.
A three-base insertion or deletion avoids a frameshift, but it is not automatically harmless because the added or missing amino acid may be important.
Mutations Arise from Replication Errors and Mutagens
Gene mutations can result from errors in DNA replication or repair and from DNA damage caused by mutagens.
| Cause | Example or route to mutation |
|---|---|
| Replication error | An incorrect nucleotide escapes proofreading |
| Repair error | Damaged DNA is repaired with an altered base sequence |
| Chemical mutagen | NNK in tobacco smoke can increase DNA base-sequence changes |
| Ultraviolet radiation | UV can create abnormal links between adjacent bases |
| Ionizing radiation | X-rays or gamma rays can damage DNA, including strand breaks |
Damage is not yet a permanent mutation if accurate repair restores the original sequence. It becomes a mutation when the altered sequence remains and is copied.
A mutagen increases mutation probability; it does not produce the same mutation in every exposed cell.
Causes of mutation
Assessment in practice
1–2 marksHow it is assessed
This objective is assessed through structured response, commonly using State / Explain / Evaluate.
Command terms
State / Explain / Evaluate / Identify
What earns marks
Build the answer around this relationship: Mutagens increase the frequency of DNA sequence changes.
Watch for
Giving vague environmental factors without identifying radiation, chemicals or carcinogens.
Representative question
Question 1
[Maximum number: 2]
Explain how chemical substances can cause cancer.
a. cause mutations/act as mutagens;
b. in genes that control the cell cycle/cell division;
c. convert proto-oncogenes to oncogenes;
e. mutations in tumour suppressor genes;
2
Marking guidance:
max
Mutation Occurs Randomly Relative to Need
Mutations occur randomly with respect to an organism's need: no known natural mechanism deliberately changes a particular base in order to create a useful trait.
A mutation can occur anywhere in the genome before its consequence is tested by the environment. Natural selection later changes variant frequencies because some carriers reproduce more successfully.
Random relative to need does not mean uniform probability. Base identity and sequence context, DNA repair, gene activity and mutagen exposure can make some sites or cells more likely to mutate than others.
Antibiotic exposure does not instruct bacteria to make a resistance mutation. A resistant variant may already exist, then increase in frequency when susceptible cells die.
Mutation bias can make some changes more frequent without making them purposeful or directed toward advantage.
Randomness in mutation
Assessment in practice
1 marksHow it is assessed
This objective is assessed through multiple choice.
What earns marks
Build the answer around this relationship: Mutations are not directed by an organism’s needs.
Representative question
Question 1
[Maximum number: 1]
What is a feature of mutations?
A
They occur randomly.
B
They only occur in germ cells.
C
The frequency cannot be increased by external factors.
D
They only occur in certain base sequences of the genome.
A
Germline and Somatic Mutations Have Different Reach
The consequence of a mutation depends on whether it occurs in the germ line or in a somatic cell lineage.
| Location | Who can receive the mutation? | Important consequence |
|---|---|---|
| Germ-line cell or gamete | Offspring, if the mutated gene is transmitted at fertilization | The mutation can be inherited and enter the descendant's cell lineages |
| Somatic cell | Descendant body cells produced by mitosis | A clone of altered cells can form; mutations affecting growth control can contribute to cancer |
A mutation in a sperm cell may be inherited by a child, whereas a mutation acquired in one skin cell can spread through a local clone but is not normally passed to offspring.
Somatic does not mean harmless: a non-inherited mutation can still cause cancer or other serious effects in the individual.
Consequences in germ vs. somatic cells
Assessment in practice
1–3 marksHow it is assessed
This objective is assessed through multiple choice, commonly using Distinguish.
Command terms
Distinguish
What earns marks
Build the answer around this relationship: Only germ-line mutations can normally be passed to offspring.
Watch for
Saying any mutation can automatically be inherited regardless of cell type.
Representative question
Question 1
[Maximum number: 1]
A mutation in which type of cell could be inherited?
A
Beta cell in the pancreas
B
T-cell in the lymph
C
Sperm cell in the testis
D
Skeletal muscle cell in the diaphragm
C
Mutation Supplies Variation for Natural Selection
Gene mutation is the original source of new alleles and therefore of all genetic variation.
Most mutations are neutral or harmful to an individual, but a population needs heritable variants for natural selection to act on. Selection changes allele frequencies; it does not create the initial DNA differences.
Mutation creates a new allele → inheritance can place it in a population → environmental conditions affect reproductive success → natural selection can change its frequency over generations.
A new allele that improves drought survival may spread when carriers leave more offspring in dry conditions, while the same allele may provide no advantage in another environment.
Mutation alone is not adaptation. The variant must be heritable and influence reproductive success in the relevant environment.
Mutation as source of variation
Assessment in practice
1 marksHow it is assessed
This objective is assessed through multiple choice.
What earns marks
Build the answer around this relationship: Mutation produces new alleles.
Representative question
Question 1
[Maximum number: 1]
What causes variation in both sexually and asexually reproducing organisms?
A
Mutations
B
Polygenic inheritance
C
Crossing over
D
Independent assortment
A
Core Mutation Effects
Gene mutations are changes in the base sequence of DNA; main types are substitution, insertion, deletion, and duplication. Base substitutions can create SNPs and change codons; degeneracy can make substitutions silent, missense, or nonsense. Insertions or deletions not in multiples of three cause frameshifts that alter downstream codons and often disrupt protein function. Mutations can arise from replication errors, repair errors, or chromosome damage; mutagens include chemicals, ionizing radiation, and ultraviolet radiation. Mutations occur randomly with respect to organism need or advantage; mutation rate varies with DNA sequence, gene expression, repair, and mutagen exposure. Germ-line mutations can be inherited by offspring; somatic mutations affect only descendant body cells and can contribute to cancer. Mutation is the original source of new alleles and genetic variation; many are neutral or harmful, but variation supplies material for natural selection.
Objective notes
7 learning objectivesD1.3.1Gene mutations• Gene mutations are changes in the base sequence of DNA• Main types are substitution, insertion, deletion, and duplication4% of analysed papers 6 papers · 6 questionsViewD1.3.2Base substitution consequences• Base substitutions can create SNPs and change codons• Degeneracy can make substitutions silent, missense, or nonsense4% of analysed papers 6 papers · 6 questionsViewD1.3.3Insertion and deletion consequences• Insertions or deletions not in multiples of three cause frameshifts• Frameshifts alter downstream codons and often disrupt protein function0% of analysed papers ViewD1.3.4Causes of mutation• Mutations can arise from replication errors, repair errors, or chromosome damage• Mutagens include chemicals, ionizing radiation, and ultraviolet radiation3% of analysed papers 4 papers · 6 questionsViewD1.3.5Randomness in mutation• Mutations occur randomly with respect to organism need or advantage• Mutation rate varies with DNA sequence, gene expression, repair, and mutagen exposure1% of analysed papers 1 paper · 1 questionViewD1.3.6Consequences in germ vs. somatic cells• Germ-line mutations can be inherited by offspring• Somatic mutations affect only descendant body cells and can contribute to cancer2% of analysed papers 3 papers · 3 questionsViewD1.3.7Mutation as source of variation• Mutation is the original source of new alleles and genetic variation• Many mutations are neutral or harmful, but variation supplies material for natural selection1% of analysed papers 2 papers · 2 questionsView