What you need to know
- 2.14(i)substitutionA mutation in which one base is replaced by another., insertionA mutation in which one or more extra bases are added to the DNA sequence. and deletionA mutation in which one or more bases are lost from the DNA sequence. mutationA change in the sequence of bases in DNA. arising from replication errors.
- 2.14(ii)Mutations with no observable effect, genetic disorders and cancer.
By the end, you should be able to…
- Distinguish three types of base-sequence change.
- Explain reading-frame effects with explicit assumptions.
- Link molecular change to possible, rather than inevitable, phenotypeThe observable characteristics of an organism, produced by its genotype interacting with the environment. change.
Build your understanding
A change in the DNA sequence
A mutationA change in the sequence of bases in DNA. is a change in genetic material. During DNADeoxyribonucleic acid: a double-stranded polynucleotide that carries the genetic code. replication, a wrong nucleotideThe monomer of nucleic acids: a pentose sugar, a phosphate group and a nitrogenous base. may be incorporated or bases may be added or missed. If an error is not corrected and becomes established in the DNA sequence, it can be passed to descendant cells.
A substitutionA mutation in which one base is replaced by another. replaces one base with another. An insertionA mutation in which one or more extra bases are added to the DNA sequence. adds one or more bases; a deletionA mutation in which one or more bases are lost from the DNA sequence. removes one or more. These descriptions identify the DNA change, not its final effect. Mutations do not arise because an organism needs a particular change.
Substitutions have several possible outcomes
In a protein-coding region, a substitution can alter an messenger RNAA single-stranded RNA copy of a gene that carries the code from the nucleus to a ribosome. codonA sequence of three bases on mRNA that codes for one amino acid or a stop signal.. Because the code is degenerateDescribes the genetic code: most amino acids are coded for by more than one codon., the altered codon may still specify the same amino acidThe monomer of proteins: a central carbon with an amine group, a carboxyl group, a hydrogen and an R group.: for example UUU → UUC still gives phenylalanine.
Other changes specify a different amino acid, or convert an amino-acid codon into a stop codon. A different amino acid may change interactions responsible for folding or an active siteThe region of an enzyme with a specific shape where the substrate binds.. An early stop can produce a shorter polypeptideA chain of many amino acids joined by peptide bonds.. Neither the DNA change alone nor the word “mutation” establishes how severe an effect will be.
Insertions and deletions can shift the reading frame
In a coding sequence read continuously from a fixed start, insertion or deletion of a number of bases not divisible by three shifts the reading frame downstream. Many subsequent codons may change, and a premature stop may appear.
Adding or removing three bases preserves the downstream reading frame, although amino acids can still be added, removed or altered near the site. “No frameshiftA change in the reading frame caused by inserting or deleting bases (not in threes), so every codon after it changes.” does not mean “no effect”. The location and number of bases matter.
From sequence to an observable effect
A mutation may have no observable effect because it is in a region where that change does not affect expression, leaves the amino-acid sequence unchanged, or changes an amino acid without significantly changing function. A recessiveAn allele that is expressed in the phenotype only when no dominant allele is present (when homozygous). effect may also be masked in a heterozygousHaving two different alleles of a gene..
Some mutations impair important proteins and cause genetic disorders. Others affect control of cell division and can contribute to cancer. Cancer commonly involves multiple changes; a mutation is not automatically a cancer diagnosis. A mutation confined to body cells can pass to daughter cells without being inherited by offspring through a gameteA haploid sex cell, such as a sperm or an egg cell..
NOT: every mutation changes the protein, and a frameshift is not a one-amino-acid change.
- Substitution may be silent, missense or nonsense
- Insertion or deletion of a base shifts the reading frame
- A changed protein may cause disease, a new trait, or no clear effect
- Function still depends on where the altered residue sits
Two traps this diagram blocks
- Do not say every substitution changes the amino-acid sequence.
- Do not describe a single-base insertion as changing only the amino acid at that position.
From the diagram alone
Question
Explain how a substitution in a gene could have no effect on the polypeptide. [3]
Show a model answer
The altered DNA base may change one mRNA codon. Because the code is degenerate, the new codon can specify the same amino acid as the original codon. Primary structure is then unchanged, so this mutation need not change folding or function.
Make your reasoning visible
Explain the intermediate steps
Base change → altered codonA sequence of three bases on mRNA that codes for one amino acid or a stop signal., if relevant → possible amino-acid change → possible folding/function change → possible phenotypeThe observable characteristics of an organism, produced by its genotype interacting with the environment.. Do not jump straight from mutationA change in the sequence of bases in DNA. to disease.
State the frameshift condition
Specify an insertionA mutation in which one or more extra bases are added to the DNA sequence. or deletionA mutation in which one or more bases are lost from the DNA sequence. in the coding region with a base count not divisible by three.
Use evidence for “no effect”
A synonymous codon demonstrates unchanged amino-acid sequence in that example. It does not justify claiming every substitutionA mutation in which one base is replaced by another. is harmless.
Key explanations
- If the altered base is in the template used for transcription, the messenger RNAA single-stranded RNA copy of a gene that carries the code from the nucleus to a ribosome. codon can change.
- The effect depends on which residue changes and what that residue does. A similar R group may have little effect.
- A stop codon created early shortens the polypeptideA chain of many amino acids joined by peptide bonds..
- The protein may lose function, gain a harmful property, or show no obvious change. A mutation does not automatically cause disease.
Avoid this misconception
The claim: Every mutation changes an amino acidThe monomer of proteins: a central carbon with an amine group, a carboxyl group, a hydrogen and an R group. and causes disease.
The correction: Some do not change the amino-acid sequence or have no observable effect; others affect function.
What happens to a protein when one base changes?
When DNA is copied, a base can occasionally be swapped, added or missed. If the mistake is not repaired, the gene now carries a mutation, and every copy made from it carries it too.
What the model shows
A short made-up gene (fictional sequences), its mRNA codons and the amino acids they code for. Below it, the same gene after a change you choose, lined up codon by codon so you can compare.
What to look for
How many codons change after a substitution, compared with an insertion or deletion of one base. When a change makes no difference at all. What happens when three bases are deleted.
What it tells us
Substitutions change at most one codon, so they can be silent, change one amino acid, or make an early stop. One base added or removed shifts the reading frame and changes everything after it. Some mutations have no observable effect.
Be careful what you claim
The genes are tiny and fictional. Real cells repair most copying errors, and the model cannot say how a changed amino acid affects the protein’s shape.
Try it in the model: pick base 18 of gene A (an A), substitute it with T and press Apply. Codon GAU becomes GAA: aspartic acid becomes glutamic acid.
Gene mutations and the polypeptide
Substitute, insert or delete bases in a short fictional gene and compare its codons and amino acids with the original, lined up codon by codon.
What you see
- The original gene: its template DNA strand, the mRNA codons read from AUG, and the amino acid each codon codes for.
- Underneath, the same gene after your mutation, lined up codon by codon. Changed codons and amino acids are highlighted; codons after a stop are greyed out.
- A card names the effect and counts the changed codons and amino acids.
How to use it
- Pick a template base, on the picture or in the bar. Choose Substitute, Insert before, Delete one or Delete three, and a new base where needed, then Apply.
- Undo puts the gene back. Gene B has the codon GAA from the lesson.
What it shows
- Substitutions can be silent, missense or nonsense.
- Inserting or deleting one base shifts the reading frame; deleting three keeps it but loses an amino acid.
- The effect on the protein, and so on the organism, depends on the change: many mutations have no observable effect.
Limits of the model
- The genes are made up and very short. Real genes have hundreds or thousands of bases, and many mutations fall outside coding regions.
- In a cell these errors happen during DNA replication, and most are repaired; this model only shows what an unrepaired change does.
- The model cannot tell you how a changed amino acid affects folding or function: that needs evidence from the real protein.
Guided tour · step 1 of 8
- Pick a base on gene A’s template strand: tap it on the picture in the simulator, or in the base bar in Mutate the template strand just below these steps.
- Set Change to Substitute and choose a new base, then press Apply.
- Aim to change one amino acid: try base 18 → T.
One changed base changes one mRNA codon. That can put a different amino acid in the chain: a missense mutation.
Mutate the template strand
Questions
Check your understanding
Try each question before opening the suggested answer.
Practice question
Retrieval and explanation · suggested answer
Distinguish a substitution from an insertion.
Show suggested answer
A substitution replaces a base; an insertion adds bases, changing sequence length.
Practice question
Retrieval and explanation · suggested answer
A codon changes from GAA to GAG; both specify glutamate. Predict the immediate effect on the amino-acid sequence.
Show suggested answer
There is no amino-acid change at this position because the code is degenerate.
Practice question
Retrieval and explanation · suggested answer
Compare deletion of one base with deletion of three consecutive bases within a coding region.
Show suggested answer
One base shifts the downstream reading frame. Three bases preserve that downstream frame but can remove an amino acid and alter sequence near the deletion, with possible effects on function.
Take the idea further
Apply the same specification knowledge to an unfamiliar problem. Any extra assumptions are supplied in the question.
Stretch question
Two proteins differ by one amino acid. One substitution is at the active site; the other is on a distant surface. Can you rank the effects on activity with certainty from location alone?
Show a hint
Location gives a hypothesis, but chemical interactions and folding also matter.
Explore the reasoning
No. An active-site change may disrupt binding or catalysis, but a distant change may affect overall folding or stability. The identities of the amino acids and experimental activity data are needed.
Recall this lesson
Lesson recall questions
Question 1 of 5: Name the type of mutation in which a base is lost from the DNA sequence.
Mutations and their effects
Practice question
Retrieval and explanation · suggested answer
Name the type of mutation in which a base is lost from the DNA sequence.
Try this from memory first.
Put your biology to work
Explore where these ideas appear in the world. Enrichment, not extra required recall.
A tumour’s sequence is evidence
2C · Gene MutationCancer researchers study DNA changes that may affect cell growth. The NCI describes how genetic changes can arise during cell division and how tumour testing can identify changes…Specification 2.14(i) · 2.14(ii)Read & use the scienceClose article
Why this matters
Cancer researchers study DNA changes that may affect cell growth. The NCI describes how genetic changes can arise during cell division and how tumour testing can identify changes relevant to cancer biology. Sequencing a tumour can reveal changes acquired in a lineage of body cells. Comparing that result with suitable non-tumour material helps distinguish acquired changes from variants present more widely in the body. Even then, finding a difference does not automatically prove it caused the cancer: its effect needs interpretation. Cancer genomics therefore combines molecular measurements with evidence about function. This extends mutation biology into research while avoiding the mistaken inference that every cancer-associated variant must have come from a parent.
Back to the specification
Pearson Edexcel IAL Biology · Issue 2, February 2021 · Unit 1, pp. 15–18. The application extends beyond required recall.
- 2.14(i) understand how errors in DNA replication can give rise to mutations (substitution, insertion and deletion of bases)
- 2.14(ii) know that some mutations will give rise to cancer or genetic disorders, but that many mutations will have no observable effect
Use the science
Why does finding a mutation in tumour cells not prove that it was inherited?
Explore a possible response
The mutation could have arisen in a body cell during life. Evidence from appropriate non-tumour cells and inheritance information would be needed.
Explore the source
A mutation is not automatically a tumour
2C · Gene MutationResearchers sequenced small samples of normal sun-exposed skin and found many mutations, including changes associated with cancer. The tissue was not therefore automatically cancerous. The study connects environmental…Specification 2.14(i) · 2.14(ii)Read & use the scienceClose article
Why this matters
Researchers sequenced small samples of normal sun-exposed skin and found many mutations, including changes associated with cancer. The tissue was not therefore automatically cancerous. The study connects environmental exposure, accumulated DNA changes and the difference between a molecular finding and a disease diagnosis. It also challenges a simplistic story in which any mutation produces an immediately visible effect. Cancer development involves additional changes and cellular context. The samples came from a small number of older people having eyelid surgery, so the results should not be treated as a universal measurement for every tissue or age group.
Back to the specification
Pearson Edexcel IAL Biology · Issue 2, February 2021 · Unit 1, pp. 15–18. The application extends beyond required recall.
- 2.14(i) understand how errors in DNA replication can give rise to mutations (substitution, insertion and deletion of bases)
- 2.14(ii) know that some mutations will give rise to cancer or genetic disorders, but that many mutations will have no observable effect
Use the science
Why does finding a cancer-associated mutation in a normal skin sample not prove that the sample is a tumour or that the change will be inherited by a child?
Explore a possible response
Association with cancer does not establish all changes needed for a tumour; tissue behaviour matters. A mutation in somatic skin cells is not automatically present in gametes.
Explore the source
- High burden and pervasive positive selection of somatic mutations in normal human skinMartincorena et al., Science (2015)