MutationsEdexcel A-Level Biology A: Revision notes
Section 1
What is a mutation?
A mutation is a change in the base sequence of DNA. Mutations can arise spontaneously, for example from errors in DNA replication, and the rate is increased by mutagens such as ionising radiation and some chemicals.
A mutation in a gene can change the sequence of codons in the mRNA, which can change the amino acid sequence (primary structure) of the protein. If the protein's shape and function change, this can lead to disease.
Section 2
Errors in DNA replication
During replication DNA polymerase matches free nucleotides to the template strand by complementary base pairing. Occasionally it makes an error, for example:
- inserting an incorrect nucleotide (a non-complementary base)
- adding an extra nucleotide
- missing out a nucleotide
Most errors are corrected by proofreading. An error that is not corrected is copied every time the DNA replicates, so it becomes a permanent mutation in the new DNA molecules and, if it is in a gamete or an early embryo, may be inherited.
Section 3
Types of gene mutation
Substitution: one base replaced by another. The effect depends on the new codon:
- Silent: the new codon codes for the same amino acid (degenerate code), so no change.
- Missense: a different amino acid is coded for, which may or may not change the protein's function.
- Nonsense: a stop codon is created, so the polypeptide is shorter.
Insertion or deletion of bases: if the number of bases is not a multiple of three, a frameshift occurs and every codon after the change is altered. If three bases are deleted, one amino acid is lost but the rest of the sequence is unchanged.
A single base change does not always change the protein. A single base deletion nearly always does.
Section 4
From mutation to protein
The route from a mutation to a changed protein is:
base sequence → codons → amino acid sequence (primary structure) → bonds between R groups → tertiary structure → function.
A change in primary structure can alter where hydrogen bonds, ionic bonds and disulfide bridges form, so the shape of the protein, including an active site or a channel, may change and the protein may not work. A stop codon gives a shortened polypeptide, which is usually non-functional.
Section 5
Cystic fibrosis and the CFTR gene
Cystic fibrosis is a genetic disease caused by mutations in the CFTR gene. This gene codes for a channel protein in the cell-surface membranes of epithelial cells, which lets chloride ions leave the cell.
Many different mutations of the CFTR gene cause cystic fibrosis. The most common is a deletion of three bases that removes one amino acid, phenylalanine. This changes the primary structure, so the protein folds incorrectly and does not reach the membrane. Other mutations include substitutions and deletions or insertions that cause frameshifts or stop codons.
Section 6
How cystic fibrosis causes symptoms
If the CFTR channel does not work:
- chloride ions cannot leave the epithelial cells
- less water leaves the cells by osmosis
- the mucus becomes thick, sticky and dehydrated
- the mucus is hard to move, so bacteria are trapped and cause lung infections; mucus can also block the pancreatic ducts
The chain of events is: gene mutation → altered CFTR protein → no chloride transport → less water movement → thick mucus.
The CFTR protein transports chloride ions, not water. Water follows by osmosis.
That's the notes covered.
Carry on to the next subtopic.
Exam questions on Mutations
- The coding strand of part of a gene has the base sequence CAG TTA GGC. After an error during DNA replication, the same part of the gene in one daughter cell has the base sequence CAG TAA GGC. The mRNA has the same sequence as the coding strand, with uracil in place of thymine, and UAA is a stop codon.Explain how an error in DNA replication could produce this change in the base sequence.2 marks
- The coding strand of the start of a gene has the base sequence ATG GAA CTT AGC. In one person a mutation deletes a single base, the G at the start of the second triplet, so the sequence reads ATG AAC TTA GC.Explain how this mutation could change the structure of the protein made from this gene.2 marks
- Cystic fibrosis is caused by mutations in the CFTR gene, which codes for a protein that forms a channel for chloride ions in the cell-surface membranes of epithelial cells. The most common mutation is a deletion of three bases, which removes one amino acid, phenylalanine, from the CFTR protein. The altered protein is folded incorrectly and does not reach the cell-surface membrane.Explain how the deletion of three bases in the CFTR gene leads to a protein that cannot function as a chloride ion channel.3 marks
Written by the Exaim team, led by Shaun Daswani (Head of Upper Secondary, Improve ME Institute; MSc Financial Mathematics, Imperial College London; BSc, UCL) and Jason Daswani (operational lead, Improve ME Institute; LSE).