Consequences of Base Substitutions
- Base substitutions are a mutation that occurs when a base in the DNA sequence is randomly swapped for a different base
- A substitution mutation can only change the amino acid for the triplet in which the mutation occurs; it will not have a knock-on effect on the rest of the sequence
- A base substitution can result in single nucleotide polymorphisms, frequently called SNPs (pronounced “snips”)
- These represent a difference in a single DNA nucleotide. E.g. a SNP may replace the nucleotide cytosine (C) with the nucleotide thymine (T) in a certain stretch of DNA
- SNPs occur normally throughout a person’s DNA
- They occur once in every 300 nucleotides on average, which means there are roughly 10 million SNPs in the human genome
- SNPs are commonly found in the non-coding regions of DNA between genes
- They can act as biological markers, helping to locate genes that are associated with disease
The effect of SNPs
- Substitution mutations can take three forms which may or may not change the amino acid of a polypeptide chain:
- Silent mutations – the mutation does not alter the amino acid sequence of the polypeptide (this is because certain codons may code for the same amino acid as the genetic code is degenerate)
- Missense mutations – the mutation alters a single amino acid in the polypeptide chain (sickle cell anaemia is an example of a disease caused by a single substitution mutation changing a single amino acid in the sequence)
- Nonsense mutations – the mutation creates a premature stop codon (signal for the cell to stop translation of the mRNA molecule into an amino acid sequence), causing the polypeptide chain produced to be incomplete and therefore affecting the final protein structure and function (cystic fibrosis is an example of a disease caused by a nonsense mutation, although this is not always the only cause)