A point mutation, or substitution, is a type of mutation that causes the replacement of a single base nucleotide with another nucleotide. Often the term point mutation also includes insertions or deletions of a single base pair (which have more of an adverse effect on the synthesized protein due to nucleotides still being read in triplets, but in different frames- a mutation called a frameshift mutation). For coding sequences one can categorize such point mutations as follows:
- nonsense mutations: code for a stop, which can truncate the protein.
- missense mutations: code for a different amino acid.
- silent mutations: code for the same amino acid.
For example , sickle-cell disease is caused by a single point mutation (a missense mutation) in the beta hemoglobin gene that converts a GAG codon into GTG, which encodes the amino acid valine rather than glutamic acid.
Point mutations that occur in non-coding sequences are most often without consequences, although there are exceptions. If the mutated base pair is in the promoter sequence of a gene, then the expression of the gene may change. Also, if the mutation occurs in the splicing seat of an intron, then this may interfere with correct splicing of the transcribed pre-mRNA.
Point mutations may arise from spontaneous mutations that occur during DNA replication. The rate of mutation may be increased by mutagens. Mutagens can be physical, such as radiation from UV rays, X rays or extreme heat, or chemical (molecules that misplace base pairs or disrupt the helical shape of DNA). Mutagens associated with cancers are often studied to learn about cancer and its prevention.