What is a Point Mutation?

A genetic mutation is any change in the DNA code (genome) of a cell. Of all the ways the genome can be changed, the simplest type of mutation is the point mutation. In a point mutation, a single base is substituted for another, changing the meaning of a single codon, leaving the rest of the gene unchanged. Geneticists recognize four types of point mutations, based on the effect on the genome.

With 61 codons for 20 amino acids, many of the codons are "synonyms," coding for the same amino acid. Each amino acid can be indicated by up to six different codons (in the case of leucine); only two (methionine and tryptophan) have only one codon. In most cases, the synonyms differ by only one base, so it is possible for a point mutation to result in a codon for the same amino acid.

For example, the DNA codons CAA, CAG, CAT, and CAC all code for the amino acid valine. If a strand of DNA undergoes a point mutation in the codon CAA that changes it to CAG, it would still code for valine. This type of substitution is called a synonymous or sense mutation; it is also known as a silent mutation because there is no change in the amino acid sequence. (Find out how "silent" mutations can still have an effect on the gene and its resulting protein.)

A missense mutation is a point mutation that causes a codon to code for a different amino acid. The most notorious missense mutation is the one that causes sickle cell anemia. In this disease, one of the codons in an important hemoglobin gene has changed from CTC to CAC, resulting in the amino acid valine instead of glutamic acid. Chemically, these two amino acids are very dissimilar, so this simple change has a significant effect on the structure of hemoglobin protein, causing the disease symptoms.

A missense mutation might be less significant if the change is between two similar amino acids. For example, a change from CTC (glutamic acid) to CTG (aspartic acid) may not have a dramatic effect on the resulting protein because these two amino acids are similar (both are acidic).

Three codons in the genetic code tell the cell to stop adding amino acids to a protein because the end of the gene has been reached. In a nonsense mutation, a codon that stands for an amino acid mutates to one of these three stop codons. (The term "nonsense mutation" is used because the stop codon has "no sense" for an amino acid—as opposed to a "missense mutation," in which the resulting codon has the "wrong sense" for an amino acid.) Nonsense mutations cause the protein to be cut off early and therefore incomplete, which usually renders it non-functional. Cystic fibrosis is a disease caused by a nonsense mutation.

A stop-codon mutation is the opposite of a nonsense mutation: it changes a stop codon into a codon for an amino acid, causing the protein to become too large. The added section may consist of part of another protein from the genome—or it may be complete "gibberish," if the addition comes from a non-coding region of DNA. This lesser-known type of mutation, like a nonsense mutation, generally renders its protein non-functional, and may even result in a harmful protein. A rare disease called familial British dementia is caused by a stop-codon mutation that causes mutated amyloid protein to "clog" the brain (see Nature vol. 399 (1999), pp. 776-781).

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