Nonsense Mutations

Of the 64 codons 61 code for amino acids, while three are terminations codons which do not specify any amino acid. The three terminations are UAA, UAG and UGA. Any mutations resulting in the alteration of a codon specifying an amino acid to a termination codon is called a nonsense mutation. Thus if the codon UAC (for tyrosine) undergoes a one-base substitutions (C→G) it becomes UAG, a termination Condon.

A nonsense mutation brings about termination of polypeptide synthesis at that point (unless there is genetic suppression: see later part of this chapter). As a result the polypeptide chain synthesized is incomplete. Such chains are likely to be biologically inactive. Since a nonsense mutation brings about a relatively drastic change in the enzyme synthesized it is more likely to have a deleterious effect on the phenotype than missense mutations.

Polypeptide chain synthesis takes place in the 5’→3’ direction. Therefore a nonsense mutation near the 5’ end results in a very short chain with probably very little or no biological activity. Conversely, a nonsense mutations near the 3’ end results in a chain which is nearly complete, and which may have some or normal biological activity.