Random components in mutagenesis

The mutability of DNA varies enormously from one base pair to another. Part of this variation is due to the specificity of the reaction between mutagen and base, but much of the variation is due to unknown causes. A genetic system developed by Miller and colleagues1 allows the mutation frequencies of a large number of different base pairs in the lacI gene of Escherichia coli to be compared. For example, Coulondre and Miller2 found that the sites most readily mutated by UV light are almost 100 times more often mutated than the least susceptible sites. A recently completed study3 of mutagenesis with neocarzinostatin (NCS) in the lacI gene has prompted us to re-examine some previous studies2,4,5 of mutagenesis in this gene. Our analysis, reported here, suggests that the mutations induced by certain mutagens fall into two classes: mutations in one class are clearly distributed non-randomly, that is, they are very common at some sites and significantly less common at others; mutations in the second class, however, occur at low frequency and appear to be randomly distributed. Both classes of mutations seem to occur only at damaged bases.