T Residues Preceded by Runs of G are Hotspots of T to G Mutation in Bacteria

Abstract

The rate of mutation varies among positions in a genome. Local sequence context can affect the rate, and has different effects on different types of mutation. Here I report an effect of local context that operates to some extent in all bacteria examined: the rate of T[->]G mutation is greatly increased by preceding runs of three or more G residues. The strength of the effect increases with the length of the run. In Salmonella, in which the effect is strongest, a G run of length three increases the rate by a factor of ~26, a run of length four increases it by almost a factor of 100, and runs of length five or more increase it by a factor of more than 400 on average. The effect is much stronger when the T is on the leading rather than the lagging strand of DNA replication. Several observations eliminate the possibility that this effect is an artifact of sequencing error.