A new direction for directed mutation?

Directed mutation is a controversial process that allows mutations to occur at higher frequencies when they are beneficial. Here we review evidence for transposon-mediated directed mutation. crp deletion mutants (Glp–) of Escherichia coli (E. coli) mutate specifically to glycerol utilization (Glp+) at rates that are enhanced by glycerol or the loss of the glycerol repressor (GlpR), and depressed by glucose or glpR overexpression. Of the four tandem GlpRbinding sites (O1-O4), O4 specifically controls glpFK expression while O1 controls mutation rate. Mutation is due to insertion of the IS5 transposon into a specific site upstream of the glpFK promoter. Mutational control by GlpR is independent of the selection and assay procedures, and IS5 insertion into other gene activation sites is unaffected by the presence of glycerol or the loss of GlpR. The results establish an example of transposon-mediated directed mutation, identify the protein responsible for its regulation, and define essential features of the mechanism involved. We discuss this phenomenon from an evolutionary standpoint and provide examples of analogous switch mechanisms that may or may not be directed.