[Trends in Evolutionary Biology 2011; 3:e3] [page 13]

Directed mutation is a controversial process that allows mutations to occur at higher fre-quencies 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 GlpR-binding 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 proce-dures, and IS5 insertion into other gene activa-tion sites is unaffected by the presence of glyc-erol 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 phe-nomenon from an evolutionary standpoint and provide examples of analogous switch mecha-nisms that may or may not be directed