Molecular handles on adaptive mutation

In one experimental system, several handles on the molecular mechanism of apparent adaptive mutation have emerged. The system is reversion of a lac frame‐shift mutation in Escherichia coli. The molecular handles include a requirement for homologous recombination; the implication of DNA double‐strand breaks as a molecular intermediate; a unique sequence spectrum of −1 deletions in mononucleotide repeats which implies polymerase errors, and also implies a failure of post‐synthesis mismatch repair on those errors; and the involvement of sexual functions at some stage of the process. These molecular handles are revealing an unexpected new mechanism of mutagenesis.