The possible involvement of CHI sequences in adaptive mutagenesis: evidence from sequence analysis

Recently we proposed that sequences in the immediate neighbourhood of cytos ine residues whose sequence context permits their methylation by DNA cytosi ne methyltransferase (Dcm) experience hypermutagenesis in cells exposed to nonlethal stresses. This hypothesis could explain the peculiar spectrum of the late-arising Lac(+) mutants seen in the E. coli strain FC40. Here we pr esent results of computer analysis which show that Dcm substrate sequences are overrepresented in the E. coli genome. Interestingly certain noncanonic al Dcm sequences are more overrepresented than the canonical one. The most overabundant of these, DCM-III (5'GCTGG3'), forms the 5' end of the recombi nogenic octamer CHI (5' GCTGGTGG3'). CHI is even more overrepresented than DCM-m. We propose that the overabundance of the DCM and CHI sequences is du e to their ability to enhance adaptive fitness of the host by inducing hype rmutagenesis in cells exposed to nonlethal, growth-blocking stresses. The C HI context seems to stimulate the adaptive activity of DCM-III by a mechani sm which may not directly involve its recombinogenic activity.