  In a letter published in Molecular Biology Evolution [10], Chen and Zhang
argue that the variation of the mutation rate along the Escherichia coli genome
that we recently reported [3] cannot be evolutionarily optimised. To support
this claim they first attempt to calculate the selective advantage of a local
reduction in the mutation rate and conclude that it is not strong enough to be
favoured by selection. Second, they analyse the distribution of 166 mutations
from a wild-type E. coli K12 MG1655 strain and 1,346 mutations from a
repair-deficient strain, and claim to find a positive association between
transcription and mutation rate rather than the negative association that we
reported. Here we respond to this communication. Briefly, we explain how the
long-standing theory of mutation-modifier alleles supports the evolution of
local mutation rates within a genome by mechanisms acting on sufficiently large
regions of a genome, which is consistent with our original observations [3,4].
We then explain why caution must be exercised when comparing mutations from
repair deficient strains to data from wild-type strains, as different
mutational processes dominate these conditions. Finally, a reanalysis of the
data used by Zhang and Chen with an alternative expression dataset reveals that
their conclussions are unreliable.
