  In a short article submitted to ArXiv [1], Maddamsetti et al. argue that the
variation in the neutral mutation rate among genes in Escherichia coli that we
recently reported [2] might be explained by horizontal gene transfer (HGT). To
support their argument they present a reanalysis of synonymous diversity in 10
E.coli strains together with an analysis of a collection of 1,069 synonymous
mutations found in repair-deficient strains in a long-term in vitro evolution
experiment. Here we respond to this communication. Briefly, we explain that HGT
was carefully accounted for in our study by multiple independent phylogenetic
and population genetic approaches, and we show that there is no new evidence of
HGT affecting our results. We also argue that caution must be exercised when
comparing mutations from repair deficient strains to data from wild-type
strains, as these conditions are dominated by different mutational processes.
Finally, we reanalyse Maddamsetti's collection of mutations from a long-term in
vitro experiment and we report preliminary evidence of non-random variation of
the mutation rate in these repair deficient strains.
