Inigo Martincorena, Nicholas M. Luscombe
(Submitted on 5 Nov 2012)
In a short article submitted to ArXiv , Maddamsetti et al. argue that the variation in the neutral mutation rate among genes in Escherichia coli that we recently reported  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.