The changes seen in DNA sequences at the molecular level suggest that a continuum of mutational effects exists, such that newly arising mutations may be strongly deleterious, weak or neutral in effect or strongly advantageous. The recent crop of fully sequenced microbial genomes provide a rich resource for evolutionary analyses and here we use genome sequences of the enteric bacteria, Escherichia coli and Salmonella enterica to examine molecular evolution in the prokaryotes, finding high levels of adaptive evolution in both species. As there is evidence that slightly deleterious mutations are segregating in both of these species, we tested the assumption that slightly deleterious mutations downwardly bias estimates of adaptive amino acid substitution and look at ways to remove such a bias. We then examined theoretically a model of molecular sequence evolution which allowed some proportion of new mutations to be slightly advantageous and looked for evidence of this using a comparative method. We show that there is some support for a model of molecular evolution that allows slightly advantageous compensatory evolution and that such compensatory evolution may follow an expansion in population size. Finally, we compared intergenic regions from E. coli and Salmonella to look at the patterns of molecular evolution in non-coding DNA from these species.