||E. coli and S. enterica diverge at a synonymous substitution rate of 0.90% per million years (25, 26), which corresponds to a within lineage rate of 0.0045 mutations per site per million years. Natural populations of E. coli have an estimated 100– 300 generations per year (37–39), implying a rate of about 0.0001 to 0.0002 mutations per genome per generation (Table 1). Drake et al.’s estimate (20–22), based on laboratory derived mutation rates, was 0.003 mutations per genome BNID 102008,103918, more than an order of magnitude higher. Similar calculations for Buchnera, whose generation times can be estimated from the number of replications within the host insect and the number of host generations per year (19, 40–42), result in 0.0001 to 0.0002 mutations per genome per generation, a rate identical to that estimated for E. coli. Hence, the genomic mutation rate may well be constant across bacterial species on an evolutionary time scale, but it is not compatible with the rate based on laboratory studies.