The selection of a strain with the desired properties appears to have occurred in at least two discrete steps, as shown by the genome sequences and metabolic profiles. The initial step appears to have been the adaptation of a strain to growth in corn steep liquor, an acidic medium rich in protein and lactate [44] . The robust growth of the Detrick strains relative to 1942 in low-pH medium containing high lactate levels is likely due to mutations in mmgD (2-methylcitrate synthase, position 2029530), or a short-chain 3-oxoacyl-[acyl-carrierprotein] reductase (position 3437350), or both. The most likely candidate for a mutation in the Detrick isolates that increases growth is the frameshift in mmgDthat occurred following the divergence from the 49822 lineage and results in an altered C-terminus ( Figure S1 ). The mmgD geneencodes a 2-methylcitrate synthase that is expressed in the mother cell at the intermediate stages of sporulation [45] . A null mutation in mmgD had no perceptible effect on sporulation, although other TCA-cycle enzymes when mutated led to a loss of sporulation [45] . The effects of the frameshift mutation on sporulation and cellular physiology on the function of the enzyme are not clear at this time. We speculate that the frameshift mutation alters the substrate specificity of MmgD in favor of citrate, thus increasing the flux of lactate-derived intermediates through the tricarboxylic acid cycle. Evidence for this possibility includes the observations that 2-methylcitrate synthases can have partial citrate synthase activity [45] and that the B. subtilis mmgD gene can complement a gltA (citrate synthase) mutant of E. coli [46] . Alternatively, alteration of function of mmgD may have predisposed the lactate-adapted strain to acquisition of a hypersporulating phenotype, which is not readily isolated or stable in B. subtilis (see below); however the presence of a hypersporulating phenotype in an independently evolved lineage (1013) of BG indicates that the species may have an intrinsic predisposition to evolving such a phenotype in vitro.