Summary of compensatory mutations.

a<p>Type refers to the two types of first mutations. I indicates the first mutations, which increase the MFE of ancestral HSR; II indicates the first mutations, which decrease the MFE of ancestral HSR (see text for details).</p>b<p>ECO (EFE) refers to the pair of ancestral-extant HSRs in <i>Escherichia coli</i> (<i>Escherichia fergusonii</i>); Random refers to the pair of ancestral-random HSRs, which were obtained by randomly generating the synonymous mutations based on the number of synonymous substitutions in corresponding ancestral-extant HSRs and the genomic frequency of codons.</p>c<p>Percentage refers to the percentage of the first mutations, which decrease the MFE of ancestral HSR while compensatory mutations exist to partly restore this disruption. Two or more compensatory mutations were observed in a few first mutations. Thus, the percentage is lower than the ratio: Number of compensatory mutations/Number of first mutations.</p>d<p>Paired means that the first mutated base is paired with the second mutated base, while unpaired means that the two mutated bases are unpaired.