Cumulative numbers of synonymous and nonsynonymous substitutions along the domains; numbers were counted with the snap program. For intramolecular comparisons, only D1 and D2 are shown; similar results were obtained for D1/D3 and D2/D3. For intermolecular comparisons, only the first domain pairs are shown; the other two gave the same result. (A) The changes in the cumulative numbers of the nonsynonymous substitution rates between the domains are similar along the domains for all LCFs, with pronounced reductions in the central regions. (B) The cumulative numbers of synonymous substitutions for intramolecular domains, especially for the first domain as compared with one of the other two, are lower in the central region for Lp and Pr LCFs but not for others. (C and D) Similar comparisons also were carried out pairwise for corresponding domains of different LCFs. Both the cumulative numbers of nonsynonymous substitutions and those of synonymous substitutions increase at about the same rate along the entire domain; the absolute numbers are smaller for the more closely related LCFs, such as At vs. Pr.