Evolution of binding sites. (a) Binding energy pairs (E1, E2) for 32 experimentally verified CRP binding sites in E. coli from the DPInteract database  and their aligned orthologs in S. typhimurium (dots). Conditional expectation value for the binding energy in S. typhimurium under neutral evolution, ⟨G0(E2|E1)⟩ (dashed line), and under selection, ⟨G
(E2|E1)⟩ (solid line). (b) Distribution of energy pair counts Wdat(E1, E2) (filled contours), compared to the distribution W(E1, E2) given by the Bayesian model (62). The symmetry of these distributions under exchange of E1 and E2 reflects detailed balance of the substitution dynamics. From [16,39].