Evolutionary coupling range varies widely among enzymes depending on selection pressure.

Recent studies proposed that enzyme-active sites induce evolutionary constraints at long distances. The physical origin of such long-range evolutionary coupling is unknown. Here, I use a recent biophysical model of evolution to study the relationship between physical and evolutionary couplings on a diverse data set of monomeric enzymes. I show that evolutionary coupling is not universally long-range. Rather, range varies widely among enzymes, from 2 to 20 Å. Furthermore, the evolutionary coupling range of an enzyme does not inform on the underlying physical coupling, which is short range for all enzymes. Rather, evolutionary coupling range is determined by functional selection pressure.