Fig. 4.

The distribution of epistasis as the selection coefficient ${\eta }_E$ increases. (A and B) The normalized distributions of epistasis between (A) native and (B) nonnative contacts when evolving sequences under different magnitudes of selection for the average magnitude of epistasis between the native contacts. As the value of the selection coefficient ${\eta }_E$ increases, a higher number of native contacts experience greater magnitude negative epistasis, while a higher number of nonnative contact pairs experience nonzero epistasis. The area under the curves sums to 1. (C and D) The mean of the epistasis distributions (C) and the variance of the epistasis distribution (D), of the final 2,000 generations of the 5,000 generations simulated, averaged over all 10 simulations for native contacts (blue) and nonnative contacts (red). The error bars represent the variance of these values across the 10 simulations. The average of the epistasis distribution at the native contacts becomes more negative as the value of the selection coefficient ${\eta }_E$ increases and the variance in the distribution increases. The average of the epistasis distribution at the nonnative contacts remains roughly constant as the selection coefficient ${\eta }_E$ increases, but the variance in the distribution increases.