Fig. 2.

The distribution of epistasis as the selection coefficient $\eta$ increases. (A and B) The normalized distribution of the epistasis in protein stability between (A) native contacts and (B) nonnative contacts when evolving proteins under varying degrees of selection for cooperativity. As selection for cooperativity increases, more native contacts experience higher-magnitude (more negative) epistasis, while more nonnative contacts experience very low levels of epistasis. The area under each curve 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 50,000 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 $\eta$ increases and the variance in the distribution increases. The average of the epistasis distribution at the nonnative contacts goes to zero as the selection coefficient $\eta$ increases, and the variance decreases.