Biophysics-based fitness landscape (FL).
A: A two dimensional slice of the Γ dimensional FL. Fitness values are shown in grayscale and pairs of mutations are represented by colored arrows. Deleterious mutations interact synergistically (yellow/red pair). Compensatory and non-epistatic mutations are also possible (yellow/green and yellow/yellow pairs, respectively). Mutations that push ΔG>0 cause lethality. B: Distribution of mutational thermodynamic effects p(ΔΔG). Our approximation for p(ΔΔG) agrees with experimental values obtained via thermal (black bars) and/or solute (red bars) denaturation. The ∼4,000 experimental values were taken from the ProTherm database . C: The distribution of fitness effects (DFE) among new random mutations from our model (black curve) and several viral species (colored bars). The horizontal axis is the selection coefficient, which depends on fitness before and after the mutation: s≡Wafter/Wbefore−1. The DFE from this model depends on N and U ; here N = 10240, U = 2 (chosen so that the population was near the extinction threshold). See Methods and ref.  for procedures used to obtain the DFE.