Fig 6. A model of how selection transforms the epistatic landscape, enriching for buffering.

This model is schematized similarly to Fig 4A. Pre-selection: inhibiting an epistatic protein has genotype-specific effects on phenotype that result in line crossing. Stabilizing selection will narrow the amount of phenotypic diversity in the natural environment, removing genotypes with extreme phenotypes (light blue circles that fall outside of the grey shaded area). Removing these genotypes from the plot entirely (removing the light blue circles, dotted lines, and connected red circles) results in the post-selection plot. Post-selection: inhibiting an epistatic protein may reveal phenotypes outside of selection’s sieve (grey shaded area).