Figure 4.

Model for the buffering of expression variations by large-scale regulators. Squares represent the space of possible mutations and circles represent the fraction of mutations that are (slightly) deleterious for the wild type (WT, blue), mutant (red) or both (purple). A genetic capacitor modulates the effects of mutations in both ways because of epistatic interactions: it buffers the deleterious effects of some mutations while aggravating the effects of other mutations (that is, these mutations are deleterious for the wild type but not for the mutant). As the wild type (and not the deletion mutant) is the product of evolution, natural selection has rejected mutations that are deleterious for the wild type, but accumulated many mutations that are slightly deleterious for the deletion mutant. As a result, deletion of large-scale regulators unleashes the slightly deleterious effects of various mutations and, thus, increases the variability between different strains or species (which accumulated different sets of buffered mutations).