Figure 3. Genetic interactions between all pairs of mutations switch from positive to negative epistasis in different genetic backgrounds.

a, Proportion of backgrounds (top) and species (middle) in which each pair of mutations interacts positively (orange) negatively (green) at different FDRs (n = 47,649 backgrounds). Bottom shown background-averaged epistasis (n = 87 pairs of mutations). b, Interaction networks for three species (other species in Extended Data Fig. 4b). Edge colours indicate epistasis sign (FDR<0.1) and width strength of interaction. c, Comparison of epistasis scores between these three species (r_s = Spearman correlation coefficient, n = 43, 22 and 6 comparisons from left to right). d, Number of positive (orange) or negative (green) magnitude, sign or reciprocal sign pairwise epistasis (n = 10,330 significant interactions from 47,649 tested) e, Consistency of each interaction quantified as the absolute difference between the % of backgrounds in which the interaction is positive or negative. Colour indicates the predominant sign. The four pairs that restore WC bps are highlighted.