Fig. 4: Changes in ligand concentration switch between-allele interactions.

a, b, c The relationships between the observed and expected phenotypes with additive expectation when combining two detrimental mutants within- (a), between (b) heterozygous alleles or homozygous alleles (c) at different ligand-protein ratios. d–g Heatmaps show how two mutations combine within - (d, e) between heterozygous alleles (f), or homozygous alleles (g) when they both affect the same biophysical parameters: protein-folding (d, f, g) or ligand-binding (e, f, g). For both between-allele mutant combinations, folding or binding double mutants are shown together since they are not distinguishable (f, g). Black lines indicate phenotypic iso-chores.