Extended Data Fig. 5: Deviation of observed from expected double-mutant growth rates reveals toxin variants with specific or with only non-specific beneficial effects, and fraction of specific vs. non-specific toxin variants.

a, For each beneficial toxin mutation (indicated above each plot) combined with each antitoxin variant indicated on the x axis, the plot shows the growth rate relative to the wild-type toxin–antitoxin pair (mean posterior ∆growth rate(T*/AT* - T/AT)). Grey dots represent T*/AT*, error bars indicate 95% posterior highest density interval. The ∆growth rate for each antitoxin mutant combined with wild-type toxin (T/AT*) is shown (black dots) along with the ∆growth rate for T*/AT* expected under the non-specific, nonlinear model (green dots). b, Deviation of the observed (dots) from the expected double-mutant growth rates (orange line) highlights classification of specific and non-specific toxin variants. Beneficial toxin substitutions (rows, n = 32) ordered by their range of growth rate deviations across deleterious antitoxin variants as in panel b. c-g, Specific vs. non-specific enabling toxin variants under ‘high’ antitoxin expression for all enabling toxin variants grouped by deleterious antitoxin for the more stringent set of 310 ‘most toxic’ toxins (c) and less stringent set of 781 ‘toxic’ toxins (d). Orange and purple indicate mutant pairs involving non-specific and specific, respectively, rescuing mutations in the toxin. Enabling toxin variants under ‘low’ antitoxin expression at different absolute growth rate cutoffs relative to the wild-type toxin/antitoxin growth rate (e), or grouped by ‘most toxic’ (f) or ‘toxic’ (g) toxin variants. h, Inferred non-specific toxin variant effect vs. minimum atom distance to any antitoxin atom for 21 non-specifically rescuing toxin variants (orange). i, j, For specific and non-specific beneficial toxin mutants, the change in growth rate in a deleterious antitoxin mutant background, ∆growth rate (T*/AT* - T/AT*), is plotted vs. minimum atom distance to the deleterious antitoxin mutation it rescues (i) or any antitoxin atom (j) in the ‘low antitoxin’ expression condition.