Fig. 4.

(A) Expected pattern of landscape-wide epistasis measure ${\gamma }_d$ (SI Appendix, Eq. S1_15) with mutational distance for theoretical fitness landscapes with 6 loci from ref. 14. (B) Observed decay of ${\gamma }_d$ with mutational distance under the drop-one approach is quite homogenous, except when hot spot mutation 588P is removed; 95% CIs are contained within the lines for the global landscape. (C) Observed decay of ${\gamma }_d$ for all diallelic six-locus sublandscapes. Depending on the underlying mutations, ${\gamma }_d$ is vastly different, suggesting qualitative differences in the topography of the underlying fitness landscape and in the extent of additivity in the landscape. Three focal landscapes representative of different types and ${\gamma }_d$ for the full landscape have been highlighted. (D) Observed decay of ${\gamma }_d$ for all diallelic four-locus sublandscapes containing the parental type, indicative of locally different landscape topographies. Highlighted are the three focal landscapes. (Insets) Histograms of the roughness-to-slope ratio $r\mathrm{/}s$ for the respective subset, with horizontal lines indicating values for highlighted landscapes [$r\mathrm{/}s$ for global landscape (blue) is significantly different from HoC expectation, $p\mathrm{=}\mathrm{0.01}$]. Similar to ${\gamma }_d$, there is a huge variation in $r\mathrm{/}s$ for subparts of the fitness landscape, especially when considering the four-locus subsets.