Sign epistasis is less likely to occur between mutations with large effects. (a) Examples of a smooth landscape with paths of monotonically increasing fitness (left) and a rugged landscape characterized by reciprocal sign epistasis (right). (b) Experimentally measured probability of observing sign epistasis as a function of the log growth of two single knockouts with similar effects (G01 = G10 within 20%, G = mean(G01, G10)). The blue shaded area is the standard error of the mean computed by bootstrap.
Velenich and Gore Genome Biology 2013 14:R76 doi:10.1186/gb-2013-14-7-r76