Idiosyncratic epistasis creates universals in mutational effects and evolutionary trajectories

Patterns of epistasis and shapes of fitness landscapes are of wide interest because of their bearings on a number of evolutionary theories. The common phenomena of slowing fitness increases during adaptations and diminishing returns from beneficial mutations are believed to reflect a concave fitness landscape and a preponderance of negative epistasis. Paradoxically, fitness decreases tend to decelerate and harm from deleterious mutations shrinks during the accumulation of random mutations-patterns thought to indicate a convex fitness landscape and a predominance of positive epistasis. Current theories cannot resolve this apparent contradiction. Here, we show that the phenotypic effect of a mutation varies substantially depending on the specific genetic background and that this idiosyncrasy in epistasis creates all of the above trends without requiring a biased distribution of epistasis. The idiosyncratic epistasis theory explains the universalities in mutational effects and evolutionary trajectories as emerging from randomness due to biological complexity.