The effect of weak clonal interference on average fitness trajectories in the presence of macroscopic epistasis

Abstract

Adaptation dynamics on fitness landscapes is often studied theoretically in the strong-selection, weak-mutation (SSWM) regime. However, in a large population, multiple beneficial mutants can emerge before any of them fixes in the population. Competition between mutants is known as clonal interference, and how it affects the form of long-term fitness trajectories in the presence of epistasis is an open question. Here, by considering how changes in fixation probabilities arising from weak clonal interference affect the dynamics of adaptation on fitness-parameterized landscapes, we find that the change in the form of fitness trajectory arises only through changes in the supply of beneficial mutations (or equivalently, the beneficial mutation rate). Furthermore, a depletion of beneficial mutations as a population climbs up the fitness landscape can speed up the functional form of the fitness trajectory, while an enhancement of the beneficial mutation rate does the opposite of slowing down the form of the dynamics. Our findings suggest that by carrying out evolution experiments in both regimes (with and without clonal interference), one could potentially distinguish the different sources of macroscopic epistasis (fitness effect of mutations vs. change in fraction of beneficial mutations).