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

Adaptation dynamics on fitness landscapes is often studied theoretically in the strong-selection, weak-mutation 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 while it is known to slow down the rate of adaptation (when compared to the strong-selection, weak-mutation model with the same parameters), how it affects the shape 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 shape 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 rescaled fitness trajectory (where adaptation speed is measured relative to its value at the start of the experiment), while an enhancement of the beneficial mutation rate does the opposite of slowing it down. 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).