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Interference effects of deleterious and beneficial mutations in large asexual populations

Linked beneficial and deleterious mutations are known to decrease the fixation probability of a favorable mutation in large asexual populations. While the hindering effect of strongly deleterious mutations on adaptive evolution has been well studied, how weak deleterious mutations, either in isolation or with superior beneficial mutations, influence the fixation of a beneficial mutation has not been fully explored. Here, using a multitype branching process, we obtain an accurate analytical expression for the fixation probability when deleterious effects are weak, and exploit this result along with the clonal interference theory to investigate the joint effect of linked beneficial and deleterious mutations on the rate of adaptation. We find that when the mutation rate is increased beyond the beneficial fitness effect, the fixation probability of the beneficial mutant decreases from Haldane's classical result towards zero. This has the consequence that above a critical mutation rate that may depend on the population size, the adaptation rate decreases exponentially with the mutation rate and is independent of the population size. In addition, we find that for a range of mutation rates, both beneficial and deleterious mutations interfere and impede the adaptation process in large populations. We also study the evolution of mutation rates in adapting asexual populations, and conclude that linked beneficial mutations have a stronger influence on mutator fixation than the deleterious mutations.