Interaction between directional epistasis and average mutational effects

We investigate the relationship between the average fitness decay due to single mutations and the strength of epistatic interactions in genetic sequences. We observe that epistatic interactions between mutations are correlated to the average fitness decay, both in RNA secondary structure prediction as well as in digital organisms replicating in silico. This correlation implies that, during adaptation, epistasis and average mutational effect cannot be optimized independently. In experiments with RNA sequences evolving on a neutral network, the selective pressure to decrease the mutational load then leads to a reduction in the amount of sequences with strong antagonistic interactions between deleterious mutations in the population.