Genetic complementation fosters evolvability in complex fitness landscapes

The ability of natural selection to optimize traits depends on the topology of the genotype-fitness map (fitness landscape). Epistatic interactions produce rugged fitness landscapes, where adaptation is constrained by the presence of low-fitness intermediates. Here, we used simulations to explore how evolvability in rugged fitness landscapes is influenced by genetic complementation, a process whereby different sequence variants can compensate for their deleterious mutations. We designed our model inspired by viral populations, in which genetic variants are known to interact frequently through coinfection. Our simulations indicate that genetic complementation enables a more efficient exploration of rugged fitness landscapes. Although this benefit may be undermined by genetic parasites, its overall effect on evolutionary fitness remains positive in populations that exhibit strong relatedness between interacting sequences. Similar processes could operate in contexts other than viral coinfection, such as in the evolution of ploidy.