A trade-off between neutrality and adaptability limits the optimization of viral quasispecies.

Theoretical studies of quasispecies usually focus on two properties of those populations at the mutation-selection equilibrium, namely asymptotic growth rate and population diversity. It has been postulated that, as a consequence of the high error rate of quasispecies replication, an increase of neutrality facilitates population optimization by reducing the amount of mutations with a deleterious effect on fitness. In this study we analyse how the optimization of equilibrium properties is affected when a quasispecies evolves in an environment perturbed through frequent bottleneck events. By means of a simple model we demonstrate that high neutrality may be detrimental when the population has to overcome repeated reductions in the population size, and that the property to be optimized in this situation is the time required to regenerate the quasispecies, i.e. its adaptability. In the scenario described, neutrality and adaptability cannot be simultaneously optimized. When fitness is equated with long-term survivability, high neutrality is the appropriate strategy in constant environments, while populations evolving in fluctuating environments are fitter when their neutrality is low, such that they can respond faster to perturbations. Our results might be relevant to better comprehend how a minority virus could displace the circulating quasispecies, a fact observed in natural infections and essential in viral evolution.