Metabolic trade-offs and the maintenance of the fittest and the flattest

Abstract

How is diversity maintained? Environmental heterogeneity is considered to be important¹, yet diversity in seemingly homogeneous environments is nonetheless observed². This, it is assumed, must either be owing to weak selection, mutational input or a fitness advantage to genotypes when rare¹. Here we demonstrate the possibility of a new general mechanism of stable diversity maintenance, one that stems from metabolic and physiological trade-offs³. The model requires that such trade-offs translate into a fitness landscape in which the most fit has unfit near-mutational neighbours, and a lower fitness peak also exists that is more mutationally robust. The ‘survival of the fittest’ applies at low mutation rates, giving way to ‘survival of the flattest’^4,5,6 at high mutation rates. However, as a consequence of quasispecies-level negative frequency-dependent selection and differences in mutational robustness we observe a transition zone in which both fittest and flattest coexist. Although diversity maintenance is possible for simple organisms in simple environments, the more trade-offs there are, the wider the maintenance zone becomes. The principle may be applied to lineages within a species or species within a community, potentially explaining why competitive exclusion need not be observed in homogeneous environments. This principle predicts the enigmatic richness of metabolic strategies in clonal bacteria⁷ and questions the safety of lethal mutagenesis^8,9 as an antimicrobial treatment.