Evolution of enzyme levels in metabolic pathways: A theoretical approach. Part 2

Abstract

Metabolism is essential for cell function and adaptation. Because of their central role in metabolism, kinetic parameters and enzyme concentrations are under constant selective pressure to adapt the fluxes of the metabolic networks to the needs of the organism. In line with various studies dealing with enzyme evolution, we recently developed a model of the evolution of enzyme concentrations under selection for increased flux, considered as a proxy for fitness (Coton et al., 2022). With this model, taking into account two realistic cellular constraints, competition for resources and co-regulation, we determined the evolutionary equilibria and range of neutral variations of enzyme concentrations. In this article, we expanded this model by considering that the enzymes in a pathway can belong to different co-regulation groups. We determined the equilibria and showed that the constraints modify the adaptive landscape by limiting the number of independent dimensions. We also showed that any trade-off between enzyme concentrations is sufficient to limit the flux and relax selection for increasing the concentration of other enzymes. Even though this model is based on simplifying assumptions, the complexity of the relationship between enzyme concentrations prevents the formal analysis of the range of neutral variation of enzyme concentrations. However, we could show that selection for maximizing the flux results in selective neutrality for all enzymes regardless the constraints applied, giving generality to the prediction of Hartl et al. (1985).

Keywords: Adaptive landscape; Co-regulation; Enzyme concentration; Evolutionary equilibrium; Selective neutrality.