Resource uptake and the evolution of moderately efficient enzymes

Abstract

Enzymes speed up reactions that would otherwise be too slow to sustain the metabolism of self-replicators. Yet, most enzymes seem only moderately efficient, exhibiting kinetic parameters orders of magnitude lower than their expected physically achievable maxima. Here, we question how these parameters evolve using a mechanistic model where enzyme efficiency is a key component of individual competition for resources. We show that kinetic parameters are under strong directional selection only up to a point, above which enzymes appear to evolve under near-neutrality. A majority of kinetic parameters compiled elsewhere do spread onto this plateau. Nonetheless, using a population genetics model that includes genetic drift and mutational biases, we show that this is a very unlikely outcome of evolution on a common landscape, as even very moderate biases towards lower efficiency should prevent the occurrence of such a diversity. Instead, differences between species, and within a species between metabolic pathways and the reactions to perform, should be involved. Our results point to drift playing an important role, along with the kinetics of nutrient transporters, the tolerance to high concentrations of intermediate metabolites, and the reversibility of reactions. Enzyme concentration also shapes selection on kinetic parameters, suggesting that the joint evolution of concentration and efficiency, facilitated by the plateau, should matter. Interestingly, the position of an enzyme along the metabolic pathway is not key for its evolution, contrasting with the prediction of models assuming that fitness depends on a precise level of flux control, rather than on competitive abilities.

Optimal enzyme utilization suggests concentrations and thermodynamics favor condition-specific saturations and binding mechanisms

“…It was previously suggested that although nearly optimal enzymes exist, most enzymes show moderate catalytic efficiencies and are far from catalytic perfection 32,33 . Most of these studies have focused on “composite” efficiency quantities to study the evolutionary pressure, neglecting the independent effect of each dimension on the evolutionary processes 43,44 . In this study, our analysis was focused and limited to the kinetic design and modes of operations of enzymes at maximal reaction-rates.…”

On the incongruence of genotype-phenotype and fitness landscapes

“…For example, fitness may depend upon more phenotypes than those being assayed 27 or the relationship between phenotype and fitness may be inherently nonlinear, for example reflecting a tradeoff between the costs and benefits associated with a phenotype 28 . In the latter case, selection may favor a low or intermediate phenotypic value 29,30 ; e.g., an intermediate gene expression level, [31][32][33] , enzyme efficiency 34 or protein production rate or activity 35 . Such non-linearities are a cause of epistasis 16,[36][37][38] , and they can transform the effects of mutations as they map onto phenotype and fitness 37 , thus rendering the topographical properties of a fitness landscape qualitatively different from those of its underlying genotype-phenotype landscape (Fig.…”