Catalytic promiscuity in the RNA World may have aided the evolution of prebiotic metabolism

Author summary Complex biochemical machineries responsible for maintaining the correct ratio of enzymes and genes were highly unlikely to exist at the wake of life. Individual genes must have been subject to competition for resources of replication leading to the competitive exclusion between them, and thus to the loss of genetic information. A feasible scenario that avoids competitive exclusion requires the assumption of mandatory cooperation between the enzymes. A potentially dynamically important but mostly neglected feature of RNA enzymes (ribozymes) is their capacity to catalyse more than a single reaction. Here, we analyse the possibility that this "promiscous" nature of prebiotic ribozymes could have helped the maintenance of early replicator communities cooperating in running a simple metabolism. To do so, we have implemented a spatially explicit computer model simulating the dynamics of replicating entities on a mineral surface-an extension of the Metabolically Coupled Replicator System including the possibility of multiple catalytic activities within the same replicator. Our results suggest that under realistic assumptions of replicator and metabolite mobility and feasible trade-off relations between different catalytic activities of the same RNA replicator molecule, catalytic promiscuity may have indeed helped booting up life through supporting the assembly of minimal metabolisms. The Metabolically Coupled Replicator System (MCRS) model of early chemical evolution offers a plausible and efficient mechanism for the self-assembly and the maintenance of prebiotic RNA replicator communities, the likely predecessors of all life forms on Earth. The MCRS can keep different replicator species together due to their mandatory metabolic cooperation and limited mobility on mineral surfaces, catalysing reaction steps of a coherent reaction network that produces their own monomers from externally supplied compounds. The complexity of the MCRS chemical engine can be increased by assuming that each replicator species may catalyse more than a single reaction of metabolism, with different catalytic activities of the same RNA sequence being in a trade-off relation: one catalytic activity of a promiscuous ribozyme can increase only at the expense of the others on the same RNA strand. Using extensive spatially explicit computer simulations we have studied the possibility and the conditions of evolving ribozyme promiscuity in an initial community of single-activity replicators attached to a 2D surface, assuming an additional trade-off between replicability and catalytic activity. We conclude that our promiscuous replicators evolve under weak catalytic trade-off, relatively strong activity/replicability trade-off and low surface mobility of the replicators and the metabolites they produce, whereas catalytic specialists benefit from very strong catalytic trade-off, weak activity/replicability trade-off and high mobility. We argue that the combination of conditions for evolving promiscuity are more probable to occur for surface-bound RNA replicators, suggesting that catalytic promiscuity may have been a significant factor in the diversification of prebiotic metabolic reaction networks.