Effect of Co-solutes on Template-Directed Nonenzymatic Replication of Nucleic Acids

The widely acknowledged 'RNA world' theory pertains to how life might have chemically originated on early Earth. It presumes the existence of catalytic RNAs, which were also capable of storing and propagating genetic information. Substantial research has gone into understanding how enzyme-free reactions of nucleic acids might have led to the formation of such catalytic RNA polymers. However, most of these studies involved reactions that were performed in aqueous systems devoid of any "background" molecules. This scenario is not a true representation of the complex chemical environment that might have been prevalent on prebiotic Earth. In the present study, we analyzed the effect of co-solutes ("background" molecules) on the rate and accuracy of template-directed nonenzymatic replication of RNA, in a putative RNA world. Our results suggest that presence of co-solutes in the reaction affects the addition of purine monomers across their cognate template base. Reduction in the rate of these 'fast' cognate addition reactions resulted in an apparent increase in the frequency of mismatches in the presence of co-solutes. However, reactions that involved the addition of a mismatched base were not notably affected. Such a scenario could have led to an accrual of mutations during the propagation of functional sequences on early Earth, unless the relevant sequences were separated from the bulk reaction milieu by some limiting boundary structure (e.g., a membrane). In general, our results suggest that the presence of co-solutes could have affected certain prebiotic reaction rates to a larger extent than others. Even modest changes in nonenzymatic replication reaction rates could have eventually resulted in the accumulation of greater variation in RNA sequences over prolonged time periods. It, therefore, is pertinent to account for the chemical complexity intrinsic to prebiotic environments while studying relevant nonenzymatic reactions.