Insights into Error Control Mechanisms in Biological Processes: Copolymerization and Enzyme-Kinetics Revisited.

The high fidelity observed in biological information processing ranging from replication to translation has stimulated significant research efforts to clarify the underlying microscopic picture. Theoretically, several approaches to analyze the error rates have been proposed. The copolymerization theory describes the addition and removal of monomers at the growing tip of a copolymer, leading to a closed set of nonlinear equations. On the other hand, enzyme-kinetics approaches formulate linear equations of biochemical networks, describing transitions between discrete chemical states. However, it is still unclear whether the error values computed by the two approaches agree. Moreover, there are conflicting interpretations on whether the error is under thermodynamic or kinetic discrimination control. In this work, we examine the error rate in persistent copying biochemical processes by specifically analyzing both theoretical approaches. The initial disagreement of the results between the two theories motivated us to rederive the formula for the error rate in the kinetic model. The error computed with the new method resulted in excellent agreement between both theoretical approaches and with Monte Carlo simulations. Furthermore, our theoretical analysis shows that the kinetic discrimination controls the error, even when the energy difference between adding the right and wrong products is very small. Our theoretical investigation gives important insights into the physical-chemical properties of complex biological processes by providing the quantitative framework to evaluate them.