Elucidating interplay of speed and accuracy in biological error correction.

Abstract

One of the most fascinating features of biological systems is the ability to sustain high accuracy of all major cellular processes despite the stochastic nature of underlying chemical processes. It is widely believed that such low error values are the result of the error-correcting mechanism known as kinetic proofreading. However, it is usually argued that enhancing the accuracy should result in slowing down the process, leading to the so-called speed-accuracy trade-off. We developed a discrete-state stochastic framework that allowed us to investigate the mechanisms of the proofreading using the method of first-passage processes. With this framework, we simultaneously analyzed the speed and accuracy of the two fundamental biological processes, DNA replication and tRNA selection during the translation. The results indicate that these systems tend to optimize speed rather than accuracy, as long as the error level is tolerable. Interestingly, for these processes, certain kinetic parameters lay in the suboptimal region where their perturbations can improve both speed and accuracy. Additional constraints due to the energetic cost of proofreading also play a role in the error correcting process. Our theoretical findings provide a microscopic picture of how complex biological processes are able to function so fast with high accuracy.