When proofreading improves both speed and accuracy

Abstract

Proofreading is generally thought to improve accuracy at the expense of speed. We show that this trade-off can be reversed in stochastic processes with long-lived stalled states. Using a non-Markovian renewal framework, we derive exact expressions for the error rate and completion time under proofreading for arbitrary stall-time distributions. Our analysis reveals that fluctuations in stall durations, rather than their mean alone, determine whether proofreading can simultaneously increase speed and accuracy. In the limit of strong stalling, this regime emerges when the coefficient of variation of the stall time exceeds a threshold set by the intrinsic error rate. These results provide a general criterion for proofreading in systems ranging from self-assembly and polymer replication to immune recognition and other nonequilibrium information-processing systems.