Replication Fidelity Difference between Daughter Chains Persists during Evolution

While mutations are the engine of evolution, how mutation rates themselves evolve remains poorly understood. Previous simulation and experimental studies have often treated the mutation rate as a simple, cell-wide constant, an assumption that may not fully capture the asymmetric and dynamic nature of replication fidelity in living systems. The disparity mutagenesis model explains the conservation of replicated genetic information via unequal mutation rates and theoretically avoiding extinction due to intracellular damage. This model has been extensively compared with the parity model, in which the two mutation rates are equal under a constant mutation rate. In this study, we extended our investigation and analyzed the evolution of two freely mutating mutation rates that could vary between 0 and 1, and were imported at the time of replication using a simple simulation model. Our simulation imposed no constraints on the mutation rates and highlighted the a priori functionality of the mutation rate parameter. In all trials, the difference between two mutation rates, the fidelity difference (FD), oscillated significantly above 0 during evolution as gene scores, which function as fitness score, increased. After the total gene score reached a plateau, the FD remained constant and stabilized at two unequal mutation rates. The high average mutation rate indicated the generation of the 'genome guarantee effect' as one of the two mutation rates always remained high and the other automatically decreased. Our results reveal a crucial new insight: if a life form replicates with a doubling of genetic information, the FD never converges to zero and automatically remains in the disparity state throughout the evolutionary process. This offers a new perspective on the long-standing issue of mutator hitchhiking in evolutionary biology.