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. This model has been extensively compared with the parity model, in which the 2 mutation rates are equal under a constant mutation rate. In this study, we analyzed the evolution of two freely mutating mutation rates imported at the time of replication. In all trials, the difference between 2 mutation rates, the fidelity difference (FD), oscillated significantly above 0 during evolution as gene scores 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 mutation rate remained high while the other automatically decreased. Our results reveal that 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 evolution. This offers a new perspective on mutator hitchhiking in evolutionary biology.