Ineffectual Genomic Error Correction Under Environmental Perturbation Dynamically Regulates Mutational Supply and...

Adaptation requires an adequate supply of heritable variation, yet too much mutation can limit organismal viability by disrupting essential molecular functions. Our study shows that this trade-off arises inherently from the kinetic proofreading mechanism that dictates the replication fidelity. In our model, environmental shifts alter the optimal driving rate constant of proofreading enzymes, transiently elevating replication error rates and triggering rapid evolutionary change until a new fidelity optimum is reached. This produces alternating periods of stasis and rapid adaptation, the central signature of punctuated equilibrium. We further show that coding-region length and population size jointly determine whether adaptation succeeds or mutational collapse occurs, reflecting the balance between mutation supply and error tolerance. The resulting limit on mutation rates is qualitatively consistent with predictions of the drift-barrier hypothesis. Therefore, evolution is shown to select a mutation rate that supports evolutionary adaptation while avoiding genomic meltdown.