The evolution of non-equilibrium error-correction in biology

Life today relies on numerous baroque mechanisms to maintain order: keeping itself far from the inanimate state of thermal equilibrium. Yet, while we understand how these mechanisms work, much less is known about how they come into existence in the first place. Here, we suggest that surprisingly little might be needed. We study the copying of information in different classes of biological macromolecules. In each, fast replication alone selects for the evolution of non-equilibrium error-correction. Our results rely only on geometric frustration effects intrinsic to the physics of multicomponent assembly. To test the theory, we develop a massively multiplexed Luria-Delbruck assay in yeast, capable of measuring thousands of mutation rates in a single experiment.  Overall, our work sheds light on the origins of fidelity in biomolecular processes, and highlights the role of biophysical constraints in shaping the parameters of evolution.

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