2026-03-04 シカゴ大学
＜関連情報＞
- https://news.uchicago.edu/story/uchicago-scientists-clock-driving-factor-evolution-error-correction
- https://www.science.org/doi/full/10.1126/science.adt1275
速度の必要性によるエラー訂正の進化 Evolution of error correction through a need for speed
Riccardo Ravasio, Kabir Husain, Constantine G. Evans, Rob Phillips, […] , and Arvind Murugan
Science Published:19 Feb 2026
Editor’s summary
Life expends substantial effort correcting errors introduced by the forces of disorder. Molecular machines, from polymerases to the ribosome, use elaborate proofreading schemes to double-check their work, reducing errors at the cost of time and energy. Such mechanisms may not evolve easily because they devote precious resources to fixing mistakes. However, mistakes themselves also impose a time penalty, an effect known as stalling. Ravasio et al. present a theoretical analysis showing that because of stalling, error-correction mechanisms can in fact evolve to accelerate biological processes. The researchers found experimental support for this conclusion across a wide range of systems, from genome replication to the assembly of complex molecular structures. —Di Jiang
Structured Abstract
INTRODUCTION
Multistep assembly processes in biology are prone to errors, and as a result, diverse error correction strategies have evolved. For example, polymerases can excise an incorrect nucleotide by proofreading, transcription complexes can backtrack, and incorrectly assembled partial structures can be disassembled before trying again. These error-correcting mechanisms take time, leading to the widely held view that increased accuracy comes at the inevitable cost of slower replication or assembly. Error-correcting mechanisms are therefore thought to have evolved because errors in sequence or assembly are so deleterious that they must be corrected despite the additional time it takes to correct them.
RATIONALE
Standard accounts of error correction have ignored a ubiquitous effect called stalling, in which an uncorrected error, for example, one that occurs during DNA replication, can markedly slow subsequent steps, even if later steps are correct. Stalling increases the time it takes to complete a replication cycle or an assembly process, in proportion to the frequency of errors and the magnitude of the stalling effect. We show that because of stalling, error correction can speed up replication and assembly processes, despite the time taken to correct errors. We propose that a selective pressure for speed alone can lead, under certain conditions, to the evolution of error-correcting mechanisms.
RESULTS
We first developed a model of kinetic proofreading that includes stalling so that we could compare the time cost of stalling with the time cost of proofreading. Both theoretical analyses and in silico evolution show that in stall-dominated regimes, proofreading yields a net time benefit. In this context, selection for speed alone leads to increased proofreading even when errors carry no direct penalty. We predicted a preference for dissipative error correction over simpler reversible mechanisms. Second, we asked whether real biological systems satisfy these conditions. We found that stalling is widespread, from nonenzymatic and ribozyme-based replication to complex DNA and RNA polymerases, and is generally stronger in the latter. Experimental results on extensive mutagenesis of a DNA polymerase, spanning orders of magnitude in error rate and a proxy for activity, are consistent with speed selection that favors increased proofreading. Third, we generalized beyond templated replication to multicomponent assembly. Here, we found that selecting for faster assembly favors the evolution of disassembly mechanisms. These disassembly mechanisms are a by-product of a need for speed and serve to clear kinetically trapped intermediates.
CONCLUSION
In typical biological settings where accuracy is also under selection, our results predict that error-correcting mechanisms evolve more readily than expected because they confer a speed advantage rather than a time cost. This coupling can explain continued error-rate declines below that needed to maintain a genome of a given size, implying a complexity ratchet. Preexisting error correction allows genomes to increase further in size and thereby encode additional functions. This principle likely extends beyond central-dogma enzymes to the assembly of complex molecular machines and to other processes where errors slow the completion of a task.
Error correction evolves from a selection for speed.
(Left) Many biological systems fix mistakes by going backward, such as proofreading during DNA replication or reassembling macromolecular complexes. These corrections cost time. (Center) Without correction, mistakes cause long stalls; slow error-correcting systems end up finishing first. (Right) Under selection for faster completion alone (blue), evolution drives biology to a trade-off front (black) dictated by stalling, where gaining speed requires evolving error correction. t, time.
Abstract
Kinetic proofreading is a class of error-correcting mechanisms in biology that expend energy to avoid mistakes during replication, transcription, and translation. Proofreading is typically assumed to evolve when selection for fidelity outweighs costs in energy and the speed of replication. We show that when stalling after misincorporations is accounted for, proofreading can instead speed up replication. Consistent with data on polymerase mutagenesis, our results suggest that proofreading can evolve under selection for speed alone. We generalize to multicomponent self-assembly and show that analogous error-correcting processes, such as dynamic instability, can likewise emerge purely from selection for rapid assembly. Thus, nonequilibrium error correction can evolve from selection for speed, even without direct fidelity advantages. We discuss implications for mutation-rate evolution, molecular assembly processes, and models of early life.
