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<p>Accurate propagation of sequence information in nucleic acids is central to the evolutionary dynamics of self-replicating systems. Modern biological systems achieve high fidelity using enzymes that actively correct errors through energy-driven mechanisms. However, such complex machinery was absent under prebiotic conditions. Here, we present a theoretical model of error correction in self-replicating heteropolymers that requires neither enzymes nor an extraneous energy supply. The model relies solely on the free-energy gradient driving strand growth and requires asymmetric cooperativity—a kinetic asymmetry known to promote unidirectional elongation. Despite its simplicity, we demonstrate that this minimal model facilitates kinetic discrimination between correct and incorrect base pair incorporations, and for specific set of parameters, reproduces the error ratio of <InlineEquation ID="IEq1"> <EquationSource Format="TEX">\(\sim 10^{-4}\)</EquationSource> </InlineEquation>, experimentally observed in passive base selection processes. It replicates key features observed in DNA error correction, including stalling, fraying, next-nucleotide effects, and the speed–accuracy trade-off. Our results provide plausible answers for longstanding questions, such as the energy source for the enhanced base selectivity of passive DNA polymerases and the role of thermodynamics and kinetics of phosphodiester bond formation in error correction. We show that catalysis of the phosphodiester bond plays a central role in error correction, even without explicit enzymatic structural discrimination. This observation points to a plausible pathway for accurate oligomer synthesis under prebiotic conditions, driven solely by the thermodynamic gradient favoring strand elongation. More broadly, the model highlights how persistent molecular order can emerge from non-equilibrium dynamics—a central requirement for emergence of life.</p>

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Non-enzymatic error correction in self-replicators without extraneous energy supply

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年2月22日

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  • Koushik Ghosh,
  • Parthasarthi Sahu,
  • Shashikanta Barik,
  • Hemachander Subramanian

摘要

Accurate propagation of sequence information in nucleic acids is central to the evolutionary dynamics of self-replicating systems. Modern biological systems achieve high fidelity using enzymes that actively correct errors through energy-driven mechanisms. However, such complex machinery was absent under prebiotic conditions. Here, we present a theoretical model of error correction in self-replicating heteropolymers that requires neither enzymes nor an extraneous energy supply. The model relies solely on the free-energy gradient driving strand growth and requires asymmetric cooperativity—a kinetic asymmetry known to promote unidirectional elongation. Despite its simplicity, we demonstrate that this minimal model facilitates kinetic discrimination between correct and incorrect base pair incorporations, and for specific set of parameters, reproduces the error ratio of \(\sim 10^{-4}\) , experimentally observed in passive base selection processes. It replicates key features observed in DNA error correction, including stalling, fraying, next-nucleotide effects, and the speed–accuracy trade-off. Our results provide plausible answers for longstanding questions, such as the energy source for the enhanced base selectivity of passive DNA polymerases and the role of thermodynamics and kinetics of phosphodiester bond formation in error correction. We show that catalysis of the phosphodiester bond plays a central role in error correction, even without explicit enzymatic structural discrimination. This observation points to a plausible pathway for accurate oligomer synthesis under prebiotic conditions, driven solely by the thermodynamic gradient favoring strand elongation. More broadly, the model highlights how persistent molecular order can emerge from non-equilibrium dynamics—a central requirement for emergence of life.