Experimental demonstration of kinetic proofreading inherited in ligation-based information replication

TL;DR

This study experimentally shows that ligation-based DNA replication employs a kinetic proofreading mechanism, significantly reducing errors especially in longer strands, with implications for prebiotic chemistry and biotechnology.

Contribution

It demonstrates experimentally that ligation-based DNA replication inherits kinetic proofreading, providing a new understanding of error suppression mechanisms in molecular replication.

Findings

Longer DNA strands have lower error rates.

Ligation-based replication outperforms polymerization in error suppression.

The mechanism suggests a route for high-fidelity prebiotic replication.

Abstract

We experimentally demonstrate that information replication by templated ligation of DNA strands inherits a kinetic proofreading mechanism and achieves significant error suppression through cascade replication. A simple simulation model derived from the experimental results shows that templated ligation has a significant advantage over replication by polymerization for error suppression of long strands. Specifically, longer chains show lower error rates, significantly distinct from the chain-growth polymerization where errors typically accumulate with chain length. This mechanism provides a plausible route for high-fidelity replication in prebiotic chemistry and illustrates how physical principles such as nonequilibrium kinetics and network architecture can drive reliable molecular information replication. The approach also offers new strategies for error suppression in biotechnology.