The long and short of templated copying

TL;DR

This paper explores the thermodynamics and kinetics of templated copying in biological systems, emphasizing the necessity of free energy input for accurate copying and analyzing it as a non-equilibrium information engine.

Contribution

It provides a thermodynamic and kinetic analysis of templated copying, highlighting the importance of energy input and the non-equilibrium nature of the process.

Findings

Copying accuracy is limited by thermodynamic bounds at infinite length.

Finite length copying involves kinetic barriers affecting accuracy.

Copying systems can be modeled as non-equilibrium steady states and information engines.

Abstract

Templated copying is the central operation by which biology produces complex molecules. Cells copy sequence information from DNA to RNA and on into proteins, which are the molecules responsible for the function and regulation of cellular systems. In the templated copying process the template catalyses the formation of a second molecule carrying the same sequence. Traditionally, people have ignored the separation of the template and copy at the end of the process, but separation is necessary and fundamentally changes the thermodynamics of the process. In general, creating an accurate polymer costs free energy. Omitting separation, this cost can be compensated for by the extra free energy released by "correct" copy/template bonds. Separation requires these bonds be broken, so true copying requires an input of free energy. Equally the fact that copy/template bonds are temporary means there is no thermodynamic bias towards accuracy, instead copying relies only on kinetic effects to promote accuracy. In general, transducing energy can only happen reversibly when the transduction process is quasistatic and time varying; something that cannot be true when you are relying on kinetic discrimination. Copying is a far from equilibrium process. This thesis explores the consequences of this observation. We start in the limit of infinite length copies where the costs of accuracy represent hard thermodynamic bounds and then moves to the finite length limit where these same limits can be understood as kinetic barriers. We then discuss copying systems as non-equilibrium steady states, which can be analysed as information engines moving free energy between out-of-equilibrium baths.