A minimal scenario for the origin of non-equilibrium order (2405.10911v3)

Abstract: Life uses non-equilibrium mechanisms to create ordered structures not attainable at equilibrium; the resulting order is assumed to provide functional benefits that outweigh costs of time and energy needed by these mechanisms. Here, we show that models of DNA replication and self-assembly, when expanded to include known stalling effects, can evolve error correcting mechanisms like kinetic proofreading and dynamic instability through selection for fast replication alone. We abstract these results into a general framework that predicts a counterintuitive ''order through speed'' effect if the distribution of replication times is wide enough. We test our results against recent mutational screens of proofreading polymerases. Our work suggests the intriguing possibility that non-equilibrium order can evolve even before that order is directly functional, with consequences for the evolution of mutation rates, viral capsid assembly, and the origin of life.

• The paper demonstrates that selection for rapid replication can unintentionally foster dissipative, order-enhancing mechanisms in self-replicating systems.
• The authors extend polymerase models to include stalling effects, revealing a trade-off between replication speed and fidelity supported by mutagenesis data.
• The study proposes that mechanisms akin to Maxwell demons operate in high-dimensional state spaces, reducing error and enhancing structured outcomes.

Non-equilibrium Order in Biological Systems: The Interplay between Self-replication, Speed, and Dissipative Mechanisms

The research conducted by Ravasio et al. investigates the conditions under which non-equilibrium mechanisms capable of creating organized structures can emerge as a consequence of self-replication, rather than through selection for their direct functionality. The authors contend that various non-equilibrium order-creating processes, such as kinetic proofreading in biological replication and dynamic instability in self-assembly, can evolve primarily through selection for fast replication, even when the order does not offer a direct fitness benefit.

Theoretical Framework and Polymerase Kinetics

The paper presents a framework predicting that self-replicative systems tend to amplify dissipative order-enhancing mechanisms, provided the distribution of replication times is sufficiently broad. By expanding models of polymerases to incorporate stalling effects, the authors demonstrate that kinetic proofreading can evolve due to the selection pressure for rapid replication. This supports an alternate scenario where order in biological systems arises unintentionally as a byproduct of adaptive pressures on replication speed rather than through direct selection for order.

In their investigation of polymerase behavior, Ravasio et al. identify a counter-intuitive trade-off between replication speed and fidelity. Through in silico evolutionary experiments, they show that when DNA polymerases are selected for speed, higher fidelity can be achieved spontaneously through increased dissipative activities, such as kinetic proofreading. This phenomenon is attributable to the stalling effect intrinsic to polymerase function, whereby erroneous nucleotide incorporations extend the replication time, thereby favoring mechanisms that reduce these stalls.

Empirical Application and Mutagenesis Data

Within their empirical analysis, the authors reference mutational screens of DNA polymerase variants, providing evidence of speed-fidelity trade-offs in practical settings. Notably, the analysis of a large dataset from polymerase mutagenesis supports the notion that variants exhibiting faster replication rates tend to have lower error rates, corroborating theoretical predictions.

Self-assembly and Non-equilibrium Dynamics

Ravasio et al. extend their model to the self-assembly processes critical in cellular and sub-cellular architecture development, such as ribosomal assembly or viral capsid formation. By integrating a model of dynamic instability akin to microtubule behavior, they emphasize that systems selected for rapid assembly, but not necessarily precision, can evolve to demonstrate increased order and reduced errors.

In simulated evolution scenarios, structures that evolved under constraints of rapid assembly alone showed increased dynamic instability, leading to quicker turnover of misconstructed components. In practice, this translates to higher order and reduced variance in structural assembly outcomes, revealing a pathway by which complexity and error correction in biological systems might arise unselected for direct functionality.

High-dimensional Trajectories and Non-equilibrium Order

A critical insight from the paper is the presentation of a conceptual model where replication processes navigate high-dimensional state spaces. The authors propose that fast replication selects for mechanisms akin to Maxwell demons that irreversibly reset the system to starting conditions, thereby reducing trajectory entropy and facilitating greater order. This mechanism underscores a broader principle seen across various biological contexts: the emergence of order from constraints designed initially to enhance replication efficiency.

Implications for Evolution and Biological Systems

Conclusively, this research suggests that the evolution of non-equilibrium order in biological systems is more accessible than previously assumed and can occur as a secondary consequence of selection pressures on replication dynamics. The insights extend beyond theoretical implications, offering potential applications in understanding mutation rates, enzyme specificity in synthesis, and mechanisms of error reduction in biological systems. Moreover, the framework can inform synthetic biological endeavors aiming to engineer systems with high fidelity and rapid replication without the immediate necessity for artificially constructed order.

Thus, this investigation into the spontaneous emergence of order through selection on replication speed paradigms challenges conventional theories of biological complexity and provides a lens through which the evolution of cellular machinery can be understood.