Error thresholds for self- and cross-specific enzymatic replication

TL;DR

This paper analyzes how enzymatic recognition specificity influences the ability to maintain genetic information and complexity in replicating systems, revealing that even weak specificity can stabilize populations and that stronger specificity allows longer recognition sequences.

Contribution

It introduces an idealized quasispecies model to study the effects of self- and cross-specific recognition on enzymatic replication stability and information retention.

Findings

Weak self-specificity suffices for population localization.

Stronger specificity allows longer recognition sequences.

Cross-specific localization is more challenging.

Abstract

The information content of a non-enzymatic self-replicator is limited by Eigen's error threshold. Presumably, enzymatic replication can maintain higher complexity, but in a competitive environment such a replicator is faced with two problems related to its twofold role as enzyme and substrate: as enzyme, it should replicate itself rather than wastefully copy non-functional substrates, and as substrate it should preferably be replicated by superior enzymes instead of less-efficient mutants. Because specific recognition can enforce these propensities, we thoroughly analyze an idealized quasispecies model for enzymatic replication, with replication rates that are either a decreasing (self-specific) or increasing (cross-specific) function of the Hamming distance between the recognition or "tag" sequences of enzyme and substrate. We find that very weak self-specificity suffices to localize a population about a master sequence and thus to preserve its information, while simultaneous localization about complementary sequences in the cross-specific case is more challenging. A surprising result is that stronger specificity constraints allow longer recognition sequences, because the populations are better localized. Extrapolating from experimental data, we obtain rough quantitative estimates for the maximal length of the recognition or tag sequence that can be used to reliably discriminate appropriate and infeasible enzymes and substrates, respectively.