Self-Assembly of Informational Polymers by Templated Ligation

Abstract

The emergence of evermore complex entities from prebiotic building blocks is a key aspect of origins of life research. The RNA-world hypothesis posits that RNA oligomers known as ribozymes acted as the first self-replicating entities. However, the mechanisms governing the self-assembly of complex informational polymers from the shortest prebiotic building blocks were unclear. One open issue concerns the relation between concentration and oligonucleotide length, usually assumed to be exponentially decreasing. Here, we show that a competition of timescales in the self-assembly of informational polymers by templated ligation generically leads to nonmonotonic strand-length distributions with two distinct length scales. The first length scale characterizes the onset of a strongly nonequilibrium regime and is visible as a local minimum. Dynamically, this regime is governed by extension cascades, where the elongation of a “primer” with a short building block is more likely than its dehybridization. The second length scale appears as a local concentration maximum and reflects a balance between degradation and dehybridization of completely hybridized double strands in a heterocatalytic extension-reassembly process. Analytical arguments and extensive numerical simulations within a sequence-independent model allowed us to predict and control these emergent length scales. Nonmonotonic strand-length distributions confirming our theory were obtained in thermocycler experiments using random DNA sequences from a binary alphabet. Our work emphasizes the role of structure-forming processes already for the earliest stages of prebiotic evolution. The accumulation of strands with a typical length reveals a possible starting point for higher-order self-organization events that ultimately lead to a self-replicating, evolving system.