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.
- Received 25 November 2020
- Revised 21 June 2021
- Accepted 25 June 2021
DOI:https://doi.org/10.1103/PhysRevX.11.031055
Published by the American Physical Society under the terms of the Creative Commons Attribution 4.0 International license. Further distribution of this work must maintain attribution to the author(s) and the published article’s title, journal citation, and DOI.
Published by the American Physical Society
Physics Subject Headings (PhySH)
Popular Summary
A key aim in origins-of-life research is to understand how self-replicating evolving systems can spontaneously emerge in nonequilibrium environments. Informational polymers such as RNA play pivotal roles as information carriers in these scenarios and, according to the “RNA world” hypothesis, also as the first functional molecules catalyzing reactions. However, it is not clear how RNA strands that are long enough to act as functional molecules came into being. Here, we show how competition of timescales in the self-assembly of RNA leads to strands with a distinct length scale.
To answer this question, the structure that is already induced by the growth of short informational polymers must be understood. Short informational polymers can grow via a process called templated ligation: Two strands bind (hybridize) next to each other on a third strand, the “template,” which enables the joining (ligation) of the two strands into one.
We studied how this growth process shapes the length distribution of informational polymers. Using stochastic simulations, we find that the process generally leads to a minimum and a maximum in the length distribution. The maximum constitutes a source of informational polymers of a specific length that can be tuned by changing physical parameters. As such, these strands can serve as the building blocks for a structure-forming process on longer-length scales.
How this structure-forming process affects the evolution in sequence space is an intriguing open question for future research.
