16.–18. Juli 2025
Online
Europe/Berlin Zeitzone

Non-enzymatic RNA Replication in Protocells

18.07.2025, 13:00
30m
Online

Online

Sprecher

Paul Higgs (McMaster University)

Beschreibung

RNA replication can occur inside lipid vesicles driven by activated nucleotides entering through the membrane. We study this using computational models. A metabolism is an autocatalytic reaction that maintains itself in a non-equilibrium state inside a cell while the outside environment remains inactive. We call this requirement inside-outside stability. We demonstrate that some forms of autocatalytic reactions satisfy this requirement, but we do not know of real small-molecule chemical systems that fit these reaction schemes. However, we show that templating of RNA oligomers in a protocell satisfies the required stability conditions. Hence RNA replication is itself a metabolism, and we do not need another (hypothetical) metabolism to drive RNA replication. Base sequences arising in oligomer templating tend to collapse into simple patterns with short repeats such as the combination of poly-A plus poly-U, or repeated AU, or many others. We identify all possible patterns that can exist and show that transitions occur from patterned states to random sequences as the error rate is increased. Patterns can be described as irreducible sets of short words that allow continued synthesis of the same words without creating words not in the set. If we begin with an oligomer mixture that encodes a desired sequence (e.g. a ribozyme), the sequence information is usually lost due to a scrambling process that creates sequences not originally present. Sequence information is only retained if the original sequence is an irreducible set that does not scramble. Even if the error rate is zero or very small, scrambling occurs for most initial sequences, followed by collapse of the sequences to a irreducible set with a short repeat pattern. If the error rate is larger, sequences simply become randomized. These constraints make it very unlikely that a mixture of oligomers replicating non-enzymatically could encode sequences long enough to be functional ribozymes.

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