An RNA condensate model for the origin of life

TL;DR

This paper proposes a model where RNA condensates could have served as self-replicating units in early life, addressing key origin-of-life questions and suggesting testable predictions based on recent experimental findings.

Contribution

The paper introduces a novel condensate-based model for RNA self-replication, linking phase separation with early molecular evolution and providing a framework for future experimental validation.

Findings

RNA condensates can catalyze templated polymerization.

Sequence-dependent condensate properties enable natural selection.

The model explains compartmentalization and error thresholds in early RNA evolution.

Abstract

The RNA World hypothesis predicts that self-replicating RNAs evolved before DNA genomes and coded proteins. Despite widespread support for the RNA World, self-replicating RNAs have yet to be identified in a natural context, leaving a key 'missing link' for this explanation of the origin of life. Inspired by recent work showing that condensates of charged polymers are capable of catalyzing chemical reactions, we consider a catalytic RNA condensate as a candidate for the self-replicating RNA. Specifically, we propose that short, low-complexity RNA polymers formed catalytic condensates capable of templated RNA polymerization. Because the condensate properties depend on the RNA sequences, RNAs that formed condensates with improved polymerization and demixing capacity would be amplified, leading to a 'condensate chain reaction' and evolution by natural selection. Many of the needed properties of this self-replicating RNA condensate have been realized experimentally in recent studies and our predictions could be tested with current experimental and theoretical tools. Our theory addresses central problems in the origins of life: (i) the origin of compartmentalization, (ii) the error threshold for the accuracy of templated replication, (iii) the free energy cost of maintaining an information-rich population of replicating RNA polymers. Furthermore, we note that the extant nucleolus appears to satisfy many of the requirements of an evolutionary relic for the model we propose. More generally, we suggest that future work on the origin of life would benefit from condensate-centric biophysical models of RNA evolution.