Salibi, EliaPeter, BenediktSchwille, PetraMutschler, Hannes2024-08-152024-08-152023-03-03http://hdl.handle.net/2003/4264810.17877/DE290R-24485Growth and division of biological cells are based on the complex orchestration of spatiotemporally controlled reactions driven by highly evolved proteins. In contrast, it remains unknown how their primordial predecessors could achieve a stable inheritance of cytosolic components before the advent of translation. An attractive scenario assumes that periodic changes of environmental conditions acted as pacemakers for the proliferation of early protocells. Using catalytic RNA (ribozymes) as models for primitive biocatalytic molecules, we demonstrate that the repeated freezing and thawing of aqueous solutions enables the assembly of active ribozymes from inactive precursors encapsulated in separate lipid vesicle populations. Furthermore, we show that encapsulated ribozyme replicators can overcome freezing-induced content loss and successive dilution by freeze-thaw driven propagation in feedstock vesicles. Thus, cyclic freezing and melting of aqueous solvents – a plausible physicochemical driver likely present on early Earth – provides a simple scenario that uncouples compartment growth and division from RNA self-replication, while maintaining the propagation of these replicators inside new vesicle populations.enNature communications;14https://creativecommons.org/licenses/by/4.0/Membrane biophysicsChemical origin of lifeRibozymesRNASynthetic biology570540Periodic temperature changes drive the proliferation of self-replicating RNAs in vesicle populationsArticle