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Selection for Photocatalytic Function through Darwinian Evolution of Synthetic Self-Replicators

by Keith CowingAugust 19, 2024August 18, 2024

(A) Mechanism of self-assembly driven self-replication. Oxidation of a mixture of two building blocks generates a dynamic combinatorial library of macrocycles (precursors). Replication occurs upon assembly of a specific macrocycle (here the hexamer) into stacks, on the side of which reservoirs of precursor form from which the replicator stacks grow. Mechanical agitation allows exponential replication through an elongation-fragmentation cycle. (B) Mixed-buiding-block replicators were formed upon combining building blocks 1 with 4, yielding a distribution of hexamer replicator mutants, or 2 with 3, yielding a mixture of trimer and hexamer replicators. (C) Light-mediated protometabolism. Binding of a photoredox cofactor dye to the replicator fiber enhances the photo-induced production of singlet oxygen by the dye. Singlet oxygen then enhances the conversion of the dthiol building blocks into small-ring precursors, which bind to the fiber sides. (D) Setup for out-of-equilibrium selection of self-replicators. A binary mixture of building blocks and photoredox cofactor ThT is added continuously to a stirred reactor containing the corresponding replicators. Outflow implements an indiscriminate “death” process. When bound to the replicator fibers and irradiated, ThT produces singlet oxygen, photo-oxidizing the dithiol building blocks to form the disulfide precursors for the replicators, which then accumulate in reservoirs on the fiber sides. (E) Darwinian evolution of hexamer replicators made from 1 and 4 in the setup shown in panel C results in selection for the photocatalytically most active 1-rich mutants. Similar experiments starting from building blocks 2 and 3 yield competing trimer and hexamer replicators from which the photocatalytically most active hexamers are selected in the course of evolution. -- chemrxiv.org Credit: NASA

The onset of Darwinian evolution represents a key step in the transition of chemical systems into living ones.

Here, we show the emergence of Darwinian evolution in two systems of self-replicating molecules, where natural selection favors replicator mutants best capable of catalyzing the production of the precursors required for their own replication.

Such selection for protometabolic activity was observed in a system where trimer and hexamer replicators compete for common resources, as well as in a system of different hexamer replicator mutants. An out-of-equilibrium replication-destruction regime was implemented in a flow reactor, where replication from continuously supplied dithiol building blocks needs to keep up with “destruction” by outflow.

Selection occurred based on the ability of the mutants to activate a cofactor that photocatalytically produces singlet oxygen which, in turn, enhances the rate by which dithiol building blocks are converted into disulfide-based replicator precursors. Selection was based on a functional trait (catalytic activity) opening up Darwinian evolution as a tool for catalyst development.

This work functionally integrates self-replication with protometabolism and Darwinian evolution and marks a further advance in the de-novo synthesis of life.

Kai Liu, Omer Markovitch, Chris van Ewijk,Yari Katar Knelissen, Armin Kiani, Marcel Eleveld, Wouter H. Roos, Sijbren Otto

Selection for Photocatalytic Function through Darwinian Evolution of Synthetic Self-Replicators, chemrxiv.org

Astrobiology,

Keith Cowing

Explorers Club Fellow, ex-NASA Space Station Payload manager/space biologist, Away Teams, Journalist, Lapsed climber, Synaesthete, Na’Vi-Jedi-Freman-Buddhist-mix, ASL, Devon Island and Everest Base Camp... More by Keith Cowing