(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
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
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 veteran, (he/him) 🖖🏻
