Scientists Demonstrate Darwinian Evolution in Synthetic Self-Replicating Systems with Light-Driven Catalysis

Evolutionary Breakthrough in Synthetic Biology

Scientists have reportedly achieved a significant milestone in synthetic biology by creating self-replicating molecules that undergo Darwinian evolution based on their photocatalytic performance, according to research published in Nature Catalysis. The study demonstrates how synthetic systems can be designed to exhibit selection for protometabolic activity through fundamental evolutionary principles.

Evolutionary Breakthrough in Synthetic Biology
Engineering Evolutionary Systems
Molecular Mechanism and Cofactor Activation
Precursor Binding and Selective Advantage
Creating Mutant Replicator Systems
Out-of-Equilibrium Selection Experiments
Implications for Understanding Evolution

Engineering Evolutionary Systems

The research team developed a system where synthetic replicators compete under controlled conditions, with selection favoring those with superior photocatalytic capabilities. Sources indicate the design involved multiple critical steps: identifying a suitable protometabolic system, confirming selective binding of precursors to their producer replicators, creating replicator mutants with varying activities, and establishing out-of-equilibrium experiments that enable natural selection.

Analysts suggest this approach represents a sophisticated implementation of evolutionary principles in synthetic systems. “The design allows replicators responsible for producing precursors to selectively benefit from this activity, creating the conditions necessary for Darwinian evolution,” the report states regarding the experimental framework.

Molecular Mechanism and Cofactor Activation

At the core of the system are self-replicators that recruit photocatalytic cofactors, specifically Thioflavin T (ThT), which becomes activated upon binding to replicator fibers. According to reports, when irradiated, this cofactor produces singlet oxygen that converts thiol building blocks into disulfide-linked precursors essential for replication.

The research team found that ThT fluorescence was substantially enhanced when bound to certain replicators, indicating more efficient activation. Under photoirradiation, oxygen production was significantly more efficient in replicator-ThT mixtures compared to controls, with building block oxidation occurring up to four times faster in optimal conditions.

Precursor Binding and Selective Advantage

Critical to the evolutionary process is ensuring that replicators benefiting from photocatalytic activity retain those advantages. Experiments using centrifugation and high-speed atomic force microscopy confirmed that newly generated precursors remain attached to the fibers that produced them. The short lifetime of singlet oxygen in water (~3.5 μs) reportedly prevents diffusion to neighboring fibers, maintaining the selective advantage for active replicators.

“For natural selection based on photocatalytic activity to be feasible, it’s essential that precursors generated by a specific fiber remain associated with it long enough to be used for self-replication,” the report states regarding the mechanism maintaining selective pressure.

Creating Mutant Replicator Systems

Researchers developed two primary approaches to generate mutant replicators with varying photocatalytic efficiencies. The first involved mixing building blocks that don’t readily coassemble into beta-sheets, creating replicators with different abilities to activate the ThT cofactor. The second strategy combined building blocks predisposed to beta-sheet formation with those inherently poor at forming such structures.

In the 2+3 system, mixing different building blocks produced both trimer and hexamer replicators, while the 1+4 system generated various hexamer mutants. Analysis revealed that hexamer-rich replicators were approximately 2.6-2.8 times faster at producing singlet oxygen than trimer-rich variants, creating the performance differential necessary for selection.

Out-of-Equilibrium Selection Experiments

The research team constructed flow systems to test evolutionary selection under non-equilibrium conditions. Replicator systems were placed in continuous stirred tank reactors with constant inflow of building blocks and ThT, and outflow representing replicator “death.” The reactors were irradiated with flow rates maintaining constant volume and concentration.

When ThT was used with mutant replicators from the 2+3 system, the steady-state composition favored hexamer replicators, which are better at promoting photocatalysis. Control experiments using Ru(bpy)3²⁺, which produces singlet oxygen without binding to fibers, yielded completely different steady-state compositions dominated by trimers.

Implications for Understanding Evolution

These findings demonstrate that natural selection for protometabolic activity can favor replicators with higher molecular complexity over inherently faster-replicating but less complex variants, provided the more complex replicator has superior protometabolic activity. According to analysts, this observation complements earlier work where replicator complexification was achieved through thermophoresis or chemical fueling.

The research reportedly provides a framework for understanding how molecular complexity might have emerged in early evolutionary systems and opens new avenues for designing functional materials that evolve toward desired properties through fundamental evolutionary principles.