Recent research showed that an artificially constructed RNA self-replicating system modeling primitive life at the origin of life evolved to become more prone to extinction under certain experimental conditions.
Modern life is a complex assembly of numerous molecules with diverse functions. However, it is believed that when life first emerged in ancient times, simple molecules such as RNA and proteins appeared first. How such diverse functions and complexity arose from these replicating molecules remains a major mystery. To understand such evolutionary processes, evolutionary experiments, in which molecules are artificially evolved to simulate what might have occurred in the past, are an effective approach.
A research group led by Professor Norikazu Ichihashi of the University of Tokyo has previously conducted evolutionary experiments using RNA that replicates via proteins produced by itself, and revealed that parasites play a critical role in the evolution of replicating molecules. The term "parasite" here refers to RNA molecules that carry no protein-coding information but are amplified by proteins synthesized from host RNA. These parasitic RNAs emerged spontaneously during evolutionary experiments and competed with host RNAs, driving both hosts and parasites to diversify into multiple distinct types. This suggests that host-parasite competition may be a driving force in the evolution of replicators toward complexity. However, parasites inherently harm their hosts. Under what circumstances, then, do parasites act to increase molecular complexity?
In this study, the researchers transferred a subset of the RNA population from their previous manual evolutionary experiments to an automated flow reactor system. In the previous experiments, RNA diversified and replication remained stable even after more than 240 generations. In the new evolutionary experiment, however, the outcome was completely different: the original RNA diversity was lost, and as evolution progressed, RNA frequently went extinct.
What was different about this flow reactor experiment compared to the previous ones? Both experimental setups employed compartmentalization to allow hosts and parasites to coexist. A compartment is a small droplet suspended in oil, within which replication reactions occur; agitation causes compartments to fuse or divide, dispersing the molecules. In this way, when host RNA populations decline due to parasites, hosts can escape parasitic pressure by dispersing. The key difference between the two experimental setups lies in how these compartments are mixed.
In the previous experiments involving diversification, 20% of the total reaction volume was transferred to a new reaction vessel containing fresh reaction mixture every five hours. In contrast, the flow reactor continuously circulates the reaction mixture while gently stirring it, resulting in more frequent mixing of RNAs than in the previous setup.
This study showed that well-mixed environments inhibited host RNA replication, leading to both a decrease in RNA concentration and a loss of RNA diversity. Furthermore, this reduced concentration may have made host RNAs more susceptible to the accumulation of deleterious mutations through genetic drift. This in turn caused a further decrease in RNA concentration, ultimately resulting in extinction.
This study demonstrated that self-replicating RNAs evolve differently depending on the frequency of mixing, suggesting that the surrounding environment may determine their fate — whether they give rise to life or not. These findings point to new conditions that may have been required for the origin of life.
