Sustainable replication and coevolution of cooperative RNAs in an artificial cell-like system


Cooperation among independently replicating molecules is a key phenomenon that allowed the development of complexity during the early evolution of life. Generally, this process is vulnerable to parasitic or selfish entities, which can easily appear and destroy such cooperation. It remains unclear how this fragile cooperation process appeared and has been sustained through evolution. Theoretical studies have indicated that spatial structures, such as compartments, allow sustainable replication and the evolution of cooperative replication, although this has yet to be confirmed experimentally. In this study, we constructed a molecular cooperative replication system, in which two types of RNA, encoding replication or metabolic enzymes, cooperate for their replication in compartments, and we performed long-term replication experiments to examine the sustainability and evolution of the RNAs. We demonstrate that the cooperative relationship of the two RNAs could be sustained at a certain range of RNA concentrations, even when parasitic RNA appeared in the system. We also found that more efficient cooperative RNA replication evolved during long-term replication through seemingly selfish evolution of each RNA. Our results provide experimental evidence supporting the sustainability and robustness of molecular cooperation on an evolutionary timescale.

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Fig. 1: Computer simulation of cooperative RNA replication.
Fig. 2: TcCRR system.
Fig. 3: Long-term replication experiments.
Fig. 4: Template and cooperation activity of the RNA clones in the replicating population.
Fig. 5: Cooperative replication assay of the evolved RNAs.


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We would like to thank N. Lehman, N. Takeuchi and T. Yomo for useful discussion and comments. This work was supported by JSPS KAKENHI grant numbers JP15KT0080 and JP15H04407.

Author information

R.M. designed and performed all experiments and wrote the manuscript. N.I. designed experiments and wrote the manuscript.

Correspondence to Norikazu Ichihashi.

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Supplementary Discussion; Supplementary Figures 1–9; Supplementary Tables 1–5; Supplementary References

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