Shaping early molecular live by physical selection pressures

We will only fully understand the origin of life when we can recreate it in the laboratory. I report on our latest progress in building an autonomous evolution machine. A first step towards molecular evolution is the assembly of RNA from single nucleotides. We found that a moderate temperature difference at an air-water interface is an ideal micro-reactor for this process. The fluctuating interface continuously forms new dry spots by evaporation, driving the ring-opening polymerization of 2',3'-cyclic nucleotides toward RNA strands [1] and their length selective accumulation [2], including sequence-dependent phase transitions [3], showing fast evolution for DNA model systems [4] and accumulating prebiotic molecules by a thermal subsurface network [5]. The reaction only required a moderate alkaline pH and operated in a wide range of temperatures (4-80°C). The propagation of information is critical. Under the same pH conditions as above, we found templated ligation of RNA strands with 2',3'-cyclic ends. We see that both the formation and ligation is enhanced by amino acids. Surprisingly, the interface setting also shows signatures of modern cell biology: RNA is encapsulated into vesicles when lipids are added [2]. Even the components of modern cells assemble at the interface: a highly diluted PURE system accumulated at the air-water interface, triggering the expression of proteins such as GFP. Thus, interfaces control a remarkable variety of key steps in the evolution of life, making us optimistic that a prebiotic evolutionary machine can be created in the laboratory sooner rather than later.[1] ChemSystemsChem doi.org/10.1002/syst.202200026 (2022)[2] Nature Chemistry, doi.org/10.1038/s41557-019-0299-5 (2019)[3] PNAS doi.org/10.1073/pnas.2218876120 (2023)[4] Nature Physics doi.org/10.1038/s41567-022-01516-z (2022)[5] Nature doi.org/10.1038/s41586-024-07193-7 (2024)