One of science’s greatest challenges is determining how life can spontaneously emerge from a mixture of molecules. A complicating factor is that life and its molecules are inherently unstable—RNA and proteins are prone to hydrolysis and denaturation. For the de novo synthesis of life or to better understand its emergence at its origin, selection mechanisms are needed for unstable molecules. Here we present a chemically fuelled dynamic combinatorial library to model RNA oligomerization and deoligomerization and shine new light on selection and purification mechanisms under kinetic control. In the experiments, oligomers can only be sustained by continuous production. Hybridization is a powerful tool for selecting unstable molecules, offering feedback on oligomerization and deoligomerization rates. Moreover, we find that templation can be used to purify libraries of oligomers. In addition, template-assisted formation of oligomers within coacervate-based protocells changes its compartment’s physical properties, such as their ability to fuse. Such reciprocal coupling between oligomer production and physical properties is a key step towards synthetic life.

科学面临的最大挑战之一是确定生命如何从分子混合物中自发地产生。一个复杂的因素是生命及其分子本质上不稳定——RNA 和蛋白质容易水解和变性。为了生命的从头合成或更好地理解生命的起源，需要不稳定分子的选择机制。在这里，我们提出了一个化学驱动的动态组合库来模拟 RNA 寡聚和去寡聚，并为动力学控制下的选择和纯化机制提供了新的线索。在实验中，低聚物只能通过连续生产来维持。杂交是选择不稳定分子的强大工具，可提供寡聚和去寡聚速率的反馈。此外，我们发现模板可用于纯化寡聚物文库。此外，基于凝聚层的原始细胞内模板辅助形成的寡聚物改变了其隔室的物理特性，例如它们的融合能力。低聚物生产和物理性质之间的这种相互耦合是迈向合成生命的关键一步。