Division Biological Physics, Max Planck Institute for the Physics of Complex Systems, Dresden 01187, Germany.
Center for Systems Biology Dresden, Dresden 01307, Germany.
Proc Natl Acad Sci U S A. 2023 Oct 24;120(43):e2218876120. doi: 10.1073/pnas.2218876120. Epub 2023 Oct 17.
The emergence of functional oligonucleotides on early Earth required a molecular selection mechanism to screen for specific sequences with prebiotic functions. Cyclic processes such as daily temperature oscillations were ubiquitous in this environment and could trigger oligonucleotide phase separation. Here, we propose sequence selection based on phase separation cycles realized through sedimentation in a system subjected to the feeding of oligonucleotides. Using theory and experiments with DNA, we show sequence-specific enrichment in the sedimented dense phase, in particular of short 22-mer DNA sequences. The underlying mechanism selects for complementarity, as it enriches sequences that tightly interact in the dense phase through base-pairing. Our mechanism also enables initially weakly biased pools to enhance their sequence bias or to replace the previously most abundant sequences as the cycles progress. Our findings provide an example of a selection mechanism that may have eased screening for auto-catalytic self-replicating oligonucleotides.
早期地球上功能性寡核苷酸的出现需要一种分子选择机制，以筛选具有前生物功能的特定序列。在这种环境中，周期性过程（如每日温度波动）无处不在，并且可以触发寡核苷酸相分离。在这里，我们提出了一种基于相分离循环的序列选择机制，该机制通过在一个向寡核苷酸供料的系统中进行沉降来实现。我们使用 DNA 的理论和实验表明，在沉降的密集相中会出现序列特异性富集，特别是在短的 22 -mer DNA 序列中。这种机制通过碱基配对选择互补性，因为它富集了在密集相中紧密相互作用的序列。我们的机制还使最初具有微弱偏向性的池能够增强其序列偏向性，或者随着循环的进行取代以前最丰富的序列。我们的研究结果提供了一个选择机制的例子，该机制可能有助于筛选自动催化自我复制的寡核苷酸。
