Systems Biophysics and Center for NanoScience, Ludwigs-Maximilian-Universität München, 80799 Munich, Germany.
Center for Functional Nanomaterials, Brookhaven National Laboratory, Upton, NY 11973.
Proc Natl Acad Sci U S A. 2021 Feb 23;118(8). doi: 10.1073/pnas.2018830118.
The central question in the origin of life is to understand how structure can emerge from randomness. The Eigen theory of replication states, for sequences that are copied one base at a time, that the replication fidelity has to surpass an error threshold to avoid that replicated specific sequences become random because of the incorporated replication errors [M. Eigen, 58 (10), 465-523 (1971)]. Here, we showed that linking short oligomers from a random sequence pool in a templated ligation reaction reduced the sequence space of product strands. We started from 12-mer oligonucleotides with two bases in all possible combinations and triggered enzymatic ligation under temperature cycles. Surprisingly, we found the robust creation of long, highly structured sequences with low entropy. At the ligation site, complementary and alternating sequence patterns developed. However, between the ligation sites, we found either an A-rich or a T-rich sequence within a single oligonucleotide. Our modeling suggests that avoidance of hairpins was the likely cause for these two complementary sequence pools. What emerged was a network of complementary sequences that acted both as templates and substrates of the reaction. This self-selecting ligation reaction could be restarted by only a few majority sequences. The findings showed that replication by random templated ligation from a random sequence input will lead to a highly structured, long, and nonrandom sequence pool. This is a favorable starting point for a subsequent Darwinian evolution searching for higher catalytic functions in an RNA world scenario.
生命起源的核心问题是理解结构如何从随机性中涌现。复制的 Eigen 理论指出,对于一次复制一个碱基的序列,复制保真度必须超过误差阈值,以避免由于复制错误而导致复制的特定序列变得随机[M. Eigen,58(10),465-523(1971)]。在这里,我们表明,在模板连接反应中从随机序列池中连接短寡核苷酸会减少产物链的序列空间。我们从具有所有可能组合的两个碱基的 12 -mer 寡核苷酸开始,并在温度循环下触发酶促连接。令人惊讶的是,我们发现了具有低熵的长且高度结构化序列的稳健创建。在连接位点处,互补和交替的序列模式发展起来。然而,在连接位点之间,我们发现单个寡核苷酸内要么是 A 丰富的,要么是 T 丰富的序列。我们的模型表明,避免发夹结构可能是这两个互补序列库的原因。出现的是一个互补序列网络,它既作为反应的模板,也作为反应的底物。这种自选择的连接反应可以仅由少数多数序列重新启动。研究结果表明,从随机序列输入的随机模板连接进行复制将导致高度结构化、长且非随机的序列库。这是在 RNA 世界场景中寻找更高催化功能的后续达尔文进化的有利起点。