通过易错复制和选择从单个RNA序列中产生ATP和GTP结合适体

IF 3.1 Q2 CHEMISTRY, MULTIDISCIPLINARY ChemSystemsChem Pub Date : 2023-06-05 DOI:10.1002/syst.202300006
Dr. Falk Wachowius, Dr. Benjamin T. Porebski, Dr. Christopher M. Johnson, Dr. Philipp Holliger
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摘要

从不同的RNA序列池中自发产生的功能被广泛认为是生命起源的一个重要转变。在这里,我们表明多样化的序列池并不是功能出现的先决条件。我们从单个RNA种子序列开始了五个独立的选择实验,每个选择实验都包括一个中心的同源聚a(或聚u)片段,两侧是不同的保守引物结合位点。我们观察到种子通过突变、截断和重组转化(连续漂移)到低多样性序列库,即使在24轮之后也没有达到随机序列库的水平。经过连续的错误复制和ATP结合的选择,我们分离出具有低微摩尔亲和力的特异性ATP或gtp结合适体。我们的研究结果对早期RNA进化具有启示意义,因为与非酶和酶促益生元RNA复制相关的高突变率。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

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Emergence of ATP- and GTP-Binding Aptamers from Single RNA Sequences by Error-Prone Replication and Selection**

The spontaneous emergence of function from diverse RNA sequence pools is widely considered an important transition in the origin of life. Here we show that diverse sequence pools are not a prerequisite for the emergence of function. Starting five independent selection experiments each from a single RNA seed sequence - comprising a central homopolymeric poly-A (or poly-U) segment flanked by different conserved primer binding sites - we observe transformation (continuous drift) of the seeds into low diversity sequence pools by mutation, truncation and recombination without ever reaching that of a random pool even after 24 rounds. Upon continuous error prone replication and selection for ATP binding we isolate specific ATP- or GTP-binding aptamers with low micromolar affinities. Our results have implications for early RNA evolution in the light of the high mutation rates associated with both non-enzymatic and enzymatic prebiotic RNA replication.

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