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Error thresholds for RNA replication in the presence of both point mutations and premature termination errors

机译:在存在两点突变和过早终止错误的情况下RNA复制的误差阈值

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摘要

We consider a spatial model of replication in the RNA World in which polymerase ribozymes use neighbouring strands as templates. Point mutation errors create parasites that have the same replication rate as the polymerase. We have shown previously that spatial clustering allows survival of the polymerases as long as the error rate is below a critical error threshold. Here, we additionally consider errors where a polymerase prematurely terminates replication before reaching the end of the template, creating shorter parasites that are replicated faster than the functional polymerase. In well-known experiments where Q beta RNA is replicated by an RNA polymerase protein, the virus RNA is rapidly replaced by very short nonfunctional sequences. If the same thing were to occur when the polymerase is a ribozyme, this would mean that termination errors could potentially destroy the RNA World. In this paper, we show that this is not the case in the RNA replication model studied here. When there is continued generation of parasites of all lengths by termination errors, the system can survive up to a finite error threshold, due to the formation of travelling wave patterns; hence termination errors are important, but they do not lead to the inevitable destruction of the RNA World by short parasites. The simplest assumption is that parasite replication rate is inversely proportional to the strand length. In this worst-case scenario, the error threshold for termination errors is much lower than for point mutations. We also consider a more realistic model in which the time for replication of a strand is the sum of a time for binding of the polymerase, and a time for polymerization. When the binding step is considered, termination errors are less serious than in the worst case. In the limit where the binding time is dominant, replication rates are equal for all lengths, and the error threshold for termination is the same as for point mutations. (C) 2017 Elsevier Ltd. All rights reserved.
机译:我们考虑RNA世界中复制的空间模型,其中聚合酶核酶使用相邻的股线作为模板。点突变误差产生具有与聚合酶相同的复制率的寄生虫。我们以前所示的空间聚类允许聚合酶的存活,只要误差率低于临界误差阈值即可。这里,我们还考虑在到达模板结束前过早地终止复制的误差,从而形成比功能性聚合酶更快地复制的较短寄生虫。在通过RNA聚合酶蛋白复制QβRNA的众所周知的实验中,病毒RNA被非常短的非官能序列迅速替换。如果聚合酶是核酶的相同的事情,这意味着终止误差可能会破坏RNA世界。在本文中,我们表明这里研究了RNA复制模型中的情况并非如此。当通过终止误差继续产生所有长度的寄生虫时,由于行波图案的形成,系统可以将其存活到有限的误差阈值;因此,终止错误很重要,但它们不会导致RNA世界的不可避免的寄生虫破坏。最简单的假设是寄生虫复制率与股线长度成反比。在这种最坏的情况下,终止错误的错误阈值远低于点突变。我们还考虑了一种更现实的模型,其中股线的复制时间是聚合酶结合的时间的总和,以及聚合的时间。当考虑绑定步骤时,终止误差比最坏情况更严重。在绑定时间优势的极限中,对所有长度的复制率相等,并且终止的误差阈值与点突变相同。 (c)2017 Elsevier Ltd.保留所有权利。

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