Imprecise recombinant viruses evolve via a fitness-driven, iterative process of polymerase template-switching events.
Imprecise recombinant viruses evolve via a fitness-driven, iterative process of polymerase template-switching events.
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DOI：
10.1371/journal.ppat.1009676
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发表时间：
2021-08
期刊：
影响因子：
6.7
通讯作者：
Evans DJ
中科院分区：
文献类型：
--
作者：
Bentley K;Alnaji FG;Woodford L;Jones S;Woodman A;Evans DJ
重组是许多正链RNA病毒的共同特征，在病毒进化中起着重要作用。然而，到目前为止，人们对这一过程背后的机制了解有限。利用体外实验，我们之前已经证明重组的模板转换事件是一个随机和普遍的过程，经常导致含有序列重复的不精确基因组的重组病毒。随后，一个被称为分解的过程（尚未进行机制研究）去除这些重复序列，从而产生野生型长度基因组的病毒种群。利用确定的不精确重组病毒，结合Oxford Nanopore和Illumina高通量下一代测序技术，我们研究了分辨率的过程。我们表明，基因组分辨率涉及随后的几轮模板转换重组与病毒适应性，导致一小部分重组基因组存活。这改变了我们以前认为重组和分解是过程中独立步骤的理解，而是表明病毒在很长一段时间内经历频繁和持续的重组事件，直到最适合的病毒，主要是那些具有野生型长度基因组的病毒，在种群中占主导地位。具有正义RNA基因组的病毒，如脊髓灰质炎病毒，有几种进化机制。其中之一是涉及大规模遗传信息交换的重组过程。重组发生在复制过程中，当病毒聚合酶与新生RNA链结合时，从复制一个基因组切换到另一个基因组。然而，聚合酶并不总是准确地在两者之间切换，导致序列重复或缺失，并且基因组被称为不精确。经过多轮复制，序列重复丢失，基因组被分解为野生型长度，但尚不清楚这是如何发生的。在这里，我们使用含有定义序列重复的合成脊髓灰质炎病毒来确定基因组群体经历了反复的重组，直到序列重复丢失，并选择具有精确的野生型长度基因组的病毒。这种选择是基于病毒种群的整体适应度，适应度较低的不精确病毒进化得更快。我们的研究表明，重组是一个持续的过程，其中病毒适应性驱动了一小部分重组变体的选择。这些数据对于了解新型病毒如何通过重组进化以及如何阻断这一过程以防止新型和危险病原体的产生具有重要意义。
Recombination is a common feature of many positive-strand RNA viruses, playing an important role in virus evolution. However, to date, there is limited understanding of the mechanisms behind the process. Utilising in vitro assays, we have previously shown that the template-switching event of recombination is a random and ubiquitous process that often leads to recombinant viruses with imprecise genomes containing sequence duplications. Subsequently, a process termed resolution, that has yet to be mechanistically studied, removes these duplicated sequences resulting in a virus population of wild type length genomes. Using defined imprecise recombinant viruses together with Oxford Nanopore and Illumina high throughput next generation sequencing technologies we have investigated the process of resolution. We show that genome resolution involves subsequent rounds of template-switching recombination with viral fitness resulting in the survival of a small subset of recombinant genomes. This alters our previously held understanding that recombination and resolution are independent steps of the process, and instead demonstrates that viruses undergo frequent and continuous recombination events over a prolonged period until the fittest viruses, predominantly those with wild type length genomes, dominate the population. Viruses with positive-sense RNA genomes, such as poliovirus, have several mechanisms by which they evolve. One of these is the process of recombination involving the large-scale exchange of genetic information. Recombination occurs during replication when the viral polymerase, bound to the nascent RNA chain, switches from copying one genome to another. However, the polymerase does not always accurately switch between the two, resulting in sequence duplications or deletions, and genomes that are referred to as imprecise. Over multiple rounds of replication sequence duplications are lost and genomes are resolved to wild type length, but it is unclear how this occurs. Here we used synthetic polioviruses containing defined sequence duplications to determine that the genome population undergoes repeated rounds of recombination until sequence duplications are lost and viruses with precise, wild type length genomes are selected for. This selection is based on the overall fitness of the virus population, with less fit imprecise viruses evolving more quickly. Our study suggests that recombination is a continual process where virus fitness drives the selection of a small subset of recombinant variants. These data are important for understanding how novel viruses evolve via recombination and how this process can be blocked to prevent novel and dangerous pathogens from arising.
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影响因子：
64.8
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