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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不精确的重组病毒通过聚合酶模板切换事件的适应度驱动的迭代过程进化

DOI:
10.1101/2021.06.01.446546
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发表时间:
2021
期刊:
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通讯作者:
Bentley K
Bentley K
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作者:
Bentley K

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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。利用体外检测,我们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。
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. Utilisingin vitroassays, 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.
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