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arXiv 1410.7836physics.bio-phq-bio.BM
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同义突变降低二十面体ssRNA病毒的基因组紧凑性

Synonymous mutations reduce genome compactness in icosahedral ssRNA viruses

Luca Tubiana, Anže Lošdorfer Božič, Cristian Micheletti, Rudi Podgornik

摘要:

最近的研究表明,单链病毒RNA折叠成比具有相似化学组成和相同长度的随机RNA序列更紧凑的结构。基于这种比较,已经表明野生型病毒RNA可能已经进化为在分子结构上紧密的,以帮助其折叠并协助病毒组装过程。为了进一步探讨紧凑性选择假说,我们系统地比较了预测的大小超过100个野生型病毒序列与它们的突变体,这是在硅片上进化,并受到一些已知的进化限制。特别是,我们强制突变同义性,保留密码子偏好,并保持非翻译区完整。研究发现,这些限制性突变的逐渐积累仍然足以完全消除病毒RNA基因组的特征性紧凑性印记,使它们在这方面与随机改组的RNA在物理上无法区分。这表明保持基因组的物理紧凑性确实是ssRNA病毒进化限制中的主要因素,也有助于证明病毒ssRNA基因组中的同义突变不是严格中性的。

英文摘要:

Recent studies have shown that single-stranded viral RNAs fold into more compact structures than random RNA sequences with similar chemical composition and identical length. Based on this comparison it has been suggested that wild-type viral RNA may have evolved to be atypically compact so as to aid its encapsidation and assist the viral assembly process. In order to further explore the compactness selection hypothesis, we systematically compare the predicted sizes of more than one hundred wild-type viral sequences with those of their mutants, which are evolved in silico and subject to a number of known evolutionary constraints. In particular, we enforce mutation synonynimity, preserve the codon-bias, and leave untranslated regions intact. It is found that progressive accumulation of these restricted mutations still suffices to completely erase the characteristic compactness imprint of the viral RNA genomes, making them in this respect physically indistinguishable from randomly shuffled RNAs. This shows that maintaining the physical compactness of the genome is indeed a primary factor among ssRNA viruses evolutionary constraints, contributing also to the evidence that synonymous mutations in viral ssRNA genomes are not strictly neutral.

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