Mutagenesis Scanning Uncovers Evolutionary Constraints on Tobacco Etch Potyvirus Membrane-Associated 6K2 Protein

文献类型： 外文期刊

第一作者： Elena, Santiago F.

作者： Elena, Santiago F.;Wu, Beilei;Martinez, Fernando;Li, Xianghua;Elena, Santiago F.;Wu, Beilei

作者机构：

关键词： bulk selection; mutagenesis; Potyvirus; TEV; virulence; virus fitness

期刊名称：GENOME BIOLOGY AND EVOLUTION （ 影响因子：3.416； 五年影响因子：4.079 ）

ISSN： 1759-6653

年卷期： 2019 年 11 卷 4 期

页码：

收录情况： SCI

摘要： RNA virus high mutation rate is a double-edged sword. At the one side, most mutations jeopardize proteins functions; at the other side, mutations are needed to fuel adaptation. The relevant question then is the ratio between beneficial and deleterious mutations. To evaluate this ratio, we created a mutant library of the 6K2 gene of tobacco etch potyvirus that contains every possible single-nucleotide substitution. 6K2 protein anchors the virus replication complex to the network of endoplasmic reticulum membranes. The library was inoculated into the natural host Nicotiana tabacum, allowing competition among all these mutants and selection of those that are potentially viable. We identified 11 nonsynonymous mutations that remain in the viral population at measurable frequencies and evaluated their fitness. Some had fitness values higher than the wild-type and some were deleterious. The effect of these mutations in the structure, transmembrane properties, and function of 6K2 was evaluated in silico. In parallel, the effect of these mutations in infectivity, virus accumulation, symptoms development, and subcellular localization was evaluated in the natural host. The alpha-helixH1 in the N-terminal part of 6K2 turned out to be under purifying selection, while most observed mutations affect the link between transmembrane alpha-helices H2 and H3, fusing them into a longer helix and increasing its rigidity. In general, these changes are associated with higher within-host fitness and development of milder or no symptoms. This finding suggests that in nature selection upon 6K2 may result from a tradeoff between within-host accumulation and severity of symptoms.

分类号：

  • 相关文献
作者其他论文 更多>>

微信小程序