Magnitude and sign epistasis among deleterious mutations in a positive-sense plant RNA virus
Magnitude and sign epistasis among deleterious mutations in a positive-sense plant RNA virus
复制标题
DOI：
10.1038/hdy.2012.15
复制
发表时间：
2012-08-01
期刊：
影响因子：
3.8
通讯作者：
Elena, S. F.
中科院分区：
文献类型：
--
作者：
Lalic, J.;Elena, S. F.
突变之间的上位相互作用如何决定适应性的遗传结构在进化中是至关重要的。RNA病毒的上位性研究特别有趣，因为它们的基因组紧凑，缺乏遗传冗余，并且明显的低复杂性。此外，病毒基因组突变之间的相互作用决定了诸如抗病毒药物耐药性、毒力和宿主范围等性状。在本研究中，我们获得了53个携带单核苷酸取代对的烟草蚀刻多病毒基因型，并测量了它们分离和组合的有害适合度效应。我们发现，高达38%的配对具有显著的适应性上位性，包括与乘法效应零假设的正偏差和负偏差。有趣的是，上位性的标志与模型网络中的病毒蛋白-蛋白相互作用相关，在连接的蛋白质对之间主要为正，而在未连接的蛋白质对之间主要为负。此外，55%的显著相互作用是互序上位（RSE），表明RNA病毒的适应景观可能非常崎岖。最后，我们发现上位性的大小与突变的平均效应呈负相关。总的来说，我们的结果与之前报道的其他病毒的结果很好地一致，并进一步巩固了阳性上位性是缺乏遗传稳健性的小而紧凑基因组的标准的观点。遗传（2012）109,71-77；doi: 10.1038 / hdy.2012.15;2012年4月11日在线发布
How epistatic interactions between mutations determine the genetic architecture of fitness is of central importance in evolution. The study of epistasis is particularly interesting for RNA viruses because of their genomic compactness, lack of genetic redundancy, and apparent low complexity. Moreover, interactions between mutations in viral genomes determine traits such as resistance to antiviral drugs, virulence and host range. In this study we generated 53 Tobacco etch potyvirus genotypes carrying pairs of single-nucleotide substitutions and measured their separated and combined deleterious fitness effects. We found that up to 38% of pairs had significant epistasis for fitness, including both positive and negative deviations from the null hypothesis of multiplicative effects. Interestingly, the sign of epistasis was correlated with viral protein-protein interactions in a model network, being predominantly positive between linked pairs of proteins and negative between unlinked ones. Furthermore, 55% of significant interactions were cases of reciprocal sign epistasis (RSE), indicating that adaptive landscapes for RNA viruses maybe highly rugged. Finally, we found that the magnitude of epistasis correlated negatively with the average effect of mutations. Overall, our results are in good agreement to those previously reported for other viruses and further consolidate the view that positive epistasis is the norm for small and compact genomes that lack genetic robustness. Heredity (2012) 109, 71-77; doi: 10.1038/hdy.2012.15; published online 11 April 2012