Instituto de Biología Molecular y Celular de Plantas, Consejo Superior de Investigaciones Científicas-UPV, València, Spain.
Heredity (Edinb). 2012 Aug;109(2):71-7. doi: 10.1038/hdy.2012.15. Epub 2012 Apr 11.
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.
突变之间的上位性相互作用如何决定适合度的遗传结构是进化中的核心问题。由于 RNA 病毒基因组的紧凑性、缺乏遗传冗余性和明显的低复杂性，对上位性的研究尤其有趣。此外，病毒基因组中突变之间的相互作用决定了对抗病毒药物的抗性、毒力和宿主范围等特征。在这项研究中，我们生成了 53 种携带一对单核苷酸取代的烟草蚀纹病毒基因型，并测量了它们单独和组合的有害适合度效应。我们发现，高达 38%的配对存在显著的上位性适合度效应，包括与乘法效应的零假设的正偏离和负偏离。有趣的是，上位性的符号与模型网络中的病毒蛋白-蛋白相互作用相关，在连接的蛋白对之间主要是正的，而在不连接的蛋白对之间则是负的。此外，55%的显著相互作用是相互符号上位性（RSE）的情况，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，我们的结果与以前报道的其他病毒的结果非常一致，进一步证实了这样一种观点，即对于缺乏遗传稳健性的小型和紧凑基因组来说，正上位性是常态。
