Data from: Magnitude and sign epistasis among deleterious mutations in a positive-sense plant RNA virus

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.

突变间的上位性互作如何决定适合度的遗传架构，是进化研究的核心议题。对上位性的研究在RNA病毒中尤为值得关注，这缘于这类病毒基因组紧凑、缺乏遗传冗余且复杂度相对较低。此外，病毒基因组内的突变互作还决定了抗病毒药物抗性、毒力与宿主范围等关键性状。本研究构建了53个携带成对单核苷酸替换的烟草蚀刻马铃薯Y病毒（Tobacco etch potyvirus）基因型，并测定了它们单独存在与联合存在时的有害适合度效应。结果显示，多达38%的突变对存在显著的适合度上位性，涵盖了偏离乘性效应零假设的正向与负向偏差。值得注意的是，上位性的符号与模型网络中的病毒蛋白-蛋白互作存在显著相关性：存在关联的蛋白对之间的上位性多为正向，而无关联的蛋白对之间则多为负向。进一步分析表明，55%的显著互作属于反符号上位性（reciprocal sign epistasis, RSE），这提示RNA病毒的适应度景观可能具有高度崎岖性。最后，本研究发现上位性的强度与突变的平均效应呈负相关。总体而言，本研究结果与此前针对其他病毒的报道吻合度较高，并进一步巩固了这一观点：对于缺乏遗传鲁棒性的小型紧凑基因组而言，正向上位性是普遍存在的模式。