Evolution of Mutational Robustness in an RNA Virus

Mutational (genetic) robustness is phenotypic constancy in the face of mutational changes to the genome. Robustness is critical to the understanding of evolution because phenotypically expressed genetic variation is the fuel of natural selection. Nonetheless, the evidence for adaptive evolution of mutational robustness in biological populations is controversial. Robustness should be selectively favored when mutation rates are high, a common feature of RNA viruses. However, selection for robustness may be relaxed under virus co-infection because complementation between virus genotypes can buffer mutational effects. We therefore hypothesized that selection for genetic robustness in viruses will be weakened with increasing frequency of co-infection. To test this idea, we used populations of RNA phage ϕ6 that were experimentally evolved at low and high levels of co-infection and subjected lineages of these viruses to mutation accumulation through population bottlenecking. The data demonstrate that viruses evolved under high co-infection show relatively greater mean magnitude and variance in the fitness changes generated by addition of random mutations, confirming our hypothesis that they experience weakened selection for robustness. Our study further suggests that co-infection of host cells may be advantageous to RNA viruses only in the short term. In addition, we observed higher mutation frequencies in the more robust viruses, indicating that evolution of robustness might foster less-accurate genome replication in RNA viruses.

突变稳健性（mutational robustness，亦称遗传稳健性）是指基因组发生突变改变时，表型仍维持恒定的特性。稳健性是演化研究的关键议题，因为表型显现的遗传变异是自然选择的核心原料。然而，生物种群中突变稳健性的适应性演化相关证据仍存在争议。在突变率较高的场景下，稳健性会受到自然选择的青睐，而高突变率正是RNA病毒的典型特征。但在病毒共感染的情况下，对稳健性的选择压力可能会被缓解：不同病毒基因型间的互补作用能够缓冲突变带来的有害影响。据此我们提出假说：病毒对遗传稳健性的选择强度会随共感染频率的升高而减弱。为验证该假说，我们以RNA噬菌体ϕ6为研究对象，通过实验设置低、高两种共感染水平进行演化培养，并通过种群瓶颈操作使这些病毒的谱系发生突变积累。实验数据显示，在高共感染条件下演化得到的病毒，其随机突变引发的适合度变化的平均幅度与变异程度均相对更高，这证实了我们的假说：这类病毒所承受的稳健性选择压力确实有所减弱。本研究还表明，宿主细胞的共感染或许仅在短期内对RNA病毒具有演化优势。此外，我们发现稳健性更强的病毒其突变频率更高，这提示RNA病毒的稳健性演化可能会降低基因组复制的准确性。