SUMMARY Reproduction of RNA viruses is typically error-prone due to the infidelity of their replicative machinery and the usual lack of proofreading mechanisms. The error rates may be close to those that kill the virus. Consequently, populations of RNA viruses are represented by heterogeneous sets of genomes with various levels of fitness. This is especially consequential when viruses encounter various bottlenecks and new infections are initiated by a single or few deviating genomes. Nevertheless, RNA viruses are able to maintain their identity by conservation of major functional elements. This conservatism stems from genetic robustness or mutational tolerance, which is largely due to the functional degeneracy of many protein and RNA elements as well as to negative selection. Another relevant mechanism is the capacity to restore fitness after genetic damages, also based on replicative infidelity. Conversely, error-prone replication is a major tool that ensures viral evolvability. The potential for changes in debilitated genomes is much higher in small populations, because in the absence of stronger competitors low-fit genomes have a choice of various trajectories to wander along fitness landscapes. Thus, low-fit populations are inherently unstable, and it may be said that to run ahead it is useful to stumble. In this report, focusing on picornaviruses and also considering data from other RNA viruses, we review the biological relevance and mechanisms of various alterations of viral RNA genomes as well as pathways and mechanisms of rehabilitation after loss of fitness. The relationships among mutational robustness, resilience, and evolvability of viral RNA genomes are discussed.

摘要RNA 病毒的复制通常容易出错，因为它们的复制机制不可靠且通常缺乏校对机制。错误率可能接近杀死病毒的错误率。因此，RNA 病毒群体由具有不同适应性水平的异质基因组代表。当病毒遇到各种瓶颈并且由单个或几个偏差基因组引发新的感染时，这一点尤其重要。然而，RNA 病毒能够通过保护主要功能元件来保持其身份。这种保守性源于遗传稳健性或突变耐受性，这在很大程度上是由于许多蛋白质和RNA元件的功能简并以及负选择造成的。另一个相关机制是基因损伤后恢复健康的能力，也是基于复制不忠。相反，容易出错的复制是确保病毒进化性的主要工具。在小群体中，衰弱的基因组发生变化的可能性要高得多，因为在没有更强大的竞争对手的情况下，低适应性基因组可以选择各种轨迹来沿着适应性景观徘徊。因此，低适应群体本质上是不稳定的，可以说，要跑得快，跌倒才有用。在这份报告中，我们重点关注小核糖核酸病毒，并考虑其他RNA病毒的数据，回顾了病毒RNA基因组各种改变的生物学相关性和机制，以及失能后康复的途径和机制。讨论了病毒 RNA 基因组的突变稳健性、弹性和进化性之间的关系。