Lázaro Ester, Escarmís Cristina, Pérez-Mercader Juan, Manrubia Susanna C, Domingo Esteban
Centro de Astrobiología (Consejo Superior de Investigaciones Científicas-Instituto Nacional de Técnica Aeroespacial), Associated with the National Aeronautics and Space Administration Astrobiology Institute, Torrejón de Ardoz, Madrid, Spain.
Proc Natl Acad Sci U S A. 2003 Sep 16;100(19):10830-5. doi: 10.1073/pnas.1332668100. Epub 2003 Sep 5.
RNA viruses display high mutation rates and their populations replicate as dynamic and complex mutant distributions, termed viral quasispecies. Repeated genetic bottlenecks, which experimentally are carried out through serial plaque-to-plaque transfers of the virus, lead to fitness decrease (measured here as diminished capacity to produce infectious progeny). Here we report an analysis of fitness evolution of several low fitness foot-and-mouth disease virus clones subjected to 50 plaque-to-plaque transfers. Unexpectedly, fitness decrease, rather than being continuous and monotonic, displayed a fluctuating pattern, which was influenced by both the virus and the state of the host cell as shown by effects of recent cell passage history. The amplitude of the fluctuations increased as fitness decreased, resulting in a remarkable resistance of virus to extinction. Whereas the frequency distribution of fitness in control (independent) experiments follows a log-normal distribution, the probability of fitness values in the evolving bottlenecked populations fitted a Weibull distribution. We suggest that multiple functions of viral genomic RNA and its encoded proteins, subjected to high mutational pressure, interact with cellular components to produce this nontrivial, fluctuating pattern.
RNA病毒显示出高突变率，其群体以动态且复杂的突变体分布进行复制，称为病毒准种。重复的基因瓶颈，在实验中通过病毒的连续空斑到空斑转移来实现，会导致适应性下降（在此处衡量为产生感染性子代的能力减弱）。在此，我们报告了对几个低适应性口蹄疫病毒克隆进行50次空斑到空斑转移后的适应性进化分析。出乎意料的是，适应性下降并非连续且单调的，而是呈现出一种波动模式，如近期细胞传代历史的影响所示，这种模式受到病毒和宿主细胞状态的共同影响。随着适应性下降，波动幅度增大，导致病毒具有显著的抗灭绝能力。在对照（独立）实验中，适应性的频率分布遵循对数正态分布，而在经历瓶颈进化的群体中，适应性值的概率符合威布尔分布。我们认为，在高突变压力下，病毒基因组RNA及其编码蛋白的多种功能与细胞成分相互作用，从而产生了这种非平凡的波动模式。
