Shapiro Beth, Rambaut Andrew, Pybus Oliver G, Holmes Edward C
Department of Zoology, Oxford University, Oxford, United Kingdom.
Mol Biol Evol. 2006 Sep;23(9):1724-30. doi: 10.1093/molbev/msl037. Epub 2006 Jun 14.
RNA virus genomes are compact, often containing multiple overlapping reading frames and functional secondary structure. Consequently, it is thought that evolutionary interactions between nucleotide sites are commonplace in the genomes of these infectious agents. However, the role of epistasis in natural populations of RNA viruses remains unclear. To investigate the pervasiveness of epistasis in RNA viruses, we used a parsimony-based computational method to identify pairs of co-occurring mutations along phylogenies of 177 RNA virus genes. This analysis revealed widespread evidence for positive epistatic interactions at both synonymous and nonsynonymous nucleotide sites and in both clonal and recombining viruses, with the majority of these interactions spanning very short sequence regions. These findings have important implications for understanding the key aspects of RNA virus evolution, including the dynamics of adaptation. Additionally, many comparative analyses that utilize the phylogenetic relationships among gene sequences assume that mutations represent independent, uncorrelated events. Our results show that this assumption may often be invalid.
RNA病毒基因组较为紧凑，通常包含多个重叠阅读框和功能性二级结构。因此，人们认为核苷酸位点之间的进化相互作用在这些感染性因子的基因组中很常见。然而，上位性在RNA病毒自然群体中的作用仍不明确。为了研究上位性在RNA病毒中的普遍性，我们使用了一种基于简约法的计算方法，沿着177个RNA病毒基因的系统发育树识别同时出现的突变对。该分析揭示了在同义核苷酸位点和非同义核苷酸位点、以及克隆病毒和重组病毒中，均广泛存在正向上位性相互作用的证据，其中大多数相互作用跨越的序列区域非常短。这些发现对于理解RNA病毒进化的关键方面，包括适应动态，具有重要意义。此外，许多利用基因序列间系统发育关系的比较分析都假定突变代表独立、不相关的事件。我们的结果表明，这一假设可能常常是无效的。
