Data from: Cell tropism predicts long-term nucleotide substitution rates of mammalian RNA viruses

The high rates of RNA virus evolution are generally attributed to replication with error-prone RNA-dependent RNA polymerases. However, these long-term nucleotide substitution rates span three orders of magnitude and do not correlate well with mutation rates or selection pressures. This substitution rate variation may be explained by differences in virus ecology or intrinsic genomic properties. We generated nucleotide substitution rate estimates for mammalian RNA viruses and compiled comparable published rates, yielding a dataset of 118 substitution rates of structural genes from 51 different species, as well as 40 rates of non-structural genes from 28 species. Through ANCOVA analyses, we evaluated the relationships between these rates and four ecological factors: target cell, transmission route, host range, infection duration; and three genomic properties: genome length, genome sense, genome segmentation. Of these seven factors, we found target cells to be the only significant predictors of viral substitution rates, with tropisms for epithelial cells or neurons (P<0.0001) as the most significant predictors. Further, one-tailed t-tests showed that viruses primarily infecting epithelial cells evolve significantly faster than neurotropic viruses (P<0.0001 and P<0.001 for the structural genes and non-structural genes, respectively). These results provide strong evidence that the fastest evolving mammalian RNA viruses infect cells with the highest turnover rates: the highly proliferative epithelial cells. Estimated viral generation times suggest that epithelial-infecting viruses replicate more quickly than viruses with different cell tropisms. Our results indicate that cell tropism is a key factor in viral evolvability.RNA病毒的高进化速率通常被归因于其借助易错RNA依赖RNA聚合酶（RNA-dependent RNA polymerase）完成的复制过程。然而，这类病毒的长期核苷酸替换速率跨度可达三个数量级，且与突变率或选择压力的相关性并不显著。这种替换速率的差异或可通过病毒的生态学特性与内在基因组属性的差异加以解释。我们针对哺乳动物RNA病毒开展了核苷酸替换速率估算，并整理了已发表的可比速率数据，最终构建得到一套数据集：包含来自51个不同物种的118个结构基因替换速率，以及来自28个物种的40个非结构基因替换速率。通过协方差分析（ANCOVA），我们评估了上述替换速率与四类生态学因素（靶细胞、传播途径、宿主范围、感染时长）以及三类基因组属性（基因组长度、基因组正义性、基因组分段情况）之间的关联。在这七类因素中，我们发现靶细胞是唯一能够显著预测病毒替换速率的因素，其中以上皮细胞或神经元为细胞嗜性的病毒（P<0.0001）是最具显著性的预测因子。进一步的单尾t检验结果显示，主要感染上皮细胞的病毒进化速率显著快于嗜神经性病毒（结构基因组与非结构基因组的P值分别小于0.0001与0.001）。上述结果提供了强有力的证据：进化最快的哺乳动物RNA病毒所感染的正是细胞更新速率最高的一类细胞——即高度增殖的上皮细胞。基于估算的病毒世代时间可知，感染上皮细胞的病毒的复制速率要快于具有其他细胞嗜性的病毒。我们的研究结果表明，细胞嗜性是决定病毒进化能力的关键因素。