Viruses accumulate mutations under the influence of natural selection and host–virus interactions. Through a systematic comparison of 351,525 full viral genome sequences collected during the recent COVID-19 pandemic, we reveal the spectrum of SARS-CoV-2 mutations. Unlike those of other viruses, the mutational spectrum of SARS-CoV-2 exhibits extreme asymmetry, with a much higher rate of C>U than U>C substitutions, as well as a higher rate of G>U than U>G substitutions. This suggests directional genome sequence evolution during transmission. The substantial asymmetry and directionality of the mutational spectrum enable pseudotemporal tracing of SARS-CoV-2 without prior information about the root sequence, collection time, and sampling region. This shows that the viral genome sequences collected in Asia are similar to the original genome sequence. Adjusted estimation of the dN/dS ratio accounting for the asymmetrical mutational spectrum also shows evidence of negative selection on viral genes, consistent with previous reports. Our findings provide deep insights into the mutational processes in SARS-CoV-2 viral infection and advance the understanding of the history and future evolution of the virus.

病毒在自然选择和宿主-病毒相互作用的影响下积累突变。通过对最近 COVID-19 大流行期间收集的 351,525 个完整病毒基因组序列的系统比较，我们揭示了 SARS-CoV-2 突变的范围。与其他病毒不同，SARS-CoV-2 的突变谱表现出极端的不对称性，C>U 的取代率远高于 U>C 的取代率，G>U 的取代率也高于 U>G 的取代率。这表明传输过程中的定向基因组序列进化。突变谱的显着不对称性和方向性能够在没有关于根序列、收集时间和采样区域的先验信息的情况下对 SARS-CoV-2 进行伪时间追踪。这说明在亚洲采集的病毒基因组序列与原始基因组序列相似。d 的调整估计不对称突变谱的N / d S比率也显示了病毒基因负选择的证据，与之前的报告一致。我们的发现为 SARS-CoV-2 病毒感染的突变过程提供了深入的见解，并促进了对该病毒的历史和未来进化的理解。