The origin and underlying driving forces of the SARS-CoV-2 outbreak
The origin and underlying driving forces of the SARS-CoV-2 outbreak
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DOI：
10.1186/s12929-020-00665-8
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发表时间：
2020-06-07
影响因子：
11
通讯作者：
Wang, Hurng-Yi
中科院分区：
文献类型：
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作者：
Chaw, Shu-Miaw;Tai, Jui-Hung;Wang, Hurng-Yi
SARS-CoV-2于2019年12月开始传播，此后成为影响人类社会多个方面的大流行病。关于起源，引入人类的时间，进化模式和驱动SARS-CoV-2爆发的潜在力量的几个问题仍然不清楚。方法分析了截至2020年2月23日137个SARS-CoV-2基因组和相关冠状病毒的遗传变异。结果经突变偏倚校正后，发现该病毒在同义和非同义位点均存在过量的低频突变，这与该病毒最近的暴发流行相一致。与先前报道的SARS-CoV在2003年短暂流行期间的适应性进化相反，我们对SARS-CoV-2基因组的分析显示出放松的迹象。SARS-CoV-2和穿山甲序列之间刺突受体结合域的序列相似性可能是由于大约40年前发生的古老基因组间渐渗。目前的SARS-CoV-2疫情估计起源于2019年11月12日（95% HPD 11/13/2019-12/23/2019）。病毒的有效种群规模显示，自爆发至武汉封城（2020年1月23日）增加约20倍，其后停止增加，证明社交距离在防止其传播方面的有效性。orf 8蛋白的84 S和orf 3蛋白的251 V突变与人为干预巧合地发生。前者于2020年1月5日首次出现，并于2020年1月23日左右达到平稳状态。后者在2020年1月23日之后频率迅速增加。因此，需要阐明这些突变对感染性的作用。来自中国的SARS-CoV-2的遗传多样性是来自世界其他地区的2倍。网络分析发现，从武汉收集的单倍型是内部的，有更多的突变连接，这两个都与SARS-CoV-2疫情起源于中国的观察一致。结论SARS-CoV-2在被发现之前可能已经在人体内秘密传播多年。需要从早期疫情和医院档案中获得数据，以追踪其演变路径，并确定有效传播所需的关键步骤。
Background SARS-CoV-2 began spreading in December 2019 and has since become a pandemic that has impacted many aspects of human society. Several issues concerning the origin, time of introduction to humans, evolutionary patterns, and underlying force driving the SARS-CoV-2 outbreak remain unclear. Method Genetic variation in 137 SARS-CoV-2 genomes and related coronaviruses as of 2/23/2020 was analyzed. Result After correcting for mutational bias, the excess of low frequency mutations on both synonymous and nonsynonymous sites was revealed which is consistent with the recent outbreak of the virus. In contrast to adaptive evolution previously reported for SARS-CoV during its brief epidemic in 2003, our analysis of SARS-CoV-2 genomes shows signs of relaxation. The sequence similarity in the spike receptor binding domain between SARS-CoV-2 and a sequence from pangolin is probably due to an ancient intergenomic introgression that occurred approximately 40 years ago. The current outbreak of SARS-CoV-2 was estimated to have originated on 12/11/2019 (95% HPD 11/13/2019-12/23/2019). The effective population size of the virus showed an approximately 20-fold increase from the onset of the outbreak to the lockdown of Wuhan (1/23/2020) and ceased to increase afterwards, demonstrating the effectiveness of social distancing in preventing its spread. Two mutations, 84S in orf8 protein and 251 V in orf3 protein, occurred coincidentally with human intervention. The former first appeared on 1/5/2020 and plateaued around 1/23/2020. The latter rapidly increased in frequency after 1/23/2020. Thus, the roles of these mutations on infectivity need to be elucidated. Genetic diversity of SARS-CoV-2 collected from China is two times higher than those derived from the rest of the world. A network analysis found that haplotypes collected from Wuhan were interior and had more mutational connections, both of which are consistent with the observation that the SARS-CoV-2 outbreak originated in China. Conclusion SARS-CoV-2 might have cryptically circulated within humans for years before being discovered. Data from the early outbreak and hospital archives are needed to trace its evolutionary path and determine the critical steps required for effective spreading.