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. 2020 Feb 29;40(2):152-158.
doi: 10.12122/j.issn.1673-4254.2020.02.02.

[Analysis of variation and evolution of SARS-CoV-2 genome]

[Article in Chinese]
Yezhen Zhou  1 , Shihao Zhang  1 , Jiayi Chen  1 , Chengsong Wan  1 , Wei Zhao  1 , Bao Zhang  1
Affiliations

[Analysis of variation and evolution of SARS-CoV-2 genome]

[Article in Chinese]
Yezhen Zhou et al. Nan Fang Yi Ke Da Xue Xue Bao. .

Abstract
in English, Chinese

Objective: To analyze the evolution and variation of SARS-CoV-2 during the epidemic starting at the end of 2019.

Methods: We downloaded the full-length genome sequence of SARS-CoV-2 from the databases of GISAID and NCBI. Using the software for bioinformatics including MEGA-X, BEAST, and TempEst, we constructed the genomic evolution tree, inferred the time evolution signal of the virus, calculated the tMRCA time of the virus and analyzed the selection pressure of the virus during evolution.

Results: The phylogenetic tree showed that SARS-CoV-2 belonged to the Sarbecovirus subgenus of β Coronavirus genus together with bat coronavirus BetaCoV/bat/Yunnan/RaTG13/2013, bat-SL-CoVZC45, bat-SL-CoVZXC21 and SARS-CoV. The genomic sequences of SARS-CoV-2 isolated from the ongoing epidemic showed a weak time evolution signal with an average tMRCA time of 73 days (95% CI: 38.9-119.3 days). No positive time evolution signal was found between SARS-CoV-2 and BetaCoV/bat/Yunnan/RaTG13/2013, but the former virus had a strong positive temporal evolution relationship with bat-SL-CoVZC45 and SARS-CoV. The major cause for mutations of SARS-CoV-2 was the pressure of purification selection during the epidemic.

Conclusions: SARS-CoV-2 may have emerged as early as November, 2019, originating most likely from bat-associated coronavirus. This finding may provide evidence for tracing the sources and evolution of the virus.

目的: 分析新型冠状病毒SARS-CoV-2的进化、变异情况。

方法: 从GISAID、NCBI中下载相关病毒全基因组序列，运用生物信息学软件MEGA-X、BEAST、TempEst等软件，构建基因组进化树，推测病毒的时间进化信号，计算病毒出现的tMRCA时间，分析病毒进化的选择压力。

结果: 基因组进化树显示SARS-CoV-2与蝙蝠冠状病毒Beta CoV/bat/Yunnan/RaTG13/2013、bat-SL-CoVZC45、bat-SL-CoVZXC21和SARS-CoV等病毒共同构成冠状病毒β属的Sarbecovirus亚属。现在的病毒序列有微弱的时间进化信号，tMRCA平均时间为73 d，95%可信区间(38.9~119.3 d)，与BetaCoV/bat/Yunnan/RaTG13/2013病毒不具正性时间进化信号，与bat-SL-CoVZC45和SARS-CoV具有强的正性时间进化关系。病毒在流行期间存在变异，主要是净化选择压力。

结论: 病毒SARS-CoV-2可能出现在2019年11月左右，来源于蝙蝠相关冠状病毒。结果将有助于研究病毒SARS-CoV-2的溯源、进化，对疾病进行正确防控具有指导意义。

Keywords: SARS-CoV-2; coronavirus; evolution; mutation.

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Figures

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1
SARS-CoV-2的全基因组进化分析 Phylogenetic analysis of the full-length genome of SRAS-CoV-2. A: Whole genome evolutionary tree of SARS-CoV-2 virus strains(compressed in triangle); B: Unfolded evolutionary tree of 38 isolates of SARS-CoV-2 virus.
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SARS-CoV-2病毒的tMRCA计算 tMRCA of SARS-CoV-2. A: Calculation of evolutionary time signals of SARS-CoV-2 virus. The point indicates the genetic distance of each isolate of the virus from the reference strain (outgroup, tree root) on the time scale; B: Analysis of tMRCA of SARSCoV-2 virus using BEAST.
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SARS-CoV-2病毒与其他冠状病毒进化时间信号检测 Temporal signal test of molecular phylogenies of SARS-CoV-2 together with other coronaviruses. A, B, and C: Evolution time signal detection results of SARS-CoV-2 virus strain and RaTG13, CoVZC45, and SARS-CoV viruses, respectively.
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38株病毒序列变异 Variation of 38 SARS-CoV-2 strains. Each green vertical line represents the the location of variation in the genome, using the earliest BetaCoV/Wuhan/IPBCAMS-WH-01/2019|EPI_ISL_402123 20191224 as the reference sequence.
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