Decoding the evolution and transmissions of the novel pneumonia coronavirus (SARS-CoV-2 / HCoV-19) using whole genomic data
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摘要:
2019年12月中旬新型肺炎疫情(COVID-19)在湖北武汉爆发，截至2020年2月29日，新冠病毒SARS-CoV-2（2019-nCoV/HCoV-19）已感染全球85 000多人。在本研究中，我们使用了GISAID EpiFluTM数据库中的93个完整新冠病毒基因组来解析新冠病毒在疫情爆发前两个月的演化，以及人际传播情况。我们采用系统发育网状分析方法，构建了SARS-CoV-2基因组的单倍型的演化关系，并进一步对病毒的潜在种群大小变化进行估算。利用公式t =τ/ 2u，基于扩展参数tau（τ）推算了病毒可能发生扩张（即大量人传人）日期。在新冠病毒基因组的八个编码区中共发现120个的变异位点，关联119个密码子有79个非同义和40个同义替换。我们猜测40个改变氨基酸属性的非同义替换可能与病毒适应性有关。另外，我们分析中没有检测到病毒重组事件。从93个病毒基因组中鉴定出58种单倍型，将其划分为五组用于传播和扩散分析。通过蝙蝠冠状病毒基因组（bat-RaTG13-CoV）作为外群，我们发现单倍型H13和H38可能是古老的单倍型，单倍型H1是从单倍型H3演化而来。种群扩张时间估算发现在2020年1月6日和2019年12月8日可能发生大量人传人。此外，我们利用谱系流行病学方法回溯了一些人际传播事件。同时，这种方法可以用于寻找感染病例的病毒感染源。
Abstract:The outbreak of COVID-19 started in mid-December 2019 in Wuhan, China. Up to 29 February 2020, SARS-CoV-2 (HCoV-19 / 2019-nCoV) had infected more than 85 000 people in the world. In this study, we used 93 complete genomes of SARS-CoV-2 from the GISAID EpiFluTM database to investigate the evolution and human-to-human transmissions of SARS-CoV-2 in the first two months of the outbreak. We constructed haplotypes of the SARS-CoV-2 genomes, performed phylogenomic analyses and estimated the potential population size changes of the virus. The date of population expansion was calculated based on the expansion parameter tau (τ) using the formula t=τ/2u. A total of 120 substitution sites with 119 codons, including 79 non-synonymous and 40 synonymous substitutions, were found in eight coding-regions in the SARS-CoV-2 genomes. Forty non-synonymous substitutions are potentially associated with virus adaptation. No combinations were detected. The 58 haplotypes (31 found in samples from China and 31 from outside China) were identified in 93 viral genomes under study and could be classified into five groups. By applying the reported bat coronavirus genome (bat-RaTG13-CoV) as the outgroup, we found that haplotypes H13 and H38 might be considered as ancestral haplotypes, and later H1 was derived from the intermediate haplotype H3. The population size of the SARS-CoV-2 was estimated to have undergone a recent expansion on 06 January 2020, and an early expansion on 08 December 2019. Furthermore, phyloepidemiologic approaches have recovered specific directions of human-to-human transmissions and the potential sources for international infected cases.
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Key words:
- COVID-19 /
- HCoV-19 /
- SARS-CoV-2 /
- Novel pneumonia outbreak /
- Human-to-human transmission /
- Phyloepidemiology
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Figure 1. Summary information for 120 substitution sites crossing eight coding sequence regions in the aligned SARS-CoV-2 genomic sequences
Figure 2. Genomic haplotypes of SARS-CoV-2 changes between the collection dates of samples
The confirmed samples from the Huanan Seafood Wholesale Market are indicated using red circles, and a confirmed sample with no link to the market is indicated using a blue circle.
Figure 3. Evolutionary relationship and geographical distribution of 58 haplotypes of SARS-CoV-2 (A, B)
Proposed evolutionary paths (C) of haplotypes and possible transmission and spreading routes (D) are also inferred based on evolutionary analyses and epidemiologic research. Sample sizes of haplotypes and regions are annotated in the circles.
Figure 4. Phylogenetic networks of 58 haplotypes of SARS-CoV-2 with the outgroup bat-RaTG13-CoV using the whole coding region matrix (A) and 120 substitution sites (B), referring to all variable sites of coding regions in SARS-CoV-2 haplotypes
The bottom scale bars represent the number of substitutions per site. The open box on branches of bat-RaTG13-CoV (A), H15 (A, B), and H17 (A, B) indicating a long branch was clipped.
Figure 5. The inferred relationships between the outgroup bat-RaTG13-CoV and four associated/central node haplotypes (H1, H3, H13, and H38) of SARS-CoV-2 using three datasets
The dataset of four core substitution sites is the four variable sites shared among bat-RaTG13-CoV and the four central node haplotypes. The dataset of 120 substitution sites refers to all variable sites of coding regions in SARS-CoV-2 haplotypes. The dataset of 1235 substitution sites refers to all variable sites of coding regions among bat-RaTG13-CoV and SARS-CoV-2 haplotypes.
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