Institute of Infection, Veterinary and Ecological Sciences, Faculty of Health and Life Sciences, University of Liverpool, Liverpool L3 5RF, UK.
Health Protection Research Unit in Emerging and Zoonotic Infections, Liverpool L69 7BE, UK.
Viruses. 2023 Aug 12;15(8):1728. doi: 10.3390/v15081728.
SARS-CoV-2 began spreading through human-to-human transmission first within China and then worldwide, with increasing sequence diversity associated with time and the further spread of the virus. The spillover events in the Huanan market were associated with two lineages of SARS-CoV-2 (lineages A and B). Infecting virus populations and those in infected individuals consist of a dominant genomic sequence and minor genomic variants; these latter populations can indicate sites on the genome that may be subject to mutational changes-either neutral or advantageous sites and those that act as a reservoir for future dominant variants-when placed under selection pressure. The earliest deposited sequences with human infections associated with the Huanan market shared very close homology with each other and were all lineage B. However, there were minor genomic variants present in each sample that encompassed synonymous and non-synonymous changes. Fusion sequences characteristic of defective RNA were identified that could potentially link transmission chains between individuals. Although all the individuals appeared to have lineage B as the dominant sequence, nucleotides associated with lineage A could be found at very low frequencies. Several substitutions (but not deletions) associated with much later variants of concern (VoCs) were already present as minor genomic variants. This suggests that low-frequency substitutions at the start of a pandemic could be a reservoir of future dominant variants and/or provide information on potential sites within the genome associated with future plasticity.
SARS-CoV-2 首先在中国境内并随后在全球范围内开始通过人际传播，随着时间的推移和病毒的进一步传播，序列多样性不断增加。华南市场的溢出事件与两种 SARS-CoV-2 谱系（谱系 A 和 B）有关。感染病毒种群和受感染个体中的病毒种群由主要基因组序列和次要基因组变异体组成；这些后一组群可以指示基因组中可能发生突变的位点——无论是中性或有利的位点，还是作为未来优势变异体的储备库，当受到选择压力时。与华南市场相关的最早与人感染相关的已存档序列彼此之间具有非常密切的同源性，均为谱系 B。然而，每个样本中都存在较小的基因组变异体，包括同义突变和非同义突变。鉴定出具有特征性缺陷 RNA 的融合序列，这可能在个体之间的传播链之间建立联系。尽管所有个体似乎都以谱系 B 作为主要序列，但在非常低的频率下可以发现与谱系 A 相关的核苷酸。一些与后来的关注变体（VoC）相关的替换（但不是缺失）已经作为次要基因组变异体存在。这表明大流行开始时低频替换可能是未来优势变体的储备库，或提供与未来可塑性相关的基因组内潜在位点的信息。
