Natural selection operating on the genomes of viral pathogens in different host species strongly contributes to adaptation facilitating host colonization. Here, we analyse, quantify and compare viral adaptation in genomic sequence data derived from seven zoonotic events in the Coronaviridae family among primary, intermediate and human hosts. Rates of nonsynonymous (dN ) and synonymous (dS ) changes on specific amino acid positions were quantified for each open reading frame (ORF). Purifying selection accounted for 77% of all sites under selection. Diversifying selection was most frequently observed in viruses infecting the primary hosts of each virus and predominantly occurred in the orf1ab genomic region. Within all four intermediate hosts, diversifying selection on the spike gene was observed either solitarily or in combination with orf1ab and other genes. Consistent with previous evidence, pervasive diversifying selection on coronavirus spike genes corroborates the role this protein plays in host cellular entry, adaptation to new hosts and evasion of host cellular immune responses. Structural modelling of spike proteins identified a significantly higher proportion of sites for SARS-CoV-2 under positive selection in close proximity to sites of glycosylation relative to the other coronaviruses. Among human coronaviruses, there was a significant inverse correlation between the number of sites under positive selection and the estimated years since the virus was introduced into the human population. Abundant diversifying selection observed in SARS-CoV-2 suggests the virus remains in the adaptive phase of the host switch, typical of recent host switches. A mechanistic understanding of where, when and how genomic adaptation occurs in coronaviruses following a host shift is crucial for vaccine design, public health responses and predicting future pandemics.

中文翻译：

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冠状病毒之间基因组和宿主适应的可变途径。

对不同宿主物种中病毒病原体基因组的自然选择对促进宿主定植的适应有很大贡献。在这里，我们分析、量化和比较来自冠状病毒科的七个人畜共患病事件的基因组序列数据中的病毒适应性，这些数据来源于初级、中间和人类宿主中的冠状病毒科动物。对每个开放阅读框 (ORF) 量化特定氨基酸位置的非同义 (dN) 和同义 (dS) 变化率。净化选择占所有被选择站点的77%。在感染每种病毒的主要宿主的病毒中最常观察到多样化选择，并且主要发生在 orf1ab 基因组区域。在所有四个中间宿主中，单独或与 orf1ab 和其他基因组合观察到对刺突基因的多样化选择。与先前的证据一致，对冠状病毒刺突基因的普遍多样化选择证实了这种蛋白质在宿主细胞进入、适应新宿主和逃避宿主细胞免疫反应中的作用。刺突蛋白的结构模型发现，与其他冠状病毒相比，在靠近糖基化位点的正选择下，SARS-CoV-2 位点的比例要高得多。在人类冠状病毒中，阳性选择的位点数量与自病毒引入人群以来的估计年数之间存在显着的负相关。在 SARS-CoV-2 中观察到的大量多样化选择表明该病毒仍处于宿主转换的适应阶段，这是最近宿主转换的典型特征。对宿主转变后冠状病毒基因组适应发生的地点、时间和方式的机制理解对于疫苗设计、公共卫生反应和预测未来的大流行至关重要。