Three highly pathogenic human coronaviruses can cause severe acute respiratory syndrome (SARS-CoV, SARS-CoV-2 and MERS-CoV). Although phylogenetic analyses have indicated ancient origin of human coronaviruses from animal relatives, their evolutionary history remains to be established. Using phylogenetics and “high order genomic structures” including trimer spectrums, codon usage and dinucleotide suppression, we observed distinct clustering of all human coronaviruses that formed phylogenetic clades with their closest animal relatives, indicating they have encompassed long evolutionary histories within specific ecological niches before jumping species barrier to infect humans. The close relationships between SARS-CoV and SARS-CoV-2 imply similar evolutionary origin. However, a lower Effective Codon Number (ENC) pattern and CpG dinucleotide suppression in SARS-CoV-2 genomes compared to SARS-CoV and MERS-CoV may imply a better host fitness, and thus their success in sustaining a pandemic. Characterization of coronavirus heterogeneity via complementary approaches enriches our understanding on the evolution and virus-host interaction of these emerging human pathogens while the underlying mechanistic basis in pathogenicity warrants further investigation.

三种高致病性人类冠状病毒可引起严重急性呼吸系统综合症（SARS-CoV、SARS-CoV-2 和 MERS-CoV）。尽管系统发育分析表明人类冠状病毒起源于动物亲属，但它们的进化史仍有待确定。使用系统发育学和“高阶基因组结构”（包括三聚体谱、密码子使用和二核苷酸抑制），我们观察到所有人类冠状病毒的明显聚类，这些冠状病毒与其最近的动物亲缘形成系统发育进化枝，表明它们在跳跃之前在特定生态位内包含了长期的进化历史感染人类的​​物种屏障。SARS-CoV 和 SARS-CoV-2 之间的密切关系意味着相似的进化起源。然而，与 SARS-CoV 和 MERS-CoV 相比，SARS-CoV-2 基因组中较低的有效密码子数 (ENC) 模式和 CpG 二核苷酸抑制可能意味着宿主适应性更好，因此它们成功维持了大流行。通过互补方法表征冠状病毒异质性丰富了我们对这些新兴人类病原体的进化和病毒-宿主相互作用的理解，而致病性的潜在机制基础值得进一步研究。