人类和动物冠状病毒基因组中不断演变的核糖核衣壳组装/包装信号：靶向，传播和进化
Evolving ribonucleocapsid assembly/packaging signals in the genomes of the human and animal coronaviruses: targeting, transmission and evolution
摘要：
COVID-19全球大流行有力地加强了对冠状病毒相关分子机制的研究。只有通过详细的比较研究，才能在更广泛的进化层面上理解冠状病毒的起源以及冠状病毒感染的人传人、动物传人和人畜传播的风险。本论文研究了7种已知的人类冠状病毒SARS-CoV、SARS-CoV-2、MERS-CoV、HCoV-OC 43、HCoV-HKU 1、HCoV-229 E和HCoV-NL 63基因组中的核糖核衣壳组装包装信号（RNAPS），并与相关动物冠状病毒SARS-Bat-CoV、MERS-Camel-CoV、MHV、Bat-CoV MOP 1、TGEV、和一种骆驼冠状病毒。冠状病毒基因组中的RNAPS是由于基因组RNA与螺旋核衣壳中的N蛋白之间的弱特异性相互作用而进化的。结合过渡基因组定位和Jaccard相关系数，使我们能够直接进行分析的基础图案分布在基因组。在所有冠状病毒中，RNAPS在基因组中均呈准周期性分布，其周期约为54 nt，比SARS-CoV长的基因组偏向于57 nt，比SARS-CoV短的基因组偏向于51 nt。与MERS-CoV、MHV和TGEV的实验验证包装信号的比较证明，特定基序的分布与包装信号密切相关。我们还发现，许多基序在整个谱系的基因组上的特征和定位都是高度保守的，这使它们成为有希望的治疗靶点。其作用机制也会影响重组和共感染。
英文摘要：
A world-wide COVID-19 pandemic intensified strongly the studies of molecular mechanisms related to the coronaviruses. The origin of coronaviruses and the risks of human-to-human, animal-to-human, and human-to-animal transmission of coronaviral infections can be understood only on a broader evolutionary level by detailed comparative studies. In this paper, we studied ribonucleocapsid assembly-packaging signals (RNAPS) in the genomes of all seven known pathogenic human coronaviruses, SARS-CoV, SARS-CoV-2, MERS-CoV, HCoV-OC43, HCoV-HKU1, HCoV-229E, and HCoV-NL63 and compared them with RNAPS in the genomes of the related animal coronaviruses including SARS-Bat-CoV, MERS-Camel-CoV, MHV, Bat-CoV MOP1, TGEV, and one of camel alphacoronaviruses. RNAPS in the genomes of coronaviruses were evolved due to weakly specific interactions between genomic RNA and N proteins in helical nucleocapsids. Combining transitional genome mapping and Jaccard correlation coefficients allows us to perform the analysis directly in terms of underlying motifs distributed over the genome. In all coronaviruses RNAPS were distributed quasi-periodically over the genome with the period about 54 nt biased to 57 nt and to 51 nt for the genomes longer and shorter than that of SARS-CoV, respectively. The comparison with the experimentally verified packaging signals for MERS-CoV, MHV, and TGEV proved that the distribution of particular motifs is strongly correlated with the packaging signals. We also found that many motifs were highly conserved in both characters and positioning on the genomes throughout the lineages that make them promising therapeutic targets. The mechanisms of encapsidation can affect the recombination and co-infection as well.
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