2019新型冠状病毒基因组的生物信息学分析

Bioinformatics analysis of the 2019 novel coronavirus genome

2019年12月,中国武汉报道了冠状病毒引起的肺炎,其临床症状与2003年爆发的严重急性呼吸综合征(Severe Acute Respiratory Syndrome,SARS)不同,因此推断该病毒可能是冠状病毒的一个新变种。不同于简单使用全基因组序列的其它研究,我们于2018年在国际上首次提出分子功能与进化分析相结合的研究思想,并应用于Beta冠状病毒B亚群(BB冠状病毒)基因组的研究。在这一思想指导下,本研究使用BB冠状病毒基因组中的一个互补回文序列(命名为Nankai complemented palindrome)与其所在的编码区(命名为Nankai CDS)对新发布的2019新型冠状病毒基因组(GenBank:MN908947)进行分析以期准确溯源,并对BB冠状病毒的跨物种传播和宿主适应性进行初步研究。溯源分析的结果支持2019新型冠状病毒源自蝙蝠,但与SARS冠状病毒差异巨大,这一结果与两者临床症状差异一致。本研究的最重要发现是BB冠状病毒存在大量的可变翻译,从分子水平揭示了BB冠状病毒变异快、多样性高的特点。从BB冠状病毒可变翻译中获取的信息可应用于(但不限于)其快速检测、基因分型、疫苗开发以及药物设计。另外,我们推断BB冠状病毒可能通过可变翻译以适应不同宿主。基于大量基因组数据的实证分析,本研究在国际上首次从分子水平尝试解释了BB冠状病毒变异快、宿主多且具有较强的宿主适应性的原因。

In December 2019,a pneumonia outbreak caused by a human coronavirus was reported in Wuhan(China).This virus was predicted as a new coronavirus,named the 2019 novel coronavirus(2019-nCoV),as it caused clinical symptoms different from Severe Acute Respiratory Syndrome(SARS)during the 2003 outbreak.Currently,most of the researchers simply use the complete genome or specific structural gene sequences to investigate coronavirus(e.g.phylogenetic analysis)without considering the functions of the products from coronavirus genes.To overcome this shortcoming,we proposed the joint analysis of the molecular function and phylogeny,and applied it in our previous study of genomes of Betacoronavirus subgroup B(BB coronavirus).In that study,we identified a 22-bp complemented palindrome from a highly conserved Coding Sequence(CDS).Both the 22-bp complemented palindrome(named Nankai complemented palindrome)and the CDS(named Nankai CDS),evolutionary conserved in BB coronavirus genomes,were identified as genomic features associated to the molecular functions of BB coronavirus.In the present study,we used these two genomic features to trace the origin of 2019-nCoV(GenBank:MN908947)and conduct a preliminary study of the mechanisms in the cross-species infection and host adaption of BB coronavirus.Our analytical results show that 2019-nCoV with large differences from the SARS coronavirus,may originate from BB coronaviruses in bats.The most important finding is that the alternative translation of Nankai CDS could produce more than 17 putative proteins,which may be responsible for the host adaption.The genotyping of 13 viruses using the 17 putative proteins revealed the high mutation rate and diversity of BB coronavirus.Our study,for the first time,aimed to explain the reason for the high host adaptability of the multi-host BB coronavirus at the molecular level using large amounts of genomic data.The findings in the present study laid foundations for the rapid detection,genotyping,vaccine development and drug design of,but not limited to BB coronavirus.