Gallaher William R
Mockingbird Nature Research Group, Pearl River, LA, 70452, USA.
Department of Microbiology, Immunology and Parasitology, Louisiana State University Health Sciences Center, New Orleans, LA, 70112, USA.
Arch Virol. 2020 Oct;165(10):2341-2348. doi: 10.1007/s00705-020-04750-z. Epub 2020 Jul 31.
Much remains unknown concerning the origin of the novel pandemic coronavirus that has raged across the globe since emerging in Wuhan of Hubei province, near the center of the People's Republic of China, in December of 2019. All current members of the family Coronaviridae have arisen by a combination of incremental adaptive mutations, against the backdrop of many recombinational events throughout the past, rendering each a unique mosaic of RNA sequences from diverse sources. The consensus among virologists is that the base sequence of the novel coronavirus, designated SARS-CoV-2, was derived from a common ancestor of a bat coronavirus, represented by the strain RaTG13, isolated in Yunnan province in 2013. Into that ancestral genetic background, several recombination events have since occurred from other divergent bat-derived coronaviruses, resulting in localized discordance between the two. One such event left SARS-CoV-2 with a receptor binding domain (RBD) capable of binding the human ACE-2 receptor lacking in RaTG13, and a second event uniquely added to SARS-CoV-2 a site specific for furin, capable of efficient endoproteolytic cleavage and activation of the spike glycoprotein responsible for virus entry and cell fusion. This paper demonstrates by bioinformatic analysis that such recombinational events are facilitated by short oligonucleotide "breakpoint sequences", similar to CAGAC, that direct recombination naturally to certain positions in the genome at the boundaries between blocks of RNA code and potentially RNA structure. This "breakpoint sequence hypothesis" provides a natural explanation for the biogenesis of SARS-CoV-2 over time and in the wild.
自2019年12月在中国中部湖北省武汉市出现以来，肆虐全球的新型大流行冠状病毒的起源仍有许多未知之处。冠状病毒科的所有现有成员都是在过去多次重组事件的背景下，通过渐进的适应性突变组合产生的，使其成为来自不同来源的RNA序列的独特镶嵌体。病毒学家的共识是，新型冠状病毒（命名为SARS-CoV-2）的碱基序列源自一种蝙蝠冠状病毒的共同祖先，以2013年在云南省分离出的RaTG13毒株为代表。自那以后，在该祖先遗传背景中，又发生了几次来自其他不同蝙蝠来源冠状病毒的重组事件，导致两者之间出现局部不一致。其中一次事件使SARS-CoV-2具有了一个能够结合人类ACE-2受体的受体结合结构域（RBD），而RaTG13中则没有这种结构域；另一次事件则使SARS-CoV-2独特地添加了一个弗林蛋白酶特异性位点，该位点能够有效地进行内切蛋白水解切割并激活负责病毒进入和细胞融合的刺突糖蛋白。本文通过生物信息学分析表明，这种重组事件是由短寡核苷酸“断点序列”促进的，类似于CAGAC，这些序列会自然地将重组引导至基因组中RNA编码块与潜在RNA结构之间边界的某些位置。这种“断点序列假说”为SARS-CoV-2在野生环境中的长期生物发生提供了一种自然解释。
