摘要
我们已从临床、流行病学和分子进化之反常等几个方面阐明了（SARS CoV的非自然起源。本文将全面深入描述SARS CoV系统发育中发生的逆向进化这一关键过程。逆向进化定义为“再获得祖先状态”，常发生在生存景观或环境的，受化使生物不适应甚至无法生存时。SARS CoV的逆向进化主要表现：①2003～2004年广州爆发SARS CoV与2002～2003年流行早期病毒之亲缘较晚期更近以及流行中SARS CoV阳性选择压逐渐下降；②在不同宿主不同流行阶段，均可发现SARS CoV受体结合位点重要氨基酸（尤其487、479二位）和SARS CoV ORF8特征性29-nt的逆向进化；③2003～2004年广州爆发病例的SARS CoV中ORF 1a基因nt.6295突变，导致SUD出现一个终止密码子，使其基因发生回复变化，不能适应人类宿主。由于SARS CoV：①离祖先病毒株仅约4年多时问，敞无法在人类亲缘关系很近的动物体内做适应试验；②迅即进入人类全新之环境，易保持祖先的永久遗传变异；③流行中阳性选择压不断降低，为逆向进化创造条件。故进人人群一年后毒力和传播力明显下降，不久即在人类和自然界消失，这是其最佳归宿。所以，其起源、进化和消失过程假设如下：蝠株（亲代3）→基因改造株1（亲代2）→基因改造株2（亲代1）→2002～2003年狸株→2002～2003年人株→2003～2004年狸株→2003～2004年人株→？→？→消失。因事关人类健康，再次吁请卫生部正式向WHO申请组织专家委员会，实证自然界和人群中已尤SARS CoV，并予宣布。
The unnatural origin of SARS CoV has been clarified in the former two articles with the unnatura evidences of clinical and epidemiological features and its unusual molecular evolution in SARS epidemic. This paper thoroughly elucidated the reverse evolution arising in SARS CoV phylogenesis, wbich is a key of analyzing its unnatural origin. The reverse evolution is defined as ＂the evolution of regaining the ancestral state＂ and frequently occurs when the organisms suffer the changes of landscapes and environments which they could not adapt well to or even not survive in. There are some important reverse evolutions of SARS CoV as follows. （1） SARS CoV in Guangzhou outbreak from late 2003 to early 2004 shows a closer relationship with that at the early phase of SARS epidemic from November 2002 to July 2003 than that at the late phase, and there is a progressive slowing of the positive selection pressures to SARS CoV over time during the whole epidemic course. （2） Reverse evolution of some critical amino acids, especially 487 and 479, at the receptor banding site of SARS CoV and Bt-SLCoV. and that of characteristic 29-nucleotide of SARS CoV and BI-SLCoV in various hosts and at different phases are observed respectively. （3） The mutation occurs in ORF la nt.6295 in SARS CoV of 2003-2004 Guangzhou outbreak, leading to a stop codon in the nsp3 CDS （SUD） of the ORF I a. Thus, some decreases of SUD function show retrieving of its genes and inadaptation of SARS CoV to the host of human population. Subsequently, SARS CoV experienced three situations. Firstly, because the time to the most recent common ancestor （tMRCA） is only about 4.5 years betbre SARS broke out, SARS CoV might not be through adaptation trial in the animals closely related to the human. Secondly, SARS CoV trended to maintain the standing genetic variation of its ancestor after it had rapidly entered lhe human host. Thirdly, the constant decrease of positive selection pressure to SARS CoV during the epidemic could create the conditions for reverse evolution. Therefore, the virulence and transmission of SARS CoV powerfully decreased one year later and soon disappeared in the human and nature, which is the best outcome lbr it. As a result, the hypothesis of the frame about the origin, evolution and disappearance of SARS CoV is as follows： Bt-SLCoV[PG （the parental generation） 3] →[GM （gene modification）l （PG 2）] →（GM 2, PG 1）→ 2002-2003 palm civet （pc-） SARS CoV → 2002-2003 human （h-） SARS CoV → 2003-2004 pc-SARS CoV → 2003-2004 h-SARS CoV → ？ → ？ → disappearance. For human health in the world, we again suggest the Ministry of Health to officially apply to WHO for organizing an expert committee to confirm and announce that SARS CoV no longer exists in nature and human population.
出处
《医学争鸣》
CAS
北大核心
2014年第1期7-12,共6页
Negative
