The Early Cryptic Transmission and Evolution of SARS-CoV-2 in Human Hosts Citation DataSSRN Electronic Journal
Article Description SummaryBackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is first identified in Wuhan City at the end of December 2019 and responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. So far this pandemic has claimed more than one million lives all over the world and its origin is still unknown.MethodsIn this study, we developed a method to search the least mutated strain using SARS-CoV-2 whole genome sequences. By parsimony principle, the least mutated strain should be the phylogenetic root for all SARS-CoV-2s. We further investigated the SARS-CoV-2’s adaptive evolutionary process in human hosts using the least mutated strain as the phylogenetic root and analyzed its strain diversity in different countries/regions.FindingsAccording to their coding region identity, we classified 4571 SARS-CoV-2 genome sequences into 2449 viral strains collected from human hosts between December 2019 and July 2020. We found that the SARS-CoV-2 (NC_045512) strain first identified in Wuhan is not the least mutated strain. There are 41 SARS-CoV-2 strains harboring fewer global point mutations than the NC_045512 strain in our dataset. The least mutated strain can be found in eight countries across four continents due to SARS-CoV-2’s low mutability. Eight positive selection sites are identified in five SARS-CoV-2’s genes and four of them were present in the early stage of SARS-CoV-2’s human-to-human transmission. The NC_045512 strain has two positive selection sites, one in RNA-dependent RNA polymerase (L314P) and the other in spike protein (G614D). The statistical analysis of the SARS-CoV-2’s strain diversity in different countries/regions shows that the Indian subcontinent has the highest strain diversity. Furthermore, based on the SARS-CoV-2’s mutation rate, we estimate that the earliest SARS-CoV-2 transmission in human hosts could be traced back to July or August of 2019.InterpretationOur result shows that Wuhan is not the place where human-to-human SARS-CoV-2 transmission first happened. Before it spread to Wuhan, SARS-CoV-2 has already experienced adaptive evolution during its human-to- human transmission. The positive selection sites could contribute to the different clinical features of different SARS-CoV-2 strains. Both the least mutated strain’s geographic information and the strain diversity suggest that the Indian subcontinent might be the place where the earliest human-to-human SARS-CoV-2 transmission occurred, which was three or four months prior to the Wuhan outbreak. Our study helps to elucidate the early cryptic transmission and evolution of SARS-CoV-2 in human hosts and provide the new thinking for the global management of the COVID-19 pandemic.
国际权威医学杂志《柳叶刀》的预印本平台ssrn.com近日发表一篇论文，指出印度次大陆可能是新冠病毒最早发生人与人之间传播的地点。香港《南华早报》称，这项研究的一部分经过了同行评审，并发表在《分子系统发育与进化》杂志上。印度政府学者否定该论文的准确性，但没有给出详细解释。
ssrn.com网站显示，该论文发表于11月17日，列出了3位作者，分别是来自中国科学院
的Libing Shen、复旦大学生命科学学院的Funan He和美国得克萨斯大学休斯敦生物科
学与分子生物学院的Zhao Zhang，论文题为“新冠病毒在人类宿主中的早期秘密传播和进化”，共22页。
《南华早报》称，Shen的团队说，追踪冠状病毒株起源的传统方法——一种称为系统发育分析的方法——不起作用。他们使用了一种新方法，只计算每个病毒株中的突变数。具有更多突变的菌株已经存在了更长时间，而具有更少突变的菌株更接近于新冠病毒的原始祖先。研究小组发现，某些菌株的突变少于在武汉首次采集的菌株。它得出结论：武汉不可能是新冠病毒在人与人之间传播的第一个地方。该论文还指出，在四大洲的8
个国家中发现了突变最少的菌株：澳大利亚、孟加拉国、希腊、美国、俄罗斯、意大利、印度和捷克。但是病毒不可能在这些地方同时传播给人类，第一次暴发的地区应该具有最多的遗传多样性，表明它已经存在了更长时间。研究人员发现，印度和孟加拉国的菌株拥有最多的病毒多样性。该论文认为：“突变最少的菌株的地理信息和菌株多样性均表明，印度次大陆可能是最早发生人与人之间新冠病毒传播的地方。”基于新冠病毒的突变率，该研究估计人类宿主中最早的新冠病毒传播可追溯到2019年7月或8月。Shen和同事说，极端天气可能引发了大流行。2019年5月，印度发生长期高温天气，干旱迫
使动物和人类饮用相同的水，这可能增加了病毒传播给人类的机会。
该发现引发国际媒体议论。英国《卫报》29日将其归结于“中国试图改变新冠病毒叙事”。《南华早报》称，有科学家质疑该发现，印度政府病毒学家Mukesh Thakur称不同
意该研究的结论，但没有进一步阐述。英国《每日邮报》引述格拉斯哥大学教授David Robertson的话称，该研究“有缺憾”，其做法“本质上有偏见”。加州大学洛杉矶分
校（UCLA）人类遗传学和生物统计学教授Marc Suchard说，“任意收集的”病毒株“不太可能产生祖细胞”，他承认该研究方法“有很大希望”，但表示“存在很大的不确定性”。Shen对《南华早报》称，他欢迎各界对该论文进行探讨。
新冠疫情发生以来，病毒溯源问题一直受到高度关注，国际上不断出现关于疫情暴发时间、地点的报道。中国外交部发言人多次表示，病毒溯源是复杂的科学问题，应由科学家在全球范围开展国际科学研究与合作，这是一个持续发展的过程，可能涉及多国多地。中方希望各国都采取积极态度，同世卫组织等加强合作，推进全球溯源工作。
不是说澳大利亚森林大火导致数百万蝙蝠进城吗？
该文已经下架了。
【 在 benci (ainiyou) 的大作中提到: 】
: http://www.mitbbs.com/pic_home/weiyan/pic/M/mitbbs3/74485/4.jpg
: 国际权威医学杂志《柳叶刀》的预印本平台ssrn.com近日发表一篇论文，指出印度次大
: 陆可能是新冠病毒最早发生人与人之间传播的地点。香港《南华早报》称，这项研究的
: 一部分经过了同行评审，并发表在《分子系统发育与进化》杂志上。印度政府学者否定
: 该论文的准确性，但没有给出详细解释。
: ssrn.com网站显示，该论文发表于11月17日，列出了3位作者，分别是来自中国科学院
: 的Libing Shen、复旦大学生命科学学院的Funan He和美国得克萨斯大学休斯敦生物科
: 学与分子生物学院的Zhao Zhang，论文题为“新冠病毒在人类宿主中的早期秘密传播和
: 进化”，共22页。
: 《南华早报》称，Shen的团队说，追踪冠状病毒株起源的传统方法——一种称为系统发
: ...................
为什么下架了？
【 在 comeandgo (春困秋乏夏打盹) 的大作中提到: 】
: 该文已经下架了。
who knows? maybe Lancet felt the heat.
【 在 dIdT (星垂平野阔) 的大作中提到: 】
: 为什么下架了？
还真下了，点进去文章已经没了。
【 在 comeandgo (春困秋乏夏打盹) 的大作中提到: 】
: 该文已经下架了。
可笑白皮所谓“学术自由”的画皮又被撕下来一次
尼玛。竟然下架了。
不过文章是传出来了，以后证明方法是可靠的，还可以重新发，平反昭雪。
这个不太可能。文章本身有问题。早下早好。
【 在 futurist (展望未来) 的大作中提到: 】
: 尼玛。竟然下架了。
: 不过文章是传出来了，以后证明方法是可靠的，还可以重新发，平反昭雪。
【 在 StMicheal (archangel) 的大作中提到: 】
: 这个不太可能。文章本身有问题。早下早好。
https://plu.mx/ssrn/a/?ssrn_id=3724275
The Early Cryptic Transmission and Evolution of SARS-CoV-2 in Human Hosts
Citation DataSSRN Electronic Journal
Article Description
SummaryBackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is first identified in Wuhan City at the end of December 2019 and
responsible for the ongoing coronavirus disease 2019 (COVID-19) pandemic. So far this pandemic has claimed more than one million lives all over the
world and its origin is still unknown.MethodsIn this study, we developed a
method to search the least mutated strain using SARS-CoV-2 whole genome
sequences. By parsimony principle, the least mutated strain should be the
phylogenetic root for all SARS-CoV-2s. We further investigated the SARS-CoV-2’s adaptive evolutionary process in human hosts using the least mutated
strain as the phylogenetic root and analyzed its strain diversity in
different countries/regions.FindingsAccording to their coding region
identity, we classified 4571 SARS-CoV-2 genome sequences into 2449 viral
strains collected from human hosts between December 2019 and July 2020. We
found that the SARS-CoV-2 (NC_045512) strain first identified in Wuhan is
not the least mutated strain. There are 41 SARS-CoV-2 strains harboring
fewer global point mutations than the NC_045512 strain in our dataset. The
least mutated strain can be found in eight countries across four continents due to SARS-CoV-2’s low mutability. Eight positive selection sites are
identified in five SARS-CoV-2’s genes and four of them were present in the early stage of SARS-CoV-2’s human-to-human transmission. The NC_045512
strain has two positive selection sites, one in RNA-dependent RNA polymerase (L314P) and the other in spike protein (G614D). The statistical analysis of the SARS-CoV-2’s strain diversity in different countries/regions shows
that the Indian subcontinent has the highest strain diversity. Furthermore, based on the SARS-CoV-2’s mutation rate, we estimate that the earliest SARS-CoV-2 transmission in human hosts could be traced back to July or August of 2019.InterpretationOur result shows that Wuhan is not the place where human-to-human SARS-CoV-2 transmission first happened. Before it spread to Wuhan, SARS-CoV-2 has already experienced adaptive evolution during its human-to-
human transmission. The positive selection sites could contribute to the
different clinical features of different SARS-CoV-2 strains. Both the least mutated strain’s geographic information and the strain diversity suggest
that the Indian subcontinent might be the place where the earliest human-to-human SARS-CoV-2 transmission occurred, which was three or four months prior to the Wuhan outbreak. Our study helps to elucidate the early cryptic
transmission and evolution of SARS-CoV-2 in human hosts and provide the new thinking for the global management of the COVID-19 pandemic.