生物与医学2022frontiersin.org
SARS-CoV-2 含有一段受专利保护的基因序列
SARS-CoV-2 contains part of a patented genetic sequence
进阶 · 约 45 分钟读完前置知识：分子生物学基础、BLAST 序列比对、冠状病毒基因组结构
导读
这篇论文声称在 SARS-CoV-2 基因组中发现了一段 19 个核苷酸的序列，与 Moderna 早期一项专利中的基因序列 100% 匹配，且在 BLAST 数据库中未在其他真核或病毒基因组中找到。论文据此提出该片段来源值得进一步研究。
HN 关注点：该论文暗示病毒基因组与专利序列吻合，触及实验室泄漏 vs 自然起源这一 HN 读者高度关注的敏感话题，评论区焦点集中在论文方法是否可靠、结论是否被夸大。
HN 评论精选
这几条评论里：质疑 2 补充 1 亲历 1
质疑亲自复现 BLAST 搜索，指出论文「未找到匹配」的核心论断不成立
「除了 SARS-CoV-2，我们在 BLAST 数据库中未在任何真核或病毒基因组中找到这段 19 核苷酸序列。」——什么？我刚用 blastn 跑了这段序列，就在多个真核基因组中找到了 100% 覆盖、100% 一致性的匹配。而且根本不存在所谓「BLAST 数据库」（BLAST 只是工具名，我用的是 nr 库）。他们没找到的可能原因是 BLAST 默认只返回前 100 条命中，而那些可能恰好是原核生物的。
flobosg查看英文原文
> We did not find the 19-nucleotide sequence CTCCTCGGCGGGCACGTAG in any eukaryotic or viral genomes except SARS-CoV-2 with 100% coverage and identity in the BLAST database (Supplementary Tables 1–3). Huh? I just run BLAST (blastn, specifically) with that nucleotide sequence and found several eukaryotic genomes containing it in non MutS-like contexts, aligning sense and anti-sense strands, with 100% coverage and 100% identity. Besides, there is no “BLAST” database (I used the non-redundant -nr- one, for instance; BLAST is just the name of the tool). One possible reason they didn’t find the sequences is that BLAST, by default, only returns the first 100 hits, which in their case might have been prokaryotic ones. I didn’t check viral genomes but might later. Disclaimer: I know and have used BLAST since my undergrad years, about a decade and a half ago.
质疑专业质疑：弗林切割位点在祖先冠状病毒中已存在，短序列 BLAST 匹配无统计意义
我是分子生物学家但不是病毒学家。这篇文章很愚蠢。几乎相同的弗林蛋白酶切割位点序列存在于多个 SARS-CoV-2 的祖先冠状病毒中（附文献链接）。2020 年严肃的病毒学家已详细研究过该位点，没人认为它不是自然产生的。另外，把任意 13 bp 的 DNA 序列丢进 BLAST，选对数据库总能找到奇怪的匹配；这段序列反向匹配人类基因组某处并不奇怪。
ImaCake查看英文原文
I am a molecular biologist but not a virologist. This article is stupid. The furin cleavage site, with almost identical sequences is present in several ancestral coronaviruses to Sars cov II. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7836551/ Serious virologists went over the furin cleavage site in close detail already and none of them seemed very convinced it was anything but natural in 2020. Also, stick any 13 bp dna sequence into BLAST and you will find some strange matches if you include the right databases. That this particular 13 base pairs matches some bit of the human genome (inverted, mind you) is not really that surprising.
补充指出论文结论早有先例，且未引用或致谢原始提出者
有趣的是，这个观察几个月前就在一篇 Substack 文章（arkmedic）中被提出过。我没有看到该作者出现在论文作者或参考文献中，不知道是独立发现还是有过合作。那篇 Substack 五周前曾在这里引发大量讨论，虽然文章本身被批评写得很差，但对观察本身的讨论应该与此相关。
matheweis查看英文原文
Interestingly, the observation in this paper was surfaced on a substack several months ago. https://arkmedic.substack.com/p/how-to-blast-your-way-to-the-truth I do not see the substack author among the paper authors or references to that writeup. I wonder if there was any collaboration or if this was an independent finding? That substack made the rounds here about 5 weeks ago. While it was heavily critiqued for being a rather poor writeup, there was a fair bit of discussion about the observation itself that should be relevant here: https://news.ycombinator.com/item?id=29938732
亲历转述系统发育分析者的亲历观点，称病毒不同区域演化历史不一致
这事早就有人知道了。我有个做群体遗传学、整天做系统发育分析的好朋友，他一直在分析已发表的序列，个人结论是 SARS-CoV-2 不可能是「自然」产生的。他还认为病毒似乎没有单一的「起源」：正常情况下系统发育应满足类似 A→B、B→C 则 A→C 的树状结构规则，但 SARS-CoV-2 的不同区域似乎没有遵循相同的演化历史，这很奇怪。这种现象在自然界也观察到过，但需要非常特殊的条件。
moralestapia查看英文原文
This has been known for a while, but I'm not complaining about it. Ever since this whole thing started, several scientists have been finding things which are "interesting to take a look into them further", to put it in some way. I have a close friend who works w/ population genetics and basically does phylogenies all day. For those who don't know, a phylogeny is an analysis where you study how similar/dissimilar are sequences between known things in order to infer what are the most plausible evolutionary relationships that (could have) happened. So, this friend of mine has been taking a look at some of the published sequences ever since they came out and his personal conclusion is that there is no way that SARS-CoV-2 came to be in a "natural" way. Among other interesting things, he claims that the virus does not seem to have a single "origin". I'll try to explain, so while you're figuring out what the "history" of something is (i.e. ancestors, lineage), you usually get some sort of tree-like arrangement where some structural rules are strongly (but not completely) preserved, like if A -> B and B -> C then A -> C, you get the idea. In SARS-CoV-2's case, such rules (or lack thereof) suggest that different regions of the sequence cannot be assumed to have followed the same evolutionary history; which is kind of weird, honestly. This is something that has been observed naturally, but under very specific constraints which are unlikely to apply to SARS-CoV-2 and how it has spread throughout the world. Anyway, I'm happy that these sort of studies are finally coming to light and that, for whatever reason, people are now allowed to talk about it. The whole point of science is to engage in rational discussion and build on each other's knowledge in order to attain the truth. PS: I have degrees in Genomics and Molecular Biology, and have worked for around 15 years on the field.
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