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If you'd like to investigate yourself, you can either run the entire openly available bioinformatics pipeline here https://github.com/blab/sars-like-cov … or just work from the resulting JSON file that contains all of these mutation calls here https://raw.githubusercontent.com/blab/sars-like-cov/master/auspice/sars-like-cov.json …
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Looking at mutation distributions, it appears that the genetic differences in
#nCoV2019 are consistent with differences expected to arise during natural evolution, as I would expect engineering to have a distorted AA to nuc ratio and to focus on changing a subset of genes 9/9Prikaži ovu nitHvala. Twitter će to iskoristiti za poboljšanje vaše vremenske crte. PoništiPoništi -
Additionally, I thought to look at the distribution of amino acid changes across genes in the virus genome. In this case, we see highly similar distributions between the nCoV lineage and its closest bat virus relative. 8/9pic.twitter.com/oLyZPHSNgy
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And in fact we see that the RaTG13 lineage has 79 amino acid changes and 563 nucleotide changes for a ratio of 14.2%. Thus we see that the outbreak virus has a similar distribution of nucleotide vs amino acid changes as its closest bat virus relative. 7/9pic.twitter.com/Uw2Evu9qTo
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Evolutionary biologists commonly use the ratio of amino acid changes to nucleotide changes to look for natural selection (https://en.wikipedia.org/wiki/Ka/Ks_ratio …). Observing 14% of changes as amino acid changes fits with common expectations for sequences evolving under purifying selection. 6/9
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The
#nCoV2019 lineage has 79 amino acid changes and 554 nucleotide changes relative to this common ancestor, so that only 14.3% of changes result in differences in amino acid. 5/9Prikaži ovu nitHvala. Twitter će to iskoristiti za poboljšanje vaše vremenske crte. PoništiPoništi -
These two viruses are separated by ~1100 nucleotide changes, consistent with 20-70 years of evolution between them (assuming an evolutionary rate of between 3x10^-4 and 1x10^-3 subs per site per year). This suggests a common ancestor in bats between 1950 and 2000. 4/9
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The nCoV lineage is shown as a dashed line under the "nCoV" label (lower right). The RaTG13 lineage is shown as a dashed line above the "RaTG13" label (also lower right). 3/9pic.twitter.com/SGYigEXAFy
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I used the evolutionary tree here https://nextstrain.org/groups/blab/sars-like-cov … and the bioinformatic pipeline here https://github.com/blab/sars-like-cov … to identify mutations leading to
#nCoV2019 and also identify mutations leading to bat virus RaTG13, which is its closest sequenced relative. 2/9Prikaži ovu nitHvala. Twitter će to iskoristiti za poboljšanje vaše vremenske crte. PoništiPoništi -
I thought to examine signal of natural evolution in
#nCoV2019 by looking at distribution of mutations in the lineage leading to nCoV and compare this distribution to mutations occurring in other SARS-like bat viruses 1/9Prikaži ovu nitHvala. Twitter će to iskoristiti za poboljšanje vaše vremenske crte. PoništiPoništi -
Trevor Bedford proslijedio/la je Tweet
https://nextstrain.org/ncov has been updated with one new
#nCoV2019 genome (Zhejiang/Hangzhou-1/2020) sampled Jan 21 in Zhejiang and shared by the Hangzhou CDC Microbiology Lab. It's consistent with a direct export from Wuhan.pic.twitter.com/4ZNy2BEY4F
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I've further outlined evidence against this paper in the following thread:https://twitter.com/trvrb/status/1223666856923291648 …
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Again, there is absolutely no evidence for either (1) sequence insertions or (2) their relationship to HIV. If you'd like to look at the alignment yourself, I've posted it here: https://trvrb.s3.amazonaws.com/sars-like-spike-alignment.fasta … 9/9
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"Insert 4" (QTNSPRRA) shares GTNS with the bat virus RaTG13, while PRRA represents unique material in
#nCoV2019. This is a tiny tiny sequence and in no way suggests engineering. This sorts of small indels occur all the time in natural evolution of SARS-like coronaviruses. 8/9pic.twitter.com/w7K9Ca8xHQ
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"Insert 3" (GDSSSG) also appears to be a possible alignment artifact, though this is equivocal. However, this "insert" is most definitely in RaTG13. There was no insertion of RNA into the
#nCoV2019 spike protein. 7/9pic.twitter.com/3bW16ZG2UC
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We see that "insert 2" (YYHKNNKS) doesn't appear to be an insertion at all, but an alignment artifact of the authors. Also, it is present in the closest bat virus RaTG13 with related sequences in closely related viruses. No way this is an insertion into
#nCoV2019. 6/9pic.twitter.com/jUkVSY9nD3
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Looking at each "insert" in turn. We see that "insert 1" (GTNGTKR) is present in the closely related virus bat/Yunnan/RaTG13/2013. It is impossible that this sequence was "inserted" into the
#nCoV2019 genome. 5/9pic.twitter.com/ziizAGv7d5
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Here, I include additional SARS-like viruses in an alignment of spike protein to show that these "inserts" are nothing of the sort proposed by the paper and instead arose naturally in the ancestral bat virus 4/9
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#nCoV2019 is a member of the SARS-like virus family. These circulate naturally in bats and undergo all sorts of evolution during this natural circulation. Two of these viruses (SARS in 2002-03 and nCoV in 2019-20) have spilled over into the human population causing outbreaks. 3/9pic.twitter.com/YjeZPoRuug
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This paper proposes that there are 4 short "insertions" in the spike protein in
#nCoV2019 copied from HIV. Yesterday, I showed that the proposed inserts are tiny strings that randomly match a whole bunch of things. 2/9https://twitter.com/trvrb/status/1223337991168380928 …
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