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 1/9
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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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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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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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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 nit -
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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Thank you for this explanation! I have no training in genetics, trying to follow your argument. Does this analysis assume both RaTG13 and nCoV spent the same time in the wild? Suppose, nCoV line was preserved for several years in a lab, would your argument still hold?
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It’s a good question. The genetic data support both RaTG13 and nCoV spending equal amounts of time “in the wild”. This is because they each have ~550 nucleotide mutations from common ancestor. This doesn’t make freezer impossible, but there is no evidence for such.
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Yes. I also found a significantly stronger purifying selection of spike on both bat->sars and bat->nCoV lineages than among bats using a simple PAML branch model. It's opposite to my expectation...
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