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1. 2021-02-19 12:35 Robert F. Garry open
   To @Andrew Rambaut point above. I'm pretty sure there has been a global shift in the fitness landscape. I'm not too sure where the major selection is at the population level or the individual level or BOTH. However, I do think that the mutations at nsp12 P323 are contributing mightily to the volatility. I'm just shaking my head in disbelief. Like ascreaming read flag this amino acid is literally sitting in the groove of the RdRp complex. It surely has to affecttranscription fidelity. A deletion in nsp8 also may be a factor. [shared file(s): image.png]
2. 2021-02-19 12:35 Robert F. Garry open
   Same feeling I got when I saw the PRRA....
3. 2021-02-19 12:47 Robert F. Garry open
   Looks like it showed up early around about the time of the first DouG sightings.
4. 2021-02-19 13:12 Kristian G. Andersen open
   What's the coordinates of that mutation in ORF1a space Bob?
5. 2021-02-19 13:24 Robert F. Garry
   I think it's C14408T P4715L.
6. 2021-02-19 13:27 Kristian G. Andersen open
   ORF1b P314L? Interesting - pretty much defines Doug...
7. 2021-02-19 13:31 Robert F. Garry open
   Yeah - DouG literally opened up the stem but the nsp12 mutation may be affecting polymerase fidelity (surprising if itdidn't). Could be why @Eddie Holmes reports the volutility in trying to grow postDouG variants in cell culture.
8. 2021-02-19 13:32 Robert F. Garry open
   P323L I think.
9. 2021-02-19 13:34 Kristian G. Andersen open
   Here's Nextstrain - 323 is listed as only "K". [shared file(s): Screen Shot 2021-02-19 at 1.33.44 PM.png]

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