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Slack / Private Message Drop, p.395 [SLACK_000609] · slack_pm:msg:04083

Date: 2021-01-13 08:21
Type: chat message · slack
recipient: Robert F. Garry, Edward C. Holmes, Andrew Rambaut
speaker: Kristian G. Andersen

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This is interesting Bob. I do wonder if these are "transmission" adaptations - I believe N501Y is also often fixed after passage and we see it intrahost.As for insertions - yes, those _do_ tend to be four amino acids when we see them in SC2 - typically after culture. Why it's four, and not one, two, or three, I don't understand - probably has to do with the recombination machinerypreferring 12bp lenght.

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2021-01-13 07:39 Robert F. Garry open

Ok - !channel this is getting a bit freaky. At @Andrew Rambaut prompt I did the alignment with RmYN02. More on this later but it is very consistent with short insertions occurring between SC1 and SC2 - in fact some the overall "deletions" are larger in RmYN02. There is only one exception to the rule. Relative to SC1, SC2 and RatG13 RmYN02 has a four amino acid insertion at or around D215. @Kristian Andersen will note that insertions in SC2 are quite rare. There are however a couple of natural 4 amino acids insertions in SC2 isolates before and after D215.And just to round out the freakiness After passage in Vero we observed an 4 amino acid insert at - you guessed it -D215 Of course D215G is one of the B.1.351 defining variants. Here's the alignment: [shared file(s): image.png]
2021-01-13 07:43 Robert F. Garry open

It does look like - despite the supervillain's best efforts - SC2 keeps clawing its way back to something approachingits bat ancestor.
2021-01-13 08:21 Kristian G. Andersen

This is interesting Bob. I do wonder if these are "transmission" adaptations - I believe N501Y is also often fixed after passage and we see it intrahost.As for insertions - yes, those _do_ tend to be four amino acids when we see them in SC2 - typically after culture. Why it's four, and not one, two, or three, I don't understand - probably has to do with the recombination machinerypreferring 12bp lenght.
2021-01-13 08:35 Kristian G. Andersen open

@Andrew Rambaut - do you have a good sense of where AZN ran some of their earlier trials? Just to go back to our early crackpot theory, the emergence of these lineages also now out of Brazil makes me wonder a little... E.g.,https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)32661-1/fulltext

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