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Slack / Private Message Drop, p.536 [SLACK_000750] · slack_pm:msg:05586

Date: 2021-02-21 15:23
Type: chat message · slack
recipient: Kristian G. Andersen, Robert F. Garry, Andrew Rambaut
speaker: Edward C. Holmes

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I can certainly see that Doug & Phil increased transmissibility, but that does not explain why B.1.1.7 et al.,which arose later, are doing so well. That may have arisen through an intra-host advantage, but it's obvious that they have an epidemiological scale advantage as well. Clearly they have increased fitness which can only be due to (i)increased transmissibilty in itself....which suggests that there should other key mutations in ORF1ab (?) and/or (ii)immune evasion that enables more refection and hence increases R. Perhaps that deletion in nsp6 is the key?

In context

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2021-02-21 15:16 Kristian G. Andersen open

519 is "H" in SC2, but N in almost all other sequences - the only other deviation is K in the P378 pangolin, although that is a pretty bad sequence, so might not be real.
2021-02-21 15:16 Edward C. Holmes open

No one thinks about fixed changes: nicely blows-up the idea that SARS-CoV-2 was perfectly adapted to humans at the outset.
2021-02-21 15:18 Kristian G. Andersen open

Well, actually, this supports being perfectly adapted to humans :wink:. A in that position was fixed from the get go.
2021-02-21 15:20 Kristian G. Andersen open

(and yeah - dN/dS is shit. Just no point).
2021-02-21 15:23 Edward C. Holmes

I can certainly see that Doug & Phil increased transmissibility, but that does not explain why B.1.1.7 et al.,which arose later, are doing so well. That may have arisen through an intra-host advantage, but it's obvious that they have an epidemiological scale advantage as well. Clearly they have increased fitness which can only be due to (i)increased transmissibilty in itself....which suggests that there should other key mutations in ORF1ab (?) and/or (ii)immune evasion that enables more refection and hence increases R. Perhaps that deletion in nsp6 is the key?
2021-02-21 15:24 Edward C. Holmes open

Are there *proportionately* more chronic infections? Do we know their overall frequency?
2021-02-21 15:27 Edward C. Holmes open

Definitely needs to be set out here.
2021-02-21 15:35 Edward C. Holmes open

The Chan/Petrosky analysis was that dn/ds suggested that there was NO adaptation to humans. This shows otherwise. We know that this mutation is fixed in all the human samples studied to date, but we don't know about any chains of transmission that died out.
2021-02-21 15:43 Andrew Rambaut open

Hmm. Not sure about this paper - they are using software for detecting genomic selective sweeps using LD, I think.

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