Slack / Private Message Drop — page 536

Did you see this: https://www.biorxiv.org/content/10.1101/2021.02.13.431090v1.full.pdf+html [2021-02-21 15:09:54] [Eddie Holmes] I've not read it carefully yet, but interesting to see the adaptive changes in ORF1ab as well. They are dead right that dN/dS is pretty rubbish when you have fixed mutations. [2021-02-21 15:12:34] [Kristian Andersen] Yeah, just saw it too - pretty interesting. And yes, "A" is totally unique to SC2 there [2021-02-21 15:13:39] [Eddie Holmes] [thread - ID: 2021-02-20 08:10:32] I'm in...sorry, just catching up this thread now. [2021-02-21 15:14:15] [Kristian Andersen] it's nicely spotted, since it's the only mutation unique to SC2 in the RBD - we should have picked this up earlier. I wonder if H519 does something interesting too. [2021-02-21 15:16:23] [Kristian Andersen] 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 15:16:38] [Eddie Holmes] 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 15:18:13] [Kristian Andersen] [thread - ID: 2021-02-21 15:18:13] Well, actually, this supports being perfectly adapted to humans :wink:. A in that position was fixed from the get go. [2021-02-21 15:20:18] [Kristian Andersen] (and yeah - dN/dS is shit. Just no point). [2021-02-21 15:23:31] [Eddie Holmes] [thread - ID: 2021-02-20 08:27:16] 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 15:24:56] [Eddie Holmes] [thread - ID: 2021-02-20 09:23:53] Are there *proportionately* more chronic infections? Do we know their overall frequency? [2021-02-21 15:27:17]