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1. 2021-02-20 08:06 Robert F. Garry open
   "So we have a common set of functional sites/effects for all the new variants: An RdRp mutation, an nsp6 modification, spike 613/614, some NTD mutations/deletions and some RBD mutations." *Incredible* examples of convergent evolution in real-time. The fact that this emerged in Uganda with not - to my knowledge - a massive number of cases is making me think perhaps that here at least individual adaptation for viral fitness in humans >immune escape. No NellY, EeeK, etc in the A.23.1 Uganda variant, which *may* be the better signs of immune escape *or* fitness plus immune escape.
2. 2021-02-20 08:07 Andrew Rambaut open
   Will add ORF8 truncation/modification to that list.
3. 2021-02-20 08:08 Andrew Rambaut open
   @Robert Garry There is a cluster of A.23.1 that have Eeek in the UK (which is how I found it in the first place).
4. 2021-02-20 08:10 Andrew Rambaut open
   We are writing a paper about the B.1.1.7 variant including its origins and I would love to put some of this speculationin it and then perhaps lay it out in another paper. You interested in being involved? (any of you).
5. 2021-02-20 08:19 Andrew Rambaut
   My current favourite hypothesis is that all of this is about increasing transmissibility in the face of global implementation of NPI which is why we have simultaneous explosive 2nd waves (Doug & Phil) and then the 3rd waves (VOCs). In particular I am wondering if partially-effective measures may have driven evolution for transmissibility in the same way that ineffective vaccines can. Doug & Phil arose in China during the first lock down period (but possibly outside of Wuhan in somewhere like Shanghai) but really took off in Italy. Displacedeverything globally except for areas like Africa where there was not much reported incidence and not much response and lineage A persisted. Then as incidence started to rocket, NPI were implemented and the lineage AVOCs were selected for.
6. 2021-02-20 08:20 Andrew Rambaut open
   This would be an explosively political hypothesis given all the anti-lockdown stuff going on.
7. 2021-02-20 08:25 Kristian G. Andersen open
   I agree with the first part - not sure about the VOCs. I think the selection pressure there is more complicated with RSA/BRA selecting more for evasion, than inherent transmission. The fixation of mutations was probably due tointrahost selection, but I agree the near-fixation in the population likely has more to do with transmission (in apopulation with high levels of immunity - so reinfections).
8. 2021-02-20 08:27 Kristian G. Andersen open
   B.1.1.7 just looks different to me - again, mutations fixed intrahost in the first place, then near-fixation in the population because of being inherently more transmissible. I think partial immune escape adds to its success aswell.
9. 2021-02-20 08:28 Kristian G. Andersen open
   But overall, yes, I agree with the hypothesis and think the distinction of different waves being due to differentmitigation efforts is a good one - but as you say, massively politically charged.The fourth wave will likely be driven almost entirely by vaccine escape.

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