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Your options are fine, but nowhere near a comprehensive set. You left out an obvious option, for example: 4. Evolution of a lineage that we didn't detect until

by timr 5y ago

Your options are fine, but nowhere near a comprehensive set. You left out an obvious option, for example: 4. Evolution of a lineage that we didn't detect until now because it wasn't common. We need to stop making the assumption that our surveillance systems are comprehensive. They're pretty bad, actually -- and they're generally incredibly biased in what they're looking at. Even if we were doing unbiased random sampling and sequencing, we'd have to do huge volumes of it to reliably detect rare strains. (aside: and if we did do that, we'd be in non-stop panic mode, because we'd be finding a new strain every day.)

onychomys 5y ago
But we'd have to be missing a huge number of related strains to make the phylogeny look like that. The important thing isn't that we found a new strain now, it's that the strain is most closely related to very early wildtype.
- nostrademons 5y ago
  Or the population that it evolved in is isolated, so it never escaped back into the developed world until now. Somewhat unlikely given how interconnected the world is now, but it is Africa after all.
- whimsicalism 5y ago
  Well yeah, many of the places with the worst testing coverage are probably close to each other geographically.
- timr 5y ago
  > But we'd have to be missing a huge number of related strains to make the phylogeny look like that Define "huge". There are about ~30 mutations on the spike protein from the closest known relative, and there's a fairly strong selective pressure against the wild type (both from vaccine and natural infection). I think it's quite probable that we missed a few months of evolution of a strain circulating in a single-digit percentage of people. This is particularly true when you consider that this strain has S-gene dropout (Delta does not), and was probably dismissed as Beta and never targeted for sequencing by most labs. That's why I meant by my original comment that we're biased about what we look at.
ErikCorry 5y ago
Denmark and Iceland sequence every single positive sample. Currently 4k per day for Denmark. So I think there's more surveillance than you think.
- timr 5y ago
  Yeah, some do. But consider that there are at least millions of new infections a day, globally...
  - downWidOutaFite 5y ago
    Also consider how interconnected the world is that Delta spread around the globe in a few months.
    - timr 5y ago
      Oh, definitely. It's fairly obvious to anyone who understands molecular clocks that this strain is already widely spread. We're panicking and closing borders and doing untold damage because...we continue to overestimate our ability to see what nature is doing in an unbiased way.
dkonofalski 5y ago
That wouldn't happen, even with our substandard testing, unless the strain somehow had very low ability for transmission and then only evolved that in this last jump which is not likely. Since there are multiple variations from the older strain, we'd have seen at least some of the new variations along the way.
manojlds 5y ago
I still can't believe that US, where it's been rampant, hasn't been a place to report a new variant of concern for the first time, but UK, India, SA (and other like Peru?) have.

by timr 5y ago

onychomys 5y ago

But we'd have to be missing a huge number of related strains to make the phylogeny look like that. The important thing isn't that we found a new strain now, it's that the strain is most closely related to very early wildtype.

nostrademons 5y ago
Or the population that it evolved in is isolated, so it never escaped back into the developed world until now. Somewhat unlikely given how interconnected the world is now, but it is Africa after all.
whimsicalism 5y ago
Well yeah, many of the places with the worst testing coverage are probably close to each other geographically.
timr 5y ago
> But we'd have to be missing a huge number of related strains to make the phylogeny look like that Define "huge". There are about ~30 mutations on the spike protein from the closest known relative, and there's a fairly strong selective pressure against the wild type (both from vaccine and natural infection). I think it's quite probable that we missed a few months of evolution of a strain circulating in a single-digit percentage of people. This is particularly true when you consider that this strain has S-gene dropout (Delta does not), and was probably dismissed as Beta and never targeted for sequencing by most labs. That's why I meant by my original comment that we're biased about what we look at.

ErikCorry 5y ago

Denmark and Iceland sequence every single positive sample. Currently 4k per day for Denmark. So I think there's more surveillance than you think.

timr 5y ago
Yeah, some do. But consider that there are at least millions of new infections a day, globally...
- downWidOutaFite 5y ago
  Also consider how interconnected the world is that Delta spread around the globe in a few months.
  - timr 5y ago
    Oh, definitely. It's fairly obvious to anyone who understands molecular clocks that this strain is already widely spread. We're panicking and closing borders and doing untold damage because...we continue to overestimate our ability to see what nature is doing in an unbiased way.

dkonofalski 5y ago

That wouldn't happen, even with our substandard testing, unless the strain somehow had very low ability for transmission and then only evolved that in this last jump which is not likely. Since there are multiple variations from the older strain, we'd have seen at least some of the new variations along the way.

manojlds 5y ago

I still can't believe that US, where it's been rampant, hasn't been a place to report a new variant of concern for the first time, but UK, India, SA (and other like Peru?) have.