9 ms·

You can look at the phylogenetic tree here: https://nextstrain.org/ncov/gisaid/global https://nextstrain.org/ncov/gisaid/global with Delta being the large gre

You can look at the phylogenetic tree here: https://nextstrain.org/ncov/gisaid/global https://nextstrain.org/ncov/gisaid/global with Delta being the large green and blue parts at the top, and Omicron being a few red dots a little up from the bottom. If you trace back, you'll see that its nearest relative is wildtype from the spring of 2020. That's pretty weird, and there are really only three ways I can think of that it could happen: 1. human manipulation in a lab using early wildtype samples. This seems unlikely, because what would be the point and how did they let it escape? 2. chronic infection in a single immunosuppressed patient. We've seen this before (see, for example, this: https://www.nejm.org/doi/full/10.1056/NEJMc2031364 https://www.nejm.org/doi/full/10.1056/NEJMc2031364 ) and southern africa has a lot of immunosuppressed people thanks to HIV. Additionally, there are some genetic markers that suggest evolution in a human. 3. spillover of wildtype in spring 2020 to some animal, evolution in that population for about 17 months, then spillback last month into humans. I'm with the article, in that I favor 3 even though there's some evidence for 2 just because i can't quite understand how the omicron patient might have gone all that time without infecting anybody else with a proto-omicron version of the virus (which would then spread and be picked up on that chart). It's possible, I guess, that omicron got increased transmissability in a mutation in the recent past, and it could have lived in the patient with bad transmissability for a long time previous. And since delta is so amazingly transmissable, any proto-omicron could have infected a couple of people and then died out undetected. But still.

dhosek 5y ago
Regarding #2, it's likely that Omicron did not emerge in Africa but elsewhere. South Africa has the best genetic surveillance on the planet which is why they're picking up evidence of new variants more often than other countries.
- abrowne 5y ago
  Similarly, the second case in the US was just found in here in Minnesota, probably for the same reason (at least compared to the rest of the US). MN typically has "more" cases of seasonal diseases like flu compared to other states since our Dept of Health has been reasonably functional and funded.
- jsnell 5y ago
  That is ridiculous. South Africa has a fine program. But it's not the best of the world, or even one of the best 20 in the world. https://twitter.com/MaxCRoser/status/1465970246934749188/photo/1 https://twitter.com/MaxCRoser/status/1465970246934749188/pho... If this had been circulating in Europe, North America, or South America before Africa, we'd know. If it came from Asia or the Middle East, it'd be quite odd that it didn't get exported to Europe but just to Asia. It's overwhelmingly likely that it originated somewhere in Southern Africa, though the exact country will be anybody's guess right now.
erickhill 5y ago
Re: #3, so if you go all the way back to the original strain: Potentially animal > human > animal > omicron in humans. Like, a continuous mixing and mashing feedback loop. If nothing else, the variants occurring in real time right before our very eyes should make the idea of evolution a lot easier for some in various communities to finally grasp.
- tw04 5y ago
  >If nothing else, the variants occurring in real time right before our very eyes should make the idea of evolution a lot easier for some in various communities to finally grasp. I don't think the issue of evolution has ever been a question of people grasping the science. The issue has and continues to be the resolution of its conflict with their faith. Some have found a way through that mental obstacle course, but most have not.
  - xaduha 5y ago
    Scary number of people, not even of religious sort, think that it's perfectly fine to pick and choose which parts of scientific achievement they accept and which they don't. It's more on the scale of what they like or don't like. They might like their smartphones and other gadgets, not so much vaccines, fluoride, GMO, all that which isn't 'natural' or 'organic'. So yes, it is a question of people grasping the science, not of this specifically, but as a whole. They are not on-board, they never fully confront any contradictions that they encounter or spew. Logic is not their friend, they are not inquisitive, getting to the bottom of something is not in their nature. You might think that in general people are reasonable, but margins are not that high and informed-ness is very surface-level.
    - gmac 5y ago
      There’s certainly some deeply unscientific thinking out there … but I don’t think your examples are good ones. It’s reasonable to dislike GMOs (or some subset of them) because of who’s selling them and why, unrelated to the science. It’s reasonable to argue against fluoridated water even while accepting it’s good for dental health, because you disagree with mass medication. It’s reasonable to buy organic food if you know it to be free of certain chemicals which, knowing their scientific characteristics, you would rather avoid.
deleted 5y ago
[deleted]
ralusek 5y ago
Tinfoil hat regarding point #1: China is projected to be the single country that doesn't get Omicron. https://www.bloomberg.com/news/articles/2021-11-30/china-basks-in-covid-zero-vindication-as-omicron-closes-borders https://www.bloomberg.com/news/articles/2021-11-30/china-bas... https://time.com/6124937/omicron-china-covid-borders/ https://time.com/6124937/omicron-china-covid-borders/ https://fortune.com/2021/11/30/omicron-covid-variant-china-economy-pmi-factory-manufacturing/ https://fortune.com/2021/11/30/omicron-covid-variant-china-e... https://www.washingtonpost.com/world/asia_pacific/china-omicron-variant-coronavirus/2021/11/30/74e9788e-518d-11ec-83d2-d9dab0e23b7e_story.html https://www.washingtonpost.com/world/asia_pacific/china-omic... You get the idea. If the world stage is relative, even if the net impact is bad...it's still a positive outcome if you fare substantially better than everyone else.
- arbitrage 5y ago
  no country is not going to see a variant. especially not one as big and with as much international traffic & commerce as china.
- mikeyouse 5y ago
  The only people saying China won't get Omicron are the state newspapers in China.. of course they're going to get it. Especially since they are hosting the Olympics in ~2 months and it will certainly be the dominant strain by then.
  - whimsicalism 5y ago
    They've managed to avoid delta to a large part.
    - 14 5y ago
      I’m sure they would tell you the truth if they did have it and not down play the situation.
      - whimsicalism 5y ago
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.
hcjrmemeld 5y ago
Regarding 1., scientists already did this. This is how we know which mutations in Omicron are concerning, and which are not. They basically tried a wide range of possible mutations and tested the effect on vaccine/infection antibodies: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676316/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676316/
whimsicalism 5y ago
Could it just be that testing was so bad in Africa that we never identified this strain as it was spreading in those communities until it had some breakthrough mutation that made it much more easy to spread? I think it is telling that it was South Africa, probably one of the few SSA nations with the infrastructure to do this testing of a representative sample of their population, where this was found first.
- dnautics 5y ago
  it could be easy to find out. omicron has a very characteristic signature in the PCR test (a missing band) that I imagine makes it possible to do a retrospective analysis if you have good data records.
  - ErikCorry 5y ago
    Doesn't it share that missing band with Alpha though? There's not much Alpha around these days, so it's a good signal, but if you go back in time that would confound your search.
    - dnautics 5y ago
      I don't know, I wasn't aware of that (I am not an expert, just someone that reads slightly-more-scientific-than-mainstream-media dispatches, and can understand them having done a ton of molecular biology). If you can pont me to that I'd love to be enlightened.
      - ErikCorry 5y ago
        Alpha (aka b.1.1.7) causes S-dropout on the PCR test: https://www.medrxiv.org/content/10.1101/2020.12.24.20248814v1 https://www.medrxiv.org/content/10.1101/2020.12.24.20248814v... Omicron also causes s-dropout: https://www.bbc.com/news/health-59460252 https://www.bbc.com/news/health-59460252
ErikCorry 5y ago
I suspected spillback for Alpha because it had a bunch of intermediate mutations that were never seen in other lineages. But no animal reservoir was found and I now think the immunocompromised single patient explanation is more likely. I can see a patient that is known to have spending 6 months in a hospital bed not infecting anyone, because they are isolated and only seen by medical staff with serious protective clothing and masking. Then at some point someone slips up and it escapes. The article speculates that the animal reservoir could be rodents. If so, it's not sewer rats, at least not in one of the many countries that samples sewage to monitor outbreaks. https://journals.asm.org/doi/10.1128/mBio.02703-20 https://journals.asm.org/doi/10.1128/mBio.02703-20 By the way the transmissability of delta doesn't pose a hurdle for omicron. They are not competing, except in the sense that the severity of the delta wave makes people isolate and mask up.
etiam 5y ago
> 2. chronic infection in a single immunosuppressed patient. We've seen this before (see, for example, this: https://www.nejm.org/doi/full/10.1056/NEJMc2031364 https://www.nejm.org/doi/full/10.1056/NEJMc2031364 ) and southern africa has a lot of immunosuppressed people thanks to HIV. Additionally, there are some genetic markers that suggest evolution in a human. I speculated about this in another post recently. Might as well try putting it up for consideration here again: If it's in co-infection with HIV, then it isn't only the immune status that's abnormal in the physiology, and it might not even be the most significant circumstance with respect to what's happened here. They're not particularly closely related, but both coronaviruses and retroviruses apparently pack their genome as positive-sense, single-stranded RNA, so it doesn't seem wildly implausible to me that HIV's modifications to nucleic acid metabolism would operate on coronavirus RNA, and HIV is infamous for generating plenty of variability for itself. It copying sloppily and doing it on purpose, insofar as that can be ascribed to an organism like this. I never got particularly deep into viruses, so there may be certainly be known aspects about this I'm missing, but so far I haven't been able to find anyone to tell me a compelling reason why it wouldn't work. What are the markers that suggest evolution in a human? I'd be interested to see a reference.
- robbiep 5y ago
  Except SARS-CoV-2 also has a proof-reading lacking RNA Polymerase, and HIV infects CD4+ T cells whilst SARS-CoV-2 infects cells which express ACE2, which are numerous, but doesn’t necessarily mean a person with both infections is at all likely to have both viruses floating in the same cytoplasm. Basically, the mechanism you suggest is not necessary because the RNA Pol is just as shit as HIV’s
  - etiam 5y ago
    Thanks for the input. The shared cytoplasm condition is perfectly reasonable requirement, certainly, but it's also not a terribly high bar to clear. HIV does indeed prominently infect CD4+ T lymphocytes, but that is by no means the only cell type it infects. At the very least, both species have been described to infect macrophages (and both may display tendencies to promote cell fusion, in which case I would expect many normal categorizations of what a cell type is, are off). As for the polymerases being roughly equivalent, I have a hard time believing that. As I've understood it, coronavirus RNA polymerase does perform proofreading, and over the course of the pandemic there has been plenty of media statements of relief and optimism about SARS-CoV-2 evolution not being such a big problem because the genome seems to be relatively stable as RNA viruses go. Many of the people making those statements may have had more hopes than facts to back that up, by all means, but simply grabbing a few highly ranked search result on mutation rates (I don't have time to do a more proper review now, sorry) does seem to suggest SARS-CoV-2 was estimated to have a low mutation rate (https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7387429/ https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7387429/) at least early after the introduction to human. Admittedly, it's also reported that mutations which should be suspected to reduce the proofreading effectiveness appeared early (https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8134885/ https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8134885/). But on the other hand, HIV is change virtuoso, and one of the first things you hit with a search engine on that topic currently (https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002251 https://journals.plos.org/plosbiology/article?id=10.1371/jou...) has the following very interesting piece in the abstract: "extremely high mutation rate of (4.1 ± 1.7) × 10^{−3} per base per cell, the highest reported for any biological entity. Sequencing of plasma-derived sequences yielded a mutation frequency 44 times lower, indicating that a large fraction of viral genomes are lethally mutated and fail to reach plasma. We show that the HIV-1 reverse transcriptase contributes only 2% of mutations, whereas 98% result from editing by host cytidine deaminases of the A3 family." Evidently those cytidine deaminases act on viral DNA sequences as a host defense mechanism, so that source of mutations at least, would be distinguishing for an RNA dependent DNA polymerase such as HIV reverse transcriptase (which, by the way, apparently really doesn't do any proofreading), as compared to a coronavirus RNA dependent RNA polymerase. Now I'd be curious to see if B.1.1.529 mutations appear preferentially at positions which would have cytidine after reverse transcription. I guess that would be the guanosines in RNA original?
lamontcg 5y ago
Recombination can explain #2 pretty easily. Chronic infection produced many mutations, it also did that across many HIV infected individuals in South Africa. Those infections mutated via natural selection to avoid in-host immune responses and actually transmit poorly in the population. One of these chronically infected individuals recently came into contact with someone else that was recently infected with circulating virus. The doubly infected individual allowed Omicron to mutate via recombination and pick up mutations that allow it to spread better and so it took off. This is also more or less how animal spillback would happen as well. The animal type should be better animal-adapted and not better human-adapted. You probably need a recombination event to spill it back effectively.

dhosek 5y ago

Regarding #2, it's likely that Omicron did not emerge in Africa but elsewhere. South Africa has the best genetic surveillance on the planet which is why they're picking up evidence of new variants more often than other countries.

abrowne 5y ago
Similarly, the second case in the US was just found in here in Minnesota, probably for the same reason (at least compared to the rest of the US). MN typically has "more" cases of seasonal diseases like flu compared to other states since our Dept of Health has been reasonably functional and funded.
jsnell 5y ago
That is ridiculous. South Africa has a fine program. But it's not the best of the world, or even one of the best 20 in the world. https://twitter.com/MaxCRoser/status/1465970246934749188/photo/1 https://twitter.com/MaxCRoser/status/1465970246934749188/pho... If this had been circulating in Europe, North America, or South America before Africa, we'd know. If it came from Asia or the Middle East, it'd be quite odd that it didn't get exported to Europe but just to Asia. It's overwhelmingly likely that it originated somewhere in Southern Africa, though the exact country will be anybody's guess right now.

erickhill 5y ago

Re: #3, so if you go all the way back to the original strain: Potentially animal > human > animal > omicron in humans. Like, a continuous mixing and mashing feedback loop. If nothing else, the variants occurring in real time right before our very eyes should make the idea of evolution a lot easier for some in various communities to finally grasp.

tw04 5y ago
>If nothing else, the variants occurring in real time right before our very eyes should make the idea of evolution a lot easier for some in various communities to finally grasp. I don't think the issue of evolution has ever been a question of people grasping the science. The issue has and continues to be the resolution of its conflict with their faith. Some have found a way through that mental obstacle course, but most have not.
- xaduha 5y ago
  Scary number of people, not even of religious sort, think that it's perfectly fine to pick and choose which parts of scientific achievement they accept and which they don't. It's more on the scale of what they like or don't like. They might like their smartphones and other gadgets, not so much vaccines, fluoride, GMO, all that which isn't 'natural' or 'organic'. So yes, it is a question of people grasping the science, not of this specifically, but as a whole. They are not on-board, they never fully confront any contradictions that they encounter or spew. Logic is not their friend, they are not inquisitive, getting to the bottom of something is not in their nature. You might think that in general people are reasonable, but margins are not that high and informed-ness is very surface-level.
  - gmac 5y ago
    There’s certainly some deeply unscientific thinking out there … but I don’t think your examples are good ones. It’s reasonable to dislike GMOs (or some subset of them) because of who’s selling them and why, unrelated to the science. It’s reasonable to argue against fluoridated water even while accepting it’s good for dental health, because you disagree with mass medication. It’s reasonable to buy organic food if you know it to be free of certain chemicals which, knowing their scientific characteristics, you would rather avoid.

deleted 5y ago

[deleted]

ralusek 5y ago

Tinfoil hat regarding point #1: China is projected to be the single country that doesn't get Omicron. https://www.bloomberg.com/news/articles/2021-11-30/china-basks-in-covid-zero-vindication-as-omicron-closes-borders https://www.bloomberg.com/news/articles/2021-11-30/china-bas... https://time.com/6124937/omicron-china-covid-borders/ https://time.com/6124937/omicron-china-covid-borders/ https://fortune.com/2021/11/30/omicron-covid-variant-china-economy-pmi-factory-manufacturing/ https://fortune.com/2021/11/30/omicron-covid-variant-china-e... https://www.washingtonpost.com/world/asia_pacific/china-omicron-variant-coronavirus/2021/11/30/74e9788e-518d-11ec-83d2-d9dab0e23b7e_story.html https://www.washingtonpost.com/world/asia_pacific/china-omic... You get the idea. If the world stage is relative, even if the net impact is bad...it's still a positive outcome if you fare substantially better than everyone else.

arbitrage 5y ago
no country is not going to see a variant. especially not one as big and with as much international traffic & commerce as china.
mikeyouse 5y ago
The only people saying China won't get Omicron are the state newspapers in China.. of course they're going to get it. Especially since they are hosting the Olympics in ~2 months and it will certainly be the dominant strain by then.
- whimsicalism 5y ago
  They've managed to avoid delta to a large part.
  - 14 5y ago
    I’m sure they would tell you the truth if they did have it and not down play the situation.
    - whimsicalism 5y ago

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.

hcjrmemeld 5y ago

Regarding 1., scientists already did this. This is how we know which mutations in Omicron are concerning, and which are not. They basically tried a wide range of possible mutations and tested the effect on vaccine/infection antibodies: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676316/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7676316/

whimsicalism 5y ago

Could it just be that testing was so bad in Africa that we never identified this strain as it was spreading in those communities until it had some breakthrough mutation that made it much more easy to spread? I think it is telling that it was South Africa, probably one of the few SSA nations with the infrastructure to do this testing of a representative sample of their population, where this was found first.

dnautics 5y ago
it could be easy to find out. omicron has a very characteristic signature in the PCR test (a missing band) that I imagine makes it possible to do a retrospective analysis if you have good data records.
- ErikCorry 5y ago
  Doesn't it share that missing band with Alpha though? There's not much Alpha around these days, so it's a good signal, but if you go back in time that would confound your search.
  - dnautics 5y ago
    I don't know, I wasn't aware of that (I am not an expert, just someone that reads slightly-more-scientific-than-mainstream-media dispatches, and can understand them having done a ton of molecular biology). If you can pont me to that I'd love to be enlightened.
    - ErikCorry 5y ago
      Alpha (aka b.1.1.7) causes S-dropout on the PCR test: https://www.medrxiv.org/content/10.1101/2020.12.24.20248814v1 https://www.medrxiv.org/content/10.1101/2020.12.24.20248814v... Omicron also causes s-dropout: https://www.bbc.com/news/health-59460252 https://www.bbc.com/news/health-59460252

ErikCorry 5y ago

I suspected spillback for Alpha because it had a bunch of intermediate mutations that were never seen in other lineages. But no animal reservoir was found and I now think the immunocompromised single patient explanation is more likely. I can see a patient that is known to have spending 6 months in a hospital bed not infecting anyone, because they are isolated and only seen by medical staff with serious protective clothing and masking. Then at some point someone slips up and it escapes. The article speculates that the animal reservoir could be rodents. If so, it's not sewer rats, at least not in one of the many countries that samples sewage to monitor outbreaks. https://journals.asm.org/doi/10.1128/mBio.02703-20 https://journals.asm.org/doi/10.1128/mBio.02703-20 By the way the transmissability of delta doesn't pose a hurdle for omicron. They are not competing, except in the sense that the severity of the delta wave makes people isolate and mask up.

etiam 5y ago

> 2. chronic infection in a single immunosuppressed patient. We've seen this before (see, for example, this: https://www.nejm.org/doi/full/10.1056/NEJMc2031364 https://www.nejm.org/doi/full/10.1056/NEJMc2031364 ) and southern africa has a lot of immunosuppressed people thanks to HIV. Additionally, there are some genetic markers that suggest evolution in a human. I speculated about this in another post recently. Might as well try putting it up for consideration here again: If it's in co-infection with HIV, then it isn't only the immune status that's abnormal in the physiology, and it might not even be the most significant circumstance with respect to what's happened here. They're not particularly closely related, but both coronaviruses and retroviruses apparently pack their genome as positive-sense, single-stranded RNA, so it doesn't seem wildly implausible to me that HIV's modifications to nucleic acid metabolism would operate on coronavirus RNA, and HIV is infamous for generating plenty of variability for itself. It copying sloppily and doing it on purpose, insofar as that can be ascribed to an organism like this. I never got particularly deep into viruses, so there may be certainly be known aspects about this I'm missing, but so far I haven't been able to find anyone to tell me a compelling reason why it wouldn't work. What are the markers that suggest evolution in a human? I'd be interested to see a reference.

robbiep 5y ago
Except SARS-CoV-2 also has a proof-reading lacking RNA Polymerase, and HIV infects CD4+ T cells whilst SARS-CoV-2 infects cells which express ACE2, which are numerous, but doesn’t necessarily mean a person with both infections is at all likely to have both viruses floating in the same cytoplasm. Basically, the mechanism you suggest is not necessary because the RNA Pol is just as shit as HIV’s
- etiam 5y ago
  Thanks for the input. The shared cytoplasm condition is perfectly reasonable requirement, certainly, but it's also not a terribly high bar to clear. HIV does indeed prominently infect CD4+ T lymphocytes, but that is by no means the only cell type it infects. At the very least, both species have been described to infect macrophages (and both may display tendencies to promote cell fusion, in which case I would expect many normal categorizations of what a cell type is, are off). As for the polymerases being roughly equivalent, I have a hard time believing that. As I've understood it, coronavirus RNA polymerase does perform proofreading, and over the course of the pandemic there has been plenty of media statements of relief and optimism about SARS-CoV-2 evolution not being such a big problem because the genome seems to be relatively stable as RNA viruses go. Many of the people making those statements may have had more hopes than facts to back that up, by all means, but simply grabbing a few highly ranked search result on mutation rates (I don't have time to do a more proper review now, sorry) does seem to suggest SARS-CoV-2 was estimated to have a low mutation rate (https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7387429/ https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC7387429/) at least early after the introduction to human. Admittedly, it's also reported that mutations which should be suspected to reduce the proofreading effectiveness appeared early (https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8134885/ https://www.ncbi.nlm.nih.gov/labs/pmc/articles/PMC8134885/). But on the other hand, HIV is change virtuoso, and one of the first things you hit with a search engine on that topic currently (https://journals.plos.org/plosbiology/article?id=10.1371/journal.pbio.1002251 https://journals.plos.org/plosbiology/article?id=10.1371/jou...) has the following very interesting piece in the abstract: "extremely high mutation rate of (4.1 ± 1.7) × 10^{−3} per base per cell, the highest reported for any biological entity. Sequencing of plasma-derived sequences yielded a mutation frequency 44 times lower, indicating that a large fraction of viral genomes are lethally mutated and fail to reach plasma. We show that the HIV-1 reverse transcriptase contributes only 2% of mutations, whereas 98% result from editing by host cytidine deaminases of the A3 family." Evidently those cytidine deaminases act on viral DNA sequences as a host defense mechanism, so that source of mutations at least, would be distinguishing for an RNA dependent DNA polymerase such as HIV reverse transcriptase (which, by the way, apparently really doesn't do any proofreading), as compared to a coronavirus RNA dependent RNA polymerase. Now I'd be curious to see if B.1.1.529 mutations appear preferentially at positions which would have cytidine after reverse transcription. I guess that would be the guanosines in RNA original?

lamontcg 5y ago

Recombination can explain #2 pretty easily. Chronic infection produced many mutations, it also did that across many HIV infected individuals in South Africa. Those infections mutated via natural selection to avoid in-host immune responses and actually transmit poorly in the population. One of these chronically infected individuals recently came into contact with someone else that was recently infected with circulating virus. The doubly infected individual allowed Omicron to mutate via recombination and pick up mutations that allow it to spread better and so it took off. This is also more or less how animal spillback would happen as well. The animal type should be better animal-adapted and not better human-adapted. You probably need a recombination event to spill it back effectively.