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Evolution of Omicron Spike S1.
Science, Vol 374, Issue 6572 red line and dots is Omicron |
Three days ago I illustrated the exceptional nature of the Omicron variant with a stunning evolutionary tree. But now I have found an even better illustration (see above). It shows the mutations Omicron accumulated in the S1 subunit of the Spike protein. It's clear: Omicron stands apart from all the other SARS-CoV-2 variants.
In addition its roots are relatively very old. The data indicate that it should have diverged from other variants as early as February 2020. That is just 2 months after the first covid-19 cases. Why did we detect Omicron only in November 2021? Where has it been hiding? Now Chinese scientists propose a new hypothesis, maybe as weird as Omicron itself: it may have been living and evolving for more than a year in a mouse population!
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Zoonotic jump from human to mouse and back. ©Gert Korthof Green virus is SARS-CoV-2 adapted to human host, Red virus is adapted to mouse host. |
They found that Omicron acquired 45 point mutations since its divergence
from the SARS-CoV-2 B.1.1 lineage. Especially the Spike protein showed an
exceptionally high number of mutations. They concluded that the Omicron spike
protein was subjected to stronger positive selection than that of any reported
SARS-CoV-2 variants known to evolve persistently in human hosts. Further, they
noted that the mutation fingerprint of Omicron was significantly different
from SARS-COV-2 viruses evolving in humans, but was highly similar to that of a virus that had evolved in
a mouse. As if the virus has been evolving in mouse populations. Omicron
seemed to be adapted to the mouse ACE2 receptor, not the human ACE2 receptor.
While the virus was living and evolving in the mouse it went undetected. So
the huge amount of new mutations in Omicron was not really a jump. Those
mutations most likely accumulated gradually in a mouse species. Apparently,
the mouse adapted Omicron seemed to be pre-adapted to the human ACE2 receptor
and started a new outbreak in humans. And it performed very well in humans.
The researchers did not claim anything specific about what mouse species was involved, or where all this happened. They did not mention South-Africa. They did not sample mouse populations in South-Africa. Their conclusion is solely based on comparing the SARS-CoV-2 RNA sequences from humans and other mammals found in public databases (GISAID, Nextstrain). The publication was posted on biorxiv.org and has not yet been peer-reviewed.
This is #38 in the Corona update series
Postscript
3 Jan 2022
The idea that the human SARS-CoV-2 could infect wild animals has shown to be happening: SARS-CoV-2 infection in free-ranging white-tailed deer (Nature, 23 Dec 2021): "that free-ranging white-tailed deer (Odocoileus virginianus) are highly susceptible to infection with SARS-CoV-2 virus, are exposed to a range of viral diversity from humans, and are capable of sustaining transmission in nature." According to NBS News after some time establishing itself in the deer population "We could be caught by surprise with a completely different variant."
My comment: that is exactly what could have happened with the Omicron variant in wild mouse populations!
Postscript
3 Feb 22
See also an article in Nature: 'Where did Omicron come from? Three key theories' paragraph 'Mouse or rat'.
Postscript
7 Feb 22
In an article in Science it is suggested that Omicron could have originated in lab mice! "(There’s no clear explanation for how Omicron arose, which has also fed some speculation the variant came from lab mice infected with SARS-CoV-2 or other research.)"
Postscript
21 dec 2022
Science: A paper [5] published earlier this month by Science claiming the Omicron variant of SARS-CoV-2 arose gradually, across a broad area of Africa, before it was detected was retracted today by its authors. ... that crucial genome sequences on which the study based its conclusions were a result of contamination
Omicron was first discovered in late 2021 in Botswana and South Africa, quickly spread across the world, and has dominated the pandemic since. Its exact origin has been a mystery, in part because Omicron is so different from the variants circulating before it. Researchers have put forth several ideas to explain the genetic gap.
- In one scenario, the virus went through an extended bout of evolution in an animal host and then spilled back into humans.
- In another, it evolved over a long period of time in a single patient with a chronic infection.
- A third possibility was that the virus had been quietly circulating and mutating in an area of the world where few viruses were being picked up and sequenced.
(it seems it is still unclear how Omicron originated)
Sources
- Kai Kupferschmidt (2021) Where did ‘weird’ Omicron come from? Science 1 Dec 2021
- Changshuo Wei et al (2021) Evidence for a mouse origin of the SARS-CoV-2 Omicron variant, 14 Dec 2021
- Gert Korthof (2021) The exceptional nature of the Omicron variant: a picture is worth a thousand words! 14 Dec 2021
- https://cov-lineages.org/lineage.html?lineage=B.1.1 There are 4 Omicron lineages listed on this page.
- Gradual emergence followed by exponential spread of the SARS-CoV-2 Omicron variant in Africa. (retracted!)
Hi Gert,
ReplyDeleteThat SARS Cov-2 Omicron is mutated in the mouse is an interesting hypothesis and perhaps very likely. But what indicates that Omicron arose from a jump from man to mouse and back again? Why is the possibility not kept open that the Omicron virus comes from the mouse directly, without having first jumped from human to mouse? You write:
"Further, they noted that the mutation fingerprint of Omicron was significantly different from SARS-COV-2 viruses evolving in humans, but was highly similar to that of a virus that had evolved in a mouse. As if the virus has been evolving in mouse populations. Omicron seemed to be adapted to the mouse ACE2 receptor, not the human ACE2 receptor."
The first jump, from human to mouse, does not seem to have been necessary.
Marleen asked: "Why is the possibility not kept open that the Omicron virus comes from the mouse directly, without having first jumped from human to mouse?"
ReplyDeleteThanks for your intriguing question. I didn't think about that possibility at all.
If true, it means that Omicron was endemic in mouse (or in other rodents/animals) in South-Africa or whatever country where the OMICRON outbreak occurred. I cannot exclude that possibility. But I don't know about data of the natural occurrances of SARS-CoV in wild animal populations.
In your scenario: was South-Africa the real origin of SARS-CoV-2? And was the virus transported with live animals to the Wuhan animal markets? and from there to the rest of the world?
And the Omicron outbreak in South-Africa was an independent secondary zoonotic event of a SARS virus that has been in the making for a year or more in wild mouse? I cannot exclude that!
Anyhow, your scenario must be compatible with the fact that the WHO classifies Omicron as B.1.1.529 variant of SARS-CoV-2, that implies it is a descendent of the Wuhan SARS-CoV-2 virus. I have no reason to doubt that. Also, Omicron's genomestructure, its genes, the order of the genes in the genome, the sequence, the genome length (30.000 bases) are typical for a genome descending from the Wuhan virus. That is the reason the authors propose the human->mouse infection event.
To be honest I don't know what '529' means in the classification scheme. Does it mean that there are 529 variants of B.1.1?
Further: the authors talk a lot about 'pre-outbreak' sequences of Omicron. They do not attach any dates to that as far as I can see. Mysterious sequences! Omicron sequences before the outbreak? ...
Gert,
ReplyDeleteI was simply wondering if, as was the case with the first SARS Cov-2 variant from Wuhan that probably jumped from bat to human, the Omicron variant didn't jump from mouse to human. A second spillover, why not? Jumping from animal to human is a similar barrier to that from human to animal, so there is no difference in probability and there is no need to assume that the future Omicron jumped from human to mouse and then again from mouse to human.
In that case, the appearance of this variant in South Africa would just be a coincidence, just as the first SARS Cov-2 variant in Wuhan was 'coincidence': it might as well have 'originated' in tropical forests from other bats, or somewhere where humans and animals live in close proximity. For example, in the case of the mouse a laboratory could be a possible location for transmission? It would be very disturbing if indeed two such serious spillovers had taken place so close to each other (2019 (Wuhan) and 2021 (South Africa))
But I can't compare the sequences and judge whether the original SARS-Cov2 and Omicron really descended from each other or arose independently. So it remains just a thought.
Marleen, I understand your theory. A second pandemic amidst an existing pandemic, is a frightening possibility! which cannot be excluded.
ReplyDeleteWell, you have to know: it is a sort of hobby of me to investigate the consequences of any interesting idea, hypothesis or theory I encounter in my life. I did it on my WDW website and I do it on my blog. The human-mouse-human zoonotic event is an example. My experience is that it delivers nearly always intellectual rewards.
For example, I started yesterday to investigate what 'B.1.1.529' (the official name of Omicron) means and I ended up on this website: cov-lineages.org and found all interesting bits of information. Surprisingly, there are indeed 529 variants in the B.1.1 lineage. Additionaly, 'B.1.1.529' and variants were not only observed in South-Africa but also in Switzerland, USA, and India on 15 Nov 2021. Oddly, on 17 Oct 2021 B.1.1.529.1 (an Omicron variant) was observed in United Kingdom! That's before the official first date of discovery in Botswana and South Africa (22 November 2021 according to wikipedia)! How odd is that?!
see:
https://cov-lineages.org/lineage.html?lineage=B.1.1.529
https://en.wikipedia.org/wiki/SARS-CoV-2_Omicron_variant
To put things in perspective: if Omicron is an independent zoonotic event, think about this fact: 'only' 60 of the 30.000 bases of Omicron differ from the Wuhan reference genome: that's 0,2% and so Omicron is 99,8% identical to the original Wuhan reference genome.
Marleen, thanks for your comments, they stimulate thinking and produce new insights!
ReplyDelete