- The origin of the Omicron variant of SARS-CoV-2 is uncertain because it contains a large number of mutations that are rare in other known human variants.
- The most popular theory is that Omicron evolved during a protracted infection of an individual with a compromised immune system.
- Scientists at the Chinese Academy of Sciences now report that they have found a pattern of mutations in Omicron that is typical of a virus that has infected mice.
- They believe SARS-CoV-2 jumped from a human to a mouse in mid-2020, then back into a human in late 2021.
- They say it is unlikely that the intermediate host was a laboratory mouse.
On November 24, 2021, scientists in South Africa revealed that they had discovered a worrying new variant of SARS-CoV-2.
They reported that the variant was spreading very rapidly in southern Africa and contained a large number of unusual mutations likely to make the virus more infectious than previous variants.
Within days of the scientists’ announcement, the World Health Organization (WHO) declared that the new variant, called Omicron, was a variant of concern.
Confirming the scientists’ early fears, by early January 2022, Omicron was driving an unprecedented surge in cases worldwide.
Many of the mutations that health experts identified in Omicron are rare among previously sequenced variants of the virus.
This presents a puzzle for scientists because there are no known intermediate variants to reveal how Omicron evolved. It is almost as if the new variant appeared “out of nowhere.”
There are three alternative theories for the origin of Omicron:
- The variant evolved undetected in a population somewhere in the world where there was little COVID-19 surveillance and sequencing.
- It evolved in someone who remained with the infection for an unusually long time because their immunity was compromised, perhaps as a result of a concurrent HIV infection or treatment with an immune-suppressing drug.
- It evolved in an animal population before a human acquired the virus.
The second theory is the most popular among virologists and epidemiologists.
However, some experts have argued that other viruses, such as the influenza virus, tend to become less infectious over time in individuals with compromised immune systems.
They cite evidence that while such viruses evolve adaptations to their host’s immune system, they accumulate other mutations that make them less able to cause infections in other people.
However, Omicron appears to be more infectious than all previously known variants.
Mutation signature of mice
Researchers at the Chinese Academy of Sciences in Beijing have now found evidence that Omicron may have evolved its large collection of unusual mutations in mice.
They believe that an earlier variant, from the lineage known as B.1.1, jumped from a human into a mouse in mid-2020. Over time, it evolved a range of adaptations to its new host before causing an infection in another human in late 2021.
They identified 45 “point mutations” in the RNA of Omicron that they propose occurred after the variant split from its last known common ancestor in humans.
Past research suggests RNA viruses tend to pick up more mutations in particular bases, according to which animal host they are replicating inside.
Using this knowledge, the authors of the new paper have previously identified the mutation “signature” of different animal hosts of SARS-CoV-2.
Their new study found that the relative frequency of the new point mutations in Omicron is characteristic of evolution in a mouse host rather than a human host.
They discovered that the mutation signature of Omicron is different from several variants known to have evolved in humans, including three variants isolated from patients with chronic COVID-19.
The scientists also found that several mutations in Omicron’s spike protein, which SARS-CoV-2 uses to cause infection in host cells, help the virus bind more tightly to its target receptor in mice.
They have published their findings in the Journal of Genetics and Genomics.
In the paper, they conclude:
“Collectively, our results suggest that the progenitor of Omicron jumped from humans to mice, rapidly accumulated mutations conducive to infecting that host, then jumped back into humans, indicating an inter-species evolutionary trajectory for the Omicron outbreak.”
Wild mice or lab mice?
Biologist Matt Ridley, author of Viral: The Search for the Origin of COVID-19, responded to the study on Twitter:
“Looks like Omicron developed from a human variant in a mouse. The question is: what mice and where? House mice in homes? Or lab mice in labs?”
“We believe that Omicron likely evolved in a wild mouse population,” the senior author of the study, Wenfeng Qian, Ph.D., told Micro B Life.
He said that mutations in the spike protein of Omicron significantly overlapped with mutations in SARS-CoV-2 viruses that have adapted to a mouse host.
However, 18 out of a total of 25 mutations in the Omicron spike were not present in any of the SARS-CoV-2 viruses they studied that were adapted to lab mice.
In addition, he pointed out that Omicron appears to have diverged from the B.1.1 lineage, with which it shares seven mutations.
“It is implausible that a lab will use a B.1.1 variant for their mouse adaptation experiments,” he commented. Instead, he said they would most likely use a strain of SARS-CoV-2 that researchers sequenced at the start of the pandemic, known as Wuhan-Hu-1.
Evolutionary biologist Mike Worobey, Ph.D., of the University of Arizona in Tucson, said the most plausible theory remained that Omicron evolved in an immune-compromised patient with a protracted [SARS-CoV-2] infection.
“I think their approach is really interesting, but I still think it is more likely that the unusual array of mutations in Omicron occurred in a chronically human [with the infection],” he told MBL.
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