Nature reveals where did the new crown Omicron variant come from?

More than two months after the Omicron variant of the coronavirus SARS-CoV-2 was first identified in South Africa, its spread around the world has been eye-popping
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Scientists have tracked it in more than 120 countries, but remain perplexed by a key question: Where did Omicron come from? The question of Omicron's origin is not just an academically important one
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Canadian vaccine and virologist Angela Rasmussen said the presence of such a highly transmissible variant may help scientists understand the risk of new variants and recommend measures to minimize them
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The World Health Organization's recently established Scientific Advisory Group on the Origin of Novel Pathogens (SAGO) met in January to discuss the origin of Omicron
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According to Marietjie Venter, a medical virologist at the University of Pretoria in South Africa, the group is expected to publish a report in early February
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Prior to this report, scientists were working on three theories: (1) Although researchers have sequenced millions of SARS-CoV-2 genomes, they may have simply missed a series of events that ultimately lead to Omicron Mutation; (2) Alternatively, the mutation may evolve a mutation in a person as part of a long-term infection; (3) it may arise in other animal hosts, such as mice or rats
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For now, whatever ideas researchers tend to lean toward, "it tends to come down to intuition rather than any kind of principled argument," says Richard Neher, a computational biologist at the University of Basel in Switzerland
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said Jinal Bhiman, a medical scientist at the National Institute of Infectious Diseases in Johannesburg, South Africa.

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"Everyone has their favorite hypothesis
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" The wildest genome researchers agree that Omicron is a recent arrival
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First discovered in South Africa and Botswana in early November 2021
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Retrospective testing has since identified early samples from individuals in the UK on 1 and 3 November, and from South Africa, Nigeria and the United States on 2 November
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Analysis of mutation rates in hundreds of sequenced genomes, and how quickly the virus spread through the population through December, put the date of its emergence around the end of September or early October of last year
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In southern Africa, Omicron may have spread from the dense urban Gauteng province between Johannesburg and Pretoria to other provinces and neighbouring Botswana
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But since Johannesburg is home to the continent's largest airport, this variant could have appeared anywhere in the world
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What sets Omicron apart is its remarkable number of mutations
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Compared with the original SARS-CoV-2 virus isolated in Wuhan, China, the variant has more than 50 mutations, about 30 of which lead to amino acid changes in the spike protein, which the coronavirus uses to attach and fuse with cells
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Whereas previously focused variants had no more than 10 such spike mutations
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Researchers have seen many of these mutations before
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Some were previously known to enhance the virus's ability to bind to the ACE2 receptor protein, or help it evade the body's immune system
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Omicron forms stronger binding capacity on ACE2 than previously seen variants
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It's also better at evading "neutralizing" antibodies produced by being vaccinated or infected with earlier variants
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Other changes to the spike protein appear to alter the way Omicron enters cells: it appears to be less adept at fusing directly with the cell membrane, preferring instead to enter cells after engulfing endosomes, lipid-enclosed air bubbles
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Another intriguing feature of Omicron is that, from a genomic point of view, it consists of three distinct sub-lineages: BA.
1, BA.
2 and BA.
3, and that Omicron has evolved over time is also constantly evolving
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Stealth Spread As SARS-CoV-2 replicates and spreads from person to person, random changes in its RNA sequence occur, some of which persist
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Massive coronavirus genomes also have the potential to undergo massive recombination, allowing viruses to evolve more quickly when there is selective pressure because mutations are more likely to persist if they make the virus more capable of multiplying under certain environmental conditions
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Although researchers have submitted nearly 7.
5 million SARS-CoV-2 sequences to the GISAID genome database, hundreds of millions of viral genomes from COVID-19 patients worldwide have yet to be sequenced
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South Africa, with about 28,000 genomes, has sequenced less than 1% of its known COVID-19 cases, and many nearby countries, from Tanzania to Zimbabwe and Mozambique, have submitted fewer than 1,000 sequences to GISAID
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Since some of the mutations in Omicron have not been seen before, this variation may have evolved in an environment that did not involve chains of transmission between humans
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Even in the broader group of sarbecoviruses, some changes in Omicron did not match any of the observed changes
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Another way chronic infection has evolved at a fast pace is chronic infection
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In chronically infected people, the virus can multiply for weeks or months, and different types of mutations can emerge to evade the body's immune system
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Chronic infection gives the virus "a chance to play cat and mouse with the immune system"
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Such chronic infections have been observed in people with compromised immune systems who cannot easily escape SARS-CoV-2
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For example, a December 2020 case report described a 45-year-old man with persistent infection
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Over the course of nearly five months in its host, SARS-CoV-2 accumulated nearly a dozen amino acid changes in its spike protein
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Some researchers think alpha appears in a chronically infected person because, like Omicron, it appears to accumulate changes at an accelerated rate
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"Viruses have to change to stay the course," says interdisciplinary virologist Ben Murrel at Karolinska Institutet
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Further complicating the situation, Omicron's properties may arise from combinations of mutations
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For example, two mutations found in Omicron -- N501Y along with Q498R -- increased one variant's ability to bind to the ACE2 protein by nearly 20-fold
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Mouse or rat SARS-CoV-2 is a promiscuous virus: it has spread to other animals
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The cell-based study found that, unlike earlier variants, Omicron's spike protein can bind to the ACE2 protein in turkey, chicken and mice
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One study found that the mutated N501Y–Q498R combination allowed the variant to bind tightly to rat ACE2
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According to a study of 45 mutations in Omicron, the patterns of single-nucleotide substitutions observed in Omicron's genome also appear to mirror those typically observed when coronaviruses evolve in mice, and are consistent with those observed in adaptation Switch mismatch observed in human coronaviruses
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The study noted that in human hosts, G-to-U substitutions tend to occur at a higher rate in RNA viruses than C-to-A switches, but Omicron did not exhibit this pattern
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It's possible, then, that SARS-CoV-2 acquired the mutation that made it a rat -- jumping from a sick person to a rat, possibly via contaminated sewage -- and then spread and evolved into Omicron in that animal population
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Infected rats may then come into contact with humans, triggering the emergence of Omicron
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The three sublineages of Omicron are sufficiently different that, according to this theory, each sublineage would represent a separate jump from animals to humans
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The darkest hour But also experts say it's a rare event for even a single virus to jump from an animal to a person -- let alone three
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Although some mutations in Omicron have been observed in rodents, that doesn't mean they don't occur or don't occur in humans as well, and are simply missed
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When SARS-CoV-2 spread to mink and deer, it did pick up changes, but not as many mutations as Omicron had accumulated, says evolutionary virologist Spyros Lytras of the University of Glasgow in the UK
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This means that there is insufficient evidence to suggest that Omicron's ex underwent rapid selection after finding a new home in the wild
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Many scientists say they may never discover the source of Omicron
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Omicron really shows us the humility it takes to think about our ability to understand the evolution of a virus like SARS-CoV-2
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References: https://