The omicron variant of SARS-CoV-2 diverged from previous SARS-CoV-2 variants as a result of adaptive evolution, in which beneficial mutations are passed to future generations through natural selection, rather than through recombination between previous variants, according to a large international research team. The study, recently published in nature, is the first to describe the genomic profile of Omicron and examine the origins of the variant.
“We saw that SARS-CoV-2 generated three main variants – alpha, delta and omicron – in about 16 months, which is very surprising since other viruses do not make large evolutionary leaps as repeatedly,” said Maciej Boni, associate professor of the Biology, Penn State, who led the recombination analysis for this global collaboration. “The latest variant – Omicron – is exceptional because of the even bigger leap it has made in the evolution of its spike protein.”
Boni found that Omicron’s spike protein has more than 30 mutations compared to previous variants, many of which are known to affect host antibody neutralization.
“Given that Omicron has taken such a huge leap forward evolutionarily, we wanted to investigate why and how this might have happened,” he said.
To do this, the team – led by the Center for Epidemic Response and Innovation in South Africa – analyzed all 686 omicron sequences available as of December 7, 2021. They found that Omicron falls within the B.1.1 lineage, which also includes the Alpha variant. Interestingly, the team found that Omicron is genetically distinct from Alpha as well as all other known variants of interest.
“This means that while Omicron is in the same lineage as the Alpha variant, it has changed so much that it is largely unrecognizable as a cousin or nephew of the Alpha variant,” Boni said. “When the Omicron genome was first sequenced, it became clear that this virus had the potential to be phenotypically very different from previous SARS-CoV-2 variants with which we were familiar.”
To determine when the Omicron variant first appeared, the team used a technique called time-calibrated Bayesian phylogenetic analysis. They estimated that the date when the most recent common ancestor of all omicrons existed was early October 2021.
Next, the team applied a selection analysis to the 686 omicron sequences and found evidence of positive natural selection in many genes as the variant split from other B.1.1 lines. “This finding led to our conclusion that adaptive evolution played a significant role in the early emergence and establishment of omicron,” said Boni. “This finding suggests that Omicron is likely the result of an evolutionary process that produced a highly transmissible virus that partially eludes our antibody responses.”
In addition, the finding ruled out recombination of earlier variants in the origin of Omicron.
“We have not found convincing evidence that Omicron is a recombinant of previous SARS-CoV-2 variants,” Boni said.
The team found that some Omicron samples showed faint evidence of inheriting genetic material from a delta virus, but statistical analysis could not rule out chance or small sequencing errors as causes of this strange recombination signal.
“Given recent misinformation suggesting that the Omicron and Delta variants have recombined into a ‘Deltacron’ supervariant, it is important to note that such a recombination is indeed possible, but there is currently no evidence to support this.” said Boni. “Furthermore, if it does occur, there is no telling what properties such a virus would have in relation to, among other things, its ability to transmit and/or cause serious disease.”
Regarding the transmissibility of omicron, the team concluded that partial immune evasion was likely a key reason for the rapid spread of omicron in South Africa, given that the proportion of the South African population who were immune (either to infection, vaccination or both) , was over 60%. .
“This notion that omicron can partially escape the immune system is supported by other recent evidence showing an increased risk of SARS-CoV-2 reinfection associated with the appearance of omicron,” Boni said. “We also now know that Omicron’s viral load is higher in infected people, which also contributes significantly to its high transmission rate.”
Boni noted that the current Omicron wave is a reminder for all Americans to keep our COVID-19 vaccinations as up to date as possible.
“We cannot afford to endure another calendar year of half a million deaths,” he said.
Other institutions represented on paper are Lancet Laboratories, the Botswana Harvard HIV Reference Laboratory, the Harvard TH Chan School of Public Health, the Botswana Presidential COVID-19 Taskforce, the National Health Laboratory Service of South Africa, the University of KwaZulu-Natal, the University of the Witwatersrand, the University of Bern, the University of the Free State, Diagnofirm Medical Laboratories, the University of Edinburgh, the University of Pretoria, Emweb bv, the University of Cape Town, Stellenbosch University, Fundacao Oswaldo Cruz, the Universidade Federal de Minas Gerais, the NHLS Groote Schuur Laboratory, the Wellcome Center for Infectious Diseases Research in Africa, the Temple University, the University of Oxford, the Ministry of Health and Wellness of Botswana, the NHLS Port Elizabeth Laboratory, the Walter Sisulu University, the NHLS Tygerberg Laboratory, Charlotte Maxeke Johannesburg Academic Hospital, Botswana-Baylor Children’s Clinical Center of E xcellence, Baylor College of Medicine, Center for the AIDS Research Program in South Africa, the University of Botswana, PathCare Entertainment and the University of Washington.