Omicron: a chimera of two early SARS-CoV-2 lineages (preprint)

ABSTRACT

The current global epidemiology of COVID-19 is now characterized by the emergence and rapid spread of the SARS-CoV-2 Omicron variant on a global scale 1,2 . Despite the variant’s prompt predominance, there remain knowledge gaps in its origin and evolution history 3–6 . Here, we show that Omicron lineage SARS-CoV-2 is characterized by the feature of chimera. It was generated by genomic recombination of two early PANGO lineages of SARS-CoV-2. In the recombination event, strains with medium or high circulating intensity like SARS-CoV-2/human/USA/COR-21-434196/2021 belonging to PANGO lineage BA.1 provided the fundamental genome and served as the major parents, while the rare lineage strains like SARS-CoV-2/human/IRN/Ir-3/2019 belonging to B.35, as the minor parents, hybridized their genomic fractions into the major genomes at position 21593-23118nt. This recombination event results in 22 amino acid residue substitutions for the variant of Omicron, including 16 in the pivotal RBD of the spike protein. These substitutions have led to some subtle variations in the spatial structure and the affinity to hACE2 receptor of the spike protein 7,8 , thereby raising concerns about the effectiveness of available vaccines and antibody therapeutics 9–12 . The global spread and explosive growth of the SARS-CoV-2 in human population increase opportunities for future recombination 13–15 .