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Over the past three years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has repeatedly caused pandemics, generating various mutated variants ranging from Alpha to Omicron. In this study, we aimed to clarify the evolutionary processes leading to the formation of SARS-CoV-2 Omicron variants, focusing on Omicron variants with many amino acid mutations in the spike protein among SARS-CoV-2 isolates. To determine the order of mutations leading to the formation of the SARS-CoV-2 Omicron variants, we compared the sequences of 129 Omicron BA.1-related, 141 BA.1.1-related, and 122 BA.2-related isolates, and attempted to clarify the evolutionary processes of SARS-CoV-2 Omicron variants, including the order of mutations leading to their formation and the occurrence of homologous recombination. As a result, we concluded that the formation of a part of Omicron isolates BA.1, BA.1.1, and BA.2 was not the product of genome evolution, as is commonly observed in nature, such as the accumulation of mutations and homologous recombinations. Furthermore, the study of 35 recombinant isolates of Omicron variants BA.1 and BA.2 confirmed that Omicron variants were already present in 2020. The analysis showed that Omicron variants were formed by an entirely new mechanism that cannot be explained by previous biology, and knowing how the SARS-CoV-2 variants were formed prompts a reconsideration of the SARS-CoV-2 pandemic
SARS-CoV-2, evolution, Puerto RIco, Omicron BA.2, Omicron BA.1
SARS-CoV-2, evolution, Puerto RIco, Omicron BA.2, Omicron BA.1
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