Preprint Open Access
Over the past three years, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has repeatedly experienced 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 in which the mutations leading to the formation of the SARS-CoV-2 Omicron variants, we compared the sequences of 129 Omicron BA.1-related isolates, 141 BA.1.1-related isolates, and 122 BA.2-related isolates, and tried to dissolve the evolutionary processes of the SARS-CoV-2 Omicron variants, including the order of mutations leading to the formation of the SARS-CoV-2 Omicron variants and the occurrence of homologous recombination. As a result, we concluded that the formations of a part of Omicron isolates BA.1, BA.1.1, and BA.2 were not the products 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 we have shown here is that the Omicron variants are formed by an entirely new mechanism that cannot be explained by previous biology, and knowing the way how the SARS-CoV-2 variants were formed prompts a reconsideration of the SARS-CoV-2 pandemic.
Tanaka and Miyazawa Unnaturalness in the evolution process of SARS CoV-2.pdf