key: cord-0713491-tjczejbu authors: Yeh, T.-Y.; Contreras, G. P. title: Tajima D test accurately forecasts Omicron / COVID-19 outbreak date: 2021-12-02 journal: nan DOI: 10.1101/2021.12.02.21267185 sha: 30d0c2441ce4eb2b03ec0ba99fac7cf30cc0de95 doc_id: 713491 cord_uid: tjczejbu On 26 November 2021, the World Health Organization designated the SARS-CoV-2 variant B.1.1.529, Omicron, a variant of concern. However, the phylogenetic and evolutionary dynamics of this variant remain unclear. An analysis of the 131 Omicron variant sequences from November 9 to November 28, 2021 reveals that variants have diverged into at least 6 major subgroups. 86.3% of the cases have an insertion at amino acid 214 (INS214EPE) of the spike protein. Neutrality analysis of DH (-2.814, p<0.001) and Zeng E (0.0583, p=1.0) tests suggested that directional selection was the major driving force of Omicron variant evolution. The synonymous (Dsyn) and nonsynonymous (Dnonsyn) polymorphisms of the Omicron variant spike gene were estimated with Tajima D statistic to eliminate homogenous effects. Both D ratio (Dnonsyn/Dsyn, 1.57) and DD (Dsyn-Dnonsyn, 0.63) indicate that purifying selection operates at present. The low nucleotide diversity (0.00008) and Tajima D value (-2.709, p<0.001) also confirms that Omicron variants had already spread in human population for more than the 6 weeks than has been reported. These results, along with our previous analysis of Delta and Lambda variants, also supports the validity of the Tajima D test score, with a threshold value as -2.50, as an accurate predictor of new COVID-19 outbreaks. where a1 is defined as (Tajima, 1989 , Hughes, et al., 2005 . Dsyn was 105 defined as kS − S*S, divided by the standard error of that difference, and Dnonsyn was 106 defined as kN − S*N, divided by the standard error of that difference (Tajima, 1989 , 107 Hughes, et al., 2005 . 108 109 Results and Discussion 110 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted December 2, 2021. ; https://doi.org/10.1101/2021.12.02.21267185 doi: medRxiv preprint The insertion mutation Ins214EPE at the spike protein is present in some 112 The phylogenetic tree identifies at least 6 major subgroups CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted December 2, 2021. ; https://doi.org/10.1101/2021.12.02.21267185 doi: medRxiv preprint We have previously used neutrality tests to analyze the selection pressure of SARS-135 CoV-2 in the shipboard quarantine on the Diamond Princess (Yeh and Contreras, 136 2021a) and the influence of full vaccination coverage on Delta variants among 137 different countries (Yeh and Contreras, 2021b) . We also proposed that Tajima (Table 1) , and strong selection and/or demographic expansion was 154 operating in Omicron. 155 . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted December 2, 2021. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted December 2, 2021. CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted December 2, 2021. ; https://doi.org/10.1101/2021.12.02.21267185 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. The copyright holder for this preprint this version posted December 2, 2021. ; https://doi.org/10.1101/2021.12.02.21267185 doi: medRxiv preprint . CC-BY-NC-ND 4.0 International license It is made available under a is the author/funder, who has granted medRxiv a license to display the preprint in perpetuity. (which was not certified by peer review) The copyright holder for this preprint this version posted December 2, 2021. ; https://doi.org/10.1101/2021.12.02.21267185 doi: medRxiv preprint Statistical method for testing the neutral mutation hypothesis by 274 DNA polymorphism Update on Omicron Emerging viral mutants in Australia suggest RNA 278 recombination event in the SARS-CoV-2 genome Viral transmission and evolution dynamics of SARS-CoV-2 in shipboard quarantine Full vaccination is imperative to suppress SARS