The origin and underlying driving forces of the SARS-CoV-2 outbreak

Shu-Miaw Chaw; Jui-Hung Tai; Shi-Lun Chen; Chia-Hung Hsieh; Sui-Yuan Chang; Shiou-Hwei Yeh; Wei-Shiung Yang; Pei-Jer Chen; Hurng-Yi Wang

The skew of synonymous variants toward high frequency deserves further discussion, 126 as it relates to the underlying force driving the SARS-CoV-2 outbreak. The puzzle is 127 probably rooted in how high and low frequency mutations are inferred. The results shown in 128 the Fig. 1a are based on an outgroup comparison. The divergence at synonymous sites 129 between SARS-CoV-2 and RaTG13 is 17%, approximately 3-fold greater than between 130 humans and rhesus macaques [22] . With such high level of divergence, the possibility of 131 multiple substitutions cannot be ignored, especially since substitution in the coronavirus 132 genome is strongly biased toward transitions (see above). Indeed, among all non-singleton 133 mutations listed in Table 2 , 62% of the changes are C-T transitions.