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 haplotype network also supports this notion (Fig. 2) . Usually, ancestral 231 haplotypes have a greater probability of being in the interior, have more mutational 232 connections, and are geographically more widely distributed. The H1 haplotype is at the 233 center of the network and is found in four countries and many places in China. In addition, a 234 large portion of haplotypes is directly connected to H1. Therefore, it is likely that H1 is the 235 ancestral haplotype. As 45% of H1 are found in Wuhan, this location is the most plausible 236 origin of the ongoing pandemic. The copyright holder for this preprint (which was not peer-reviewed) is . https://doi.org/10.1101/2020.04.12.038554 doi: bioRxiv preprint and pangolin_2019 have diverged at about 47% of synonymous sites and infect different 251 hosts, the idea that they share five out of six critical amino acids within RBD through 252 convergent evolution seems far-fetched. 253 We therefore hypothesize that, instead of convergent evolution, the similarity of RBD 254 between SARS-CoV-2 and pangolin_2019 was caused by an ancient inter-genomic The copyright holder for this preprint (which was not peer-reviewed) is . https://doi.org/10.1101/2020.04.12.038554 doi: bioRxiv preprint responses in host cells (41-45 [31 , 32-35] . During the SARS spread, frequency of several 300 orf8 mutations fluctuated in accordance with different phases of the outbreak, suggesting that 301 orf8 underwent adaptation during the SARS epidemic [24] . It is suggested that 84S may 302 induce structural disorder in the C-terminus of the protein and may generate a novel 303 phosphorylation target for Serine/Threonine kinases of the mammalian hosts [36] .