A The substitution frequency for each site was analyzed based on S sequences retrieved from the GISAID database. B Distribution of 79 site mutations from the S protein. The site with a black frame means this mutation was selected based on comparative analysis of the viral genome derived from animal hosts. C The overall normalized transduction rates of all mutations across different cell cultures. The tiny cartoons shown in the figure represent species from different mammalian orders. The tissue origin of these cell cultures is shown on the x-axis. D A 3D structure of the S-ACE2 complex showing that del69-70, D80Y, S98F, T572I, and Q675H are located outside the RBD of the S proteins.