Molecular Evolution of MERS Coronavirus: Dromedaries as a Recent Intermediate Host or Long-Time Animal Reservoir?

Lau, Susanna K. P.; Wong, Antonio C. P.; Lau, Terrence C. K.; Woo, Patrick C. Y.

The models of spike glycoprotein from each clade were built. It was observed that the amino acid substitutions observed by multiple alignments appeared to be randomly distributed throughout the structure (Figure 6 ). Based on the model, we did not observe specific evolutionary patterns of the MERS-CoV spike protein. However, intriguingly, the residue at position 1020 can distinguish between clade A and B (Figure 4 ). The glutamine (Q1020) and arginine residues (R1020) at that position are highly conserved in clade A and clade B, respectively, except for a histidine residue (H1020) found in 12 lineage B5 strains. Together with results from selective pressure analysis, this suggests that this amino acid residue may play a role during the molecular evolution of S protein of MERS-CoV and divergence of different lineages. 1224 and 1250 were also predicted to be positively selected sites among clade B strains by at least one method ( Table 2 ). In addition, codon 879 was predicted to be positively selected among clade A strains, whereas codons 312 and 1020 were predicted to be positively selected among clade B strains by at least one method (Table 2) . Furthermore, codons 1250 and 1020 were predicted to be positively selected among clade B3 and B5 strains, respectively, by MEME method (Table 2 ). However, none of these amino acid residues were within the receptor binding domain of MERS-CoV, suggesting that there has not been strong selective pressure at the receptor-binding interphase during virus evolution.