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.

To assess adaptive evolution of MERS-CoV, dN/dS ratios (ω) in S gene across the 219 strains were calculated on codon-by-codon basis. The overall ω was 0.424737 (0.392404 and 0.439492 for clade A and B strains, respectively), with most codons having ω < 1, indicating purifying selection (Table 2) . Nevertheless, four codons were predicted to have ω > 1 by different methods with statistical significance, including codons 26 and 312 by fixed effects likelihood (FEL) method, codon 1250 by mixed-effects model of evolution (MEME) method, and codon 1224 by both FEL and MEME methods, indicating possible functional constraints at these positions during evolution. Among them, codons 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.