FIG. 2.

Differentials of selective pressures on sites associated with amantadine resistance. (a) Differentials of selective pressures on sites associated with amantadine resistance between hosts. Selective pressures for human viruses are higher than for the viruses of other hosts at positions 26 and 31. Significantly higher selective pressures for human viruses were found only when compared to avian viruses at position 26 and only when compared to canine/equine viruses at position 27. The significant differences were observed only by eFEL. No significant differences were found by iFEL. The dN/dS ratios at positions 26 and 30 for canine/equine influenza virus could not be calculated because both the denominator and the numerator were zero. The dN/dS ratios at positions 27 and 31 for canine/equine influenza viruses are zero, as only the numerators were zero. *, significant differences were found by eFEL (P < 0.05). (b) Differentials of selective pressures on sites associated with amantadine resistance in human influenza virus by time. The dN/dS ratios for positions 26, 27, and 30 have become larger since 1966 (the introduction of amantadine) and 2000 (the beginning of the recent surge of amantadine-resistant strains), though there are no significant differences. In contrast, the dN/dS ratio for position 31 became smaller rather than larger. “inf” means infinity, as the denominator was zero. The dN/dS ratios at position 26 before 1965, at position 30 before 1965, and at position 30 before 1999 were zero, as only the numerators were zero. No significant differences were found by either eFEL or iFEL.