Table 2. Selected statistically significant polymorphic sites and their potential function or structural insights.

Protein	Site	Residues	Effect	Location/Potential Effect
PB2	358	E, V	Residue only	Cap-binding domain (318-483 aa)37
	649	V, I	Residue only	Host-specific domain (538-678 aa)39
	199	A, T	Residue and host	Genomic marker between avian and human IAVs17
PB1-F2	75	H, L, R	Residue and host	Part of a positively charged subdomain required for the localization of full-length peptide to mitochondria18
PA	323	V, I	Host-residue interaction	Compensate for the variation at site 545 to stabilize the molecule
	545	I, V	Residue only	Compensate for the variation at site 323 to stabilize the molecule
	187	L, I	Residue and host	N-terminal endonuclease domain of PA (1-196 aa)50
HA	173	N, T	Residue and host	Sa antigenic site51
	203	N, S	Residue only	Sb antigenic site51
NS1	7	S, L, T	Residue only	dsRNA binding domain52
	27	I, M	Residue only	dsRNA binding domain52
	101*	D, E	Residue only	Interacts with the PI3K-inhibitory domain; might act as nuclear export signal and key residue for the NS1-CPSF30 interaction in H5N1 viruses53
	103*	F, Y	Residue only	Interacts with the PI3K-inhibitory domain, increase in IFN antagonism when tested in H5N1 background54
	118*	R, K	Residue only	Allows closer packing of the PI3K helix to the NS1 protein
	227	E, G	Residue and host	PDZ-binding motif; genomic marker between avian and human IAVs17
NEP	7	S, L, T	Residue only	protease-sensitive N-terminaldomain21; function unknown
	70	S, G	Residue and host	M1 binding domain21; genomic marker between avian and human IAVs17
	64*	K, T	Residue only	M1 binding domain21; increases the negative charge of the M1-binding domain
	86*	R, I	Residue only	M1 binding domain21; increases the negative charge of the M1-binding domain
	88*	K, T	Residue only	M1 binding domain21; increases the negative charge of the M1-binding domain

These positions were based on the sequences used in this study.

*The polymorphic sites with underlying allele effect.