Table 1.

The entropy, information gain, and co-mutated positions of 15 amino acid positions on HA sequences

Position-epitope	Entropy	IG	Number of co-mutate positions	Co-mutated positions	Positive selection	Cluster Transition
145-A1	0.87	1.00	12	9,31,63,78,83,126,137,160,193,197,242,278	+ 2	+ 3
137-A	0.68	0.41	23	9,31,53,54,62,63,83,126,143,145,146,158,160,164,174,189,193,201,213,217,244,260,278		+
193-B	0.86	0.23	17	9,31,63,78,83,126,137,145,158,160,164,174,201,217,242,260,278	+	+
160-B	0.58	0.28	16	2,31,54,62,126,137,143,146,156,158,164,197,217,244,260,278		+
156-B	0.80	0.43	8	54,62,143,146,160,197,244,260	+	+
226-D	1.00	0.15	2	145,189	+
135-A	0.83	0.07	1	165	+
121-D	0.72	0.00	0		+
142-A	0.47	0.00	0		+
186-B	0.41	0.00	0		+
164-B	0.24	0.46	6	126,137,158,174,201,217,		+
201-D	0.27	0.36	4	137,164,174,217		+
78-E	0.14	0.29	4	31,63,126,242
174-D	0.32	0.47	4	137,164,201,217		+
63-E	0.19	0.39	6	78,83,126,137,242,278

¹ The epitope of the position on HA sequence.

² the position is under positive selection defined by Bush et al. [3].

³ the position is a cluster-difference substitution defined by Smith et al. [6].