[Study on the detection of positive selected codons on HA1 sequence of human influenza A subtype H3N2].
OBJECTIVE
To elucidate the evolution pattern of human influenza virus A H3 subtype by detecting positive selected codons in hemagglutinin gene.


METHODS
All H3 sequences in NCBI GenBank and influenza sequence database were downloaded and two step cluster method was applied to divide sequences into six groups, which were corresponding to different period by turns. Fixed Effect Model was applied to detect positive selected codons in each group, and two step cluster method was then used again to summarize variation patterns of selective pressure among sites.


RESULTS
Positive selected codons were different in groups corresponding different periods. 50 amino acid codons had been identified as positive selected sites in at least one time span. Among them, 42 codons belonged to one of the five known antigen-combinng regions. A larger amount of sites as well as relatively higher selection pressure were identified in antibody combining regions A and B. Results showed that the 50 sites could be divided into seven different patterns. While other six patterns corresponding to positive selected codons at only one time span, the sites of the seventh pattern were under positive selection in several periods.


CONCLUSIONS
Positive selection codons in evolution of H3A1 strains were alternated in different time period whereas antibody combining regions A and B played more important roles in the evolution process. Other 8 identified codons out of the antibody combining regions might belong to unknown antigen regions.
Xu
Hui-lin
HL
Department of Health Statistics and Social Medicine, School of Public Health, Fudan University, Shanghai 200032, China.
Zhang
Wen-tong
WT
Zhao
Nai-qing
NQ
Jiang
Qing-wu
QW
D000595:Amino Acid Sequence; D003062:Codon; D006388:Hemagglutinins / Q000235:genetics*; D006801:Humans; D053122:Influenza A Virus, H3N2 Subtype / Q000235:genetics*; D007251:Influenza, Human / Q000235:genetics*; D012641:Selection, Genetic
D003062:Codon; D006388:Hemagglutinins