Nucleotide substitutions in the HA1 domain of seasonal influenza virus H3N2 occur in temporal clusters, which was interpreted as a result of recurrent selective sweeps underlying antigenic drift. However, classical theory by Watterson suggests that episodic substitutions are mainly due to stochastic genealogy combined with unique genetic structure of influenza virus: High mutation rate over a nonrecombining viral segment. This explains why even larger variance in the number of allelic fixations per year is observed in nonantigenic gene segments of H3N2 than in antigenic (hemagglutinin and neuraminidase) segments. Using simulation, we confirm that allelic substitutions at nonrecombining segments with high mutation rate become temporally clustered without selection. We conclude that temporal clustering of fixations, as it is primarily caused by inherent randomness in genealogical process at linked sites, cannot be used as an evidence of positive selection in the H3N2 population. This effect of linkage and highmutation rate should be carefully considered in analyzing the genomic patterns of allelic substitutions in asexually reproducing systems in general.
Bibliographical noteFunding Information:
This work was supported by a grant of the TEPIK (Transgovernmental Enterprise for Pandemic Influenza in Korea), which is a part of Korea Healthcare Technology R&D Project by Ministry of Health and Welfare, Republic of Korea (Grant No: A103001) and the Ewha Global Top5 Grant 2013 of Ewha Womans University to Y.K.
© The Author(s) 2014.
- Index of dispersion
- Influenza virus
- Positive selection