Time:  Tuesday, September 19, 11:00
Place: NCBI Library B2/38A

Punctuated Interpandemic Evolution of Influenza A Virus

Yuri I. Wolf (with Cecile Viboud, Edward C. Holmes, Eugene V. Koonin and 
David J. Lipman).

The interpandemic evolution of the influenza A virus hemagglutinin (HA) 
protein is commonly considered a paragon of rapid evolutionary change 
under positive selection in which amino acid replacements are fixed by 
virtue of their effect on antigenicity, enabling the virus to evade the 
immune system. We performed phylogenetic analyses of the recently 
obtained large and relatively unbiased samples of the HA sequences from 
1995-2005 isolates of the H3N2 and H1N1 subtypes of influenza A virus. 
Unexpectedly, it was found that the evolution of H3N2 HA was dominated 
by long intervals of neutral sequence evolution without substantial 
antigenic change ("stasis" periods) that are characterized by an excess 
of synonymous over nonsynonymous substitutions per site, lack of 
association of amino acid replacements with epitope regions, and slow 
extinction of coexisting virus lineages. These periods of stasis are 
punctuated by shorter intervals of rapid evolution under positive 
selection during which new dominant lineages quickly displace previously 
coexisting ones. The dominance of positive selection during intervals of 
rapid evolution is supported by the dramatic excess of amino acid 
replacements in the epitope regions of HA compared to replacements in 
the rest of the HA molecule. In contrast, the stasis intervals showed a 
much more uniform distribution of replacements over the HA molecule, 
with a statistically significant difference in the pattern of 
substitutions between the two modes of evolution.