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It has been emphasized that the phylogenetic tree for the HA1 of H3N2 isolates has a distinct, "ladder-like" shape, with a prominent trunk (the path from the root to the base of the latest included cluster of isolates) and, typically, short side branches .
This study supported earlier findings of positive selection for those amino acid positions involved in receptor and antibody binding and, more specifically, for a subset of 18 amino acid sites in HA1. found that 9 of these 18 positions showed evidence of positive selection only in the internal branches and not the terminal branches (i.e.
The observations of extremely rapid evolution of influenza A, especially in the HA gene, has led to the suggestion that the evolution of the surface regions of the HA is driven by continual positive selection.
In particular, Ratner et al., in a phylogenetic analysis of human H3 subtype HA genes, found a significantly higher rate of amino acid replacements than silent changes in antigenic positions of the HA1 domain (which consists of the N-terminal 329 residues of HA and includes the epitopes recognized by the immune system) as compared to the same rates (or rate ratios) for the C-terminal HA2 domain .
However, the temporal ordering of the Sydney isolates (1997–2002) is somewhat indistinct, with, for example, the dominant isolates of 2001 being derived from 1998 isolates rather than the dominant isolates of 2000 or 1999.
Associated with this is a major branching of the PA tree with one subtree comprised of isolates primarily from 2001–2003 and another subtree with isolates from 19–2005.
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 immune surveillance.
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.
Thus, the ascendancy of H1N1 in some seasons is, most likely, caused by the drop in the relative fitness of the previously prevailing H3N2 lineages as the fraction of susceptible hosts decreases during the stasis intervals.
The Influenza Genome Sequencing Project, funded and managed by the US National Institute of Allergy and Infectious Diseases, has recently generated over 1000 fully sequenced influenza genomes from clinical isolates obtained between 19 and publicly available in Genbank .