Evolutionary analyses of European H1N2 swine influenza A virus by placing timestamps on the multiple reassortment events

A novel H1N2 swine influenza A virus emerged in Europe since 1994. Previous phylogenetic analyses revealed that its genome segments were derived from H1N1 human virus, H3N2 human virus and avian-like H1N1/H3N2 swine virus, indicating the possibility of multiple reassortments events. However, dates of these reassortment events have not been investigated systematically. In this study, we used both global and local molecular clock concepts in a maximum likelihood framework to extrapolate the times of origins of the genome segments in European H1N2 swine viruses, and deduced that novel neuraminidase, hemagglutinin and other internal protein genes were introduced to the European H1N2 lineage at the 1970s, early 1980s and late 1980s, respectively through reassortments. Furthermore, in light of the evolutionary timescale reconstructed for the H1N2 viruses, we argue that further reassortments, in addition to those responsible for the introductions of novel genome segments, might have also occurred among the viruses prior to the outbreaks arose in United Kingdom at 1994. Our results confirm that the viral genes of various origins have stably maintained in swine population for many years before the multiple genetic reassortant was detected. Our evolutionary analyses also suggested that the HA and NA genes evolved in a significantly higher rate of synonymous substitutions after they were introduced from human to swine and established the European H1N2 swine lineage. (C) 2007 Elsevier B.V. All rights reserved.