The genomic and epidemiological dynamics of human influenza A virus

Nature. 2008 May 29;453(7195):615-9. doi: 10.1038/nature06945. Epub 2008 Apr 16.


The evolutionary interaction between influenza A virus and the human immune system, manifest as 'antigenic drift' of the viral haemagglutinin, is one of the best described patterns in molecular evolution. However, little is known about the genome-scale evolutionary dynamics of this pathogen. Similarly, how genomic processes relate to global influenza epidemiology, in which the A/H3N2 and A/H1N1 subtypes co-circulate, is poorly understood. Here through an analysis of 1,302 complete viral genomes sampled from temperate populations in both hemispheres, we show that the genomic evolution of influenza A virus is characterized by a complex interplay between frequent reassortment and periodic selective sweeps. The A/H3N2 and A/H1N1 subtypes exhibit different evolutionary dynamics, with diverse lineages circulating in A/H1N1, indicative of weaker antigenic drift. These results suggest a sink-source model of viral ecology in which new lineages are seeded from a persistent influenza reservoir, which we hypothesize to be located in the tropics, to sink populations in temperate regions.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, N.I.H., Intramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Evolution, Molecular*
  • Genetic Drift
  • Genetic Variation
  • Genome, Viral / genetics*
  • Hemagglutinin Glycoproteins, Influenza Virus / genetics
  • Humans
  • Influenza A Virus, H1N1 Subtype / genetics*
  • Influenza A Virus, H1N1 Subtype / immunology
  • Influenza A Virus, H3N2 Subtype / genetics*
  • Influenza A Virus, H3N2 Subtype / immunology
  • Influenza, Human / epidemiology*
  • Influenza, Human / virology*
  • Models, Biological
  • Neuraminidase / genetics
  • New York / epidemiology
  • New Zealand / epidemiology
  • Phylogeny
  • Reassortant Viruses / genetics
  • Reassortant Viruses / immunology


  • Hemagglutinin Glycoproteins, Influenza Virus
  • Neuraminidase