1. Institute of Evolutionary Biology, University of Edinburgh, Ashworth Laboratories, Edinburgh EH9 3JT, UK
2. Department of Zoology, University of Oxford, South Parks Road, Oxford OX1 3PS, UK
3. Center for Infectious Disease Dynamics, Department of Biology, The Pennsylvania State University, Mueller Laboratory, University Park, Pennsylvania 16802, USA
4. Fogarty International Center, National Institutes of Health, Bethesda, Maryland 20892, USA
5. Laboratory of Infectious Diseases, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA

Correspondence to: Andrew Rambaut¹Edward C. Holmes^3,4 Correspondence and requests for materials should be addressed to A.R. (Email: a.rambaut@ed.ac.uk) and E.C.H. (Email: ech15@psu.edu).

Abstract

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.