Canalization of the evolutionary trajectory of the human influenza virus
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RESEARCH ARTICLE
Open Access
Canalization of the evolutionary trajectory of the human influenza virus Trevor Bedford1,2,3*, Andrew Rambaut3,4 and Mercedes Pascual1,2
Abstract Background: Since its emergence in 1968, influenza A (H3N2) has evolved extensively in genotype and antigenic phenotype. However, despite strong pressure to evolve away from human immunity and to diversify in antigenic phenotype, H3N2 influenza shows paradoxically limited genetic and antigenic diversity present at any one time. Here, we propose a simple model of antigenic evolution in the influenza virus that accounts for this apparent discrepancy. Results: In this model, antigenic phenotype is represented by a N-dimensional vector, and virus mutations perturb phenotype within this continuous Euclidean space. We implement this model in a large-scale individual-based simulation, and in doing so, we find a remarkable correspondence between model behavior and observed influenza dynamics. This model displays rapid evolution but low standing diversity and simultaneously accounts for the epidemiological, genetic, antigenic, and geographical patterns displayed by the virus. We find that evolution away from existing human immunity results in rapid population turnover in the influenza virus and that this population turnover occurs primarily along a single antigenic axis. Conclusions: Selective dynamics induce a canalized evolutionary trajectory, in which the evolutionary fate of the influenza population is surprisingly repeatable. In the model, the influenza population shows a 1- to 2-year timescale of repeatability, suggesting a window in which evolutionary dynamics could be, in theory, predictable.
Background Epidemic influenza is responsible for between 250,000 and 500,000 global deaths annually, with influenza A (and in particular, A/H3N2) having caused the bulk of human mortality and morbidity [1]. Influenza A (H3N2) has continually circulated within the human population since its introduction in 1968, exhibiting recurrent seasonal epidemics in temperate regions and less periodic transmission in the tropics. During this time, H3N2 influenza has continually evolved both genetically and antigenically. Most antigenic drift is thought to be driven by changes to epitopes in the hemagglutinin (HA) protein [2]. Phylogenetic analysis of the relationships among HA sequences has revealed a distinctive genealogical tree showing a single predominant trunk lineage and side branches that persist for only 1 to 5 years before going extinct [3]. This tree shape is indicative of * Correspondence: [email protected] 1 Department of Ecology and Evolutionary Biology, University of Michigan, Ann Arbor, MI, 48109, USA Full list of author information is available at the end of the article
serial replacement of strains over time; H3N2 influenza shows rapid evolution, but low standing genetic diversity. This observation has remained puzzling from an epidemiological standpoint. Antigenic evolution occurs rapidly, and strong diversifying selection exists to escape from
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