1. Epidemiology and Global Health
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The effects of a deleterious mutation load on patterns of influenza A/H3N2's antigenic evolution in humans

  1. Katia Koelle  Is a corresponding author
  2. David A Rasmussen
  1. Duke University, United States
Research Article
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Cite this article as: eLife 2015;4:e07361 doi: 10.7554/eLife.07361


Recent phylogenetic analyses indicate that RNA virus populations carry a significant deleterious mutation load. This mutation load has the potential to shape patterns of adaptive evolution via genetic linkage to beneficial mutations. Here, we examine the effect of deleterious mutations on patterns of influenza A subtype H3N2's antigenic evolution in humans. By first analyzing simple models of influenza that incorporate a mutation load, we show that deleterious mutations, as expected, act to slow the virus's rate of antigenic evolution, while making it more punctuated in nature. These models further predict three distinct molecular pathways by which antigenic cluster transitions occur, and we find phylogenetic patterns consistent with each of these pathways in influenza virus sequences. Simulations of a more complex phylodynamic model further indicate that antigenic mutations act in concert with deleterious mutations to reproduce influenza's spindly hemagglutinin phylogeny, co-circulation of antigenic variants, and high annual attack rates.

Article and author information

Author details

  1. Katia Koelle

    Department of Biology, Duke University, Durham, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
  2. David A Rasmussen

    Department of Biology, Duke University, Durham, United States
    Competing interests
    The authors declare that no competing interests exist.

Reviewing Editor

  1. Arne Traulsen, MPI Ploen, Germany

Publication history

  1. Received: March 10, 2015
  2. Accepted: September 14, 2015
  3. Accepted Manuscript published: September 15, 2015 (version 1)
  4. Version of Record published: October 20, 2015 (version 2)


© 2015, Koelle & Rasmussen

This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.


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