Parallel evolution of influenza across multiple spatiotemporal scales

Elife. 2017 Jun 27;6:e26875. doi: 10.7554/eLife.26875.

Abstract

Viral variants that arise in the global influenza population begin as de novo mutations in single infected hosts, but the evolutionary dynamics that transform within-host variation to global genetic diversity are poorly understood. Here, we demonstrate that influenza evolution within infected humans recapitulates many evolutionary dynamics observed at the global scale. We deep-sequence longitudinal samples from four immunocompromised patients with long-term H3N2 influenza infections. We find parallel evolution across three scales: within individual patients, in different patients in our study, and in the global influenza population. In hemagglutinin, a small set of mutations arises independently in multiple patients. These same mutations emerge repeatedly within single patients and compete with one another, providing a vivid clinical example of clonal interference. Many of these recurrent within-host mutations also reach a high global frequency in the decade following the patient infections. Our results demonstrate surprising concordance in evolutionary dynamics across multiple spatiotemporal scales.

Keywords: antigenic evolution; clonal interference; deep sequencing; epidemiology; evolutionary biology; genomics; hemagglutinin; human; infectious disease; influenza; microbiology; virus.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Evolution, Molecular*
  • Female
  • Genetic Variation*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Immunocompromised Host
  • Influenza A Virus, H3N2 Subtype / classification*
  • Influenza A Virus, H3N2 Subtype / genetics*
  • Influenza, Human / virology*
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Mutation
  • RNA, Viral / genetics
  • Sequence Analysis, DNA
  • Spatio-Temporal Analysis

Substances

  • RNA, Viral