Journal
ELIFE
Volume 6, Issue -, Pages -Publisher
ELIFE SCIENCES PUBLICATIONS LTD
DOI: 10.7554/elife.26875
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Funding
- National Institute of General Medical Sciences [R01GM102198]
- National Institute of Allergy and Infectious Diseases [R01A1127893]
- National Heart, Lung, and Blood Institute [R01HL081595, K24HL093294, K23HL091059]
- Howard Hughes Medical Institute Faculty Scholar Award
- Simons Foundation Faculty Scholar Award
- National Science Foundation [DGE-1256082]
- Hertz Foundation
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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.
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