Skip to main content
bioRxiv
  • Home
  • About
  • Submit
  • ALERTS / RSS
Advanced Search
New Results

The mutation rates and mutational bias of influenza A virus

Matthew D. Pauly, Megan Procario, View ORCID ProfileAdam S. Lauring
doi: https://doi.org/10.1101/110197
Matthew D. Pauly
1Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Megan Procario
1Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
Adam S. Lauring
1Department of Microbiology and Immunology, University of Michigan, Ann Arbor, MI 48109
2Division of Infectious Diseases, Department of Internal Medicine, University of Michigan, Ann Arbor, MI 48109
  • Find this author on Google Scholar
  • Find this author on PubMed
  • Search for this author on this site
  • ORCID record for Adam S. Lauring
  • For correspondence: alauring@med.umich.edu
  • Abstract
  • Full Text
  • Info/History
  • Metrics
  • Supplementary material
  • Preview PDF
Loading

Abstract

Influenza virus has a high mutation rate, and this low replicative fidelity contributes to its capacity for rapid evolution. Clonal sequencing and fluctuation tests have suggested that the mutation rate of influenza A virus is 7.1 × 10−6 − 4.5 × 10−5 substitutions per nucleotide per cell infection cycle and 2.7 × 10−6 − 3.0 × 10−5 substitutions per nucleotide per strand copied (s/n/r). However, sequencing assays are biased toward mutations with minimal impacts on viral fitness and fluctuation tests typically investigate only a subset of the twelve mutational classes. We developed a fluctuation test based on reversion to fluorescence in a set of virally encoded mutant green fluorescent proteins. This method allowed us to measure the rates of selectively neutral mutations representative of all 12 mutational classes in the context of an unstructured RNA. We measured an overall mutation rate of 1.8 × 10−4 s/n/r for PR8 (H1N1) and 2.5 × 10−4 s/n/r for Hong Kong 2014 (H3N2). The replication mode was linear. The mutation rates of these divergent strains are significantly higher than previous estimates and suggest that each replicated genome will have an average of 2-3 mutations. The viral mutational spectrum is heavily biased toward A to G and U to C transitions, resulting in a transition to transversion bias of 2.7 and 3.6 for the two strains. These mutation rates were relatively constant over a range of physiological temperatures. Our high-resolution analysis of influenza virus mutation rates will enable more refined models of its molecular evolution.

Significance The rapid evolution of influenza virus is a major problem in public health. A key factor driving this rapid evolution is the virus’ very high mutation rate. We developed a new method for measuring the rates of all 12 mutational classes in influenza virus, which eliminates some of the biases of existing assays. We find that the influenza virus mutation rate is much higher than previously reported and is consistent across two distinct strains and a range of temperatures. Our data suggest that influenza viruses replicate at their maximally tolerable mutation rates, highlighting both the virus’ evolutionary potential and its significant constraints.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
Back to top
PreviousNext
Posted February 21, 2017.
Download PDF

Supplementary Material

Email

Thank you for your interest in spreading the word about bioRxiv.

NOTE: Your email address is requested solely to identify you as the sender of this article.

Enter multiple addresses on separate lines or separate them with commas.
The mutation rates and mutational bias of influenza A virus
(Your Name) has forwarded a page to you from bioRxiv
(Your Name) thought you would like to see this page from the bioRxiv website.
CAPTCHA
This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Share
The mutation rates and mutational bias of influenza A virus
Matthew D. Pauly, Megan Procario, Adam S. Lauring
bioRxiv 110197; doi: https://doi.org/10.1101/110197
Reddit logo Twitter logo Facebook logo LinkedIn logo Mendeley logo
Citation Tools
The mutation rates and mutational bias of influenza A virus
Matthew D. Pauly, Megan Procario, Adam S. Lauring
bioRxiv 110197; doi: https://doi.org/10.1101/110197

Citation Manager Formats

  • BibTeX
  • Bookends
  • EasyBib
  • EndNote (tagged)
  • EndNote 8 (xml)
  • Medlars
  • Mendeley
  • Papers
  • RefWorks Tagged
  • Ref Manager
  • RIS
  • Zotero
  • Tweet Widget
  • Facebook Like
  • Google Plus One

Subject Area

  • Microbiology
Subject Areas
All Articles
  • Animal Behavior and Cognition (4672)
  • Biochemistry (10337)
  • Bioengineering (7655)
  • Bioinformatics (26286)
  • Biophysics (13497)
  • Cancer Biology (10666)
  • Cell Biology (15408)
  • Clinical Trials (138)
  • Developmental Biology (8485)
  • Ecology (12803)
  • Epidemiology (2067)
  • Evolutionary Biology (16822)
  • Genetics (11381)
  • Genomics (15462)
  • Immunology (10596)
  • Microbiology (25165)
  • Molecular Biology (10198)
  • Neuroscience (54382)
  • Paleontology (399)
  • Pathology (1665)
  • Pharmacology and Toxicology (2889)
  • Physiology (4333)
  • Plant Biology (9234)
  • Scientific Communication and Education (1585)
  • Synthetic Biology (2554)
  • Systems Biology (6770)
  • Zoology (1461)