1. Genetics and Genomics
  2. Microbiology and Infectious Disease
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Population genomics of intrapatient HIV-1 evolution

  1. Fabio Zanini
  2. Johanna Brodin
  3. Lina Thebo
  4. Christa Lanz
  5. Göran Bratt
  6. Jan Albert
  7. Richard A Neher  Is a corresponding author
  1. Max Planck Institute for Developmental Biology, Germany
  2. Karolinska Institute, Sweden
  3. Stockholm South General Hospital, Sweden
  4. Karolinska Institutet, Sweden
Research Article
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Cite this article as: eLife 2015;4:e11282 doi: 10.7554/eLife.11282

Abstract

Many microbial populations rapidly adapt to changing environments with multiple variants competing for survival. To quantify such complex evolutionary dynamics in vivo, time resolved and genome wide data including rare variants are essential. We performed whole-genome deep sequencing of HIV-1 populations in 9 untreated patients, with 6-12 longitudinal samples per patient spanning 5-8 years of infection. The data can be accessed and explored via an interactive web application. We show that patterns of minor diversity are reproducible between patients and mirror global HIV-1 diversity, suggesting a universal landscape of fitness costs that control diversity. Reversions towards the ancestral HIV-1 sequence are observed throughout infection and account for almost one third of all sequence changes. Reversion rates depend strongly on conservation. Frequent recombination limits linkage disequilibrium to about 100bp in most of the genome, but strong hitch-hiking due to short range linkage limits diversity.

Article and author information

Author details

  1. Fabio Zanini

    Evolutionary Dynamics and Biophysics, Max Planck Institute for Developmental Biology, Tübingen, Germany
    Competing interests
    No competing interests declared.
  2. Johanna Brodin

    Department of Microbiology Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  3. Lina Thebo

    Department of Microbiology, Tumor and Cell Biology, Karolinska Institute, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  4. Christa Lanz

    Evolutionary Dynamics and Biophysics, Max Planck Institute for Developmental Biology, Tübingen, Germany
    Competing interests
    No competing interests declared.
  5. Göran Bratt

    Department of Clinical Science and Education, Stockholm South General Hospital, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  6. Jan Albert

    Department of Microbiology, Tumor and Cell Biology, Karolinska Institutet, Stockholm, Sweden
    Competing interests
    No competing interests declared.
  7. Richard A Neher

    Evolutionary Dynamics and Biophysics, Max Planck Institute for Developmental Biology, Tübingen, Germany
    For correspondence
    richard.neher@tuebingen.mpg.de
    Competing interests
    Richard A Neher, Reviewing editor, eLife.

Ethics

Human subjects: The study was carried out according to the Declaration of Helsinki. Ethical approval was granted by the Regional Ethical Review board in Stockholm, Sweden (Dnr 2012/505-31/12). Patients participating in the study gave written and oral informed consent to participate.

Reviewing Editor

  1. Arup K Chakraborty, Massachusetts Institute of Technology, United States

Publication history

  1. Received: September 1, 2015
  2. Accepted: December 8, 2015
  3. Accepted Manuscript published: December 10, 2015 (version 1)
  4. Version of Record published: January 8, 2016 (version 2)

Copyright

© 2015, Zanini et al.

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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