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

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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  1. Fabio Zanini
  2. Johanna Brodin
  3. Lina Thebo
  4. Christa Lanz
  5. Göran Bratt
  6. Jan Albert
  7. Richard A Neher
(2015)
Population genomics of intrapatient HIV-1 evolution
eLife 4:e11282.
https://doi.org/10.7554/eLife.11282
  1. Further reading

Further reading

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    Methods: Genetic variants associated with smoking initiation and alcohol consumption at the genome-wide significance level were selected as instrumental variables. Genetic associations with 24 gastrointestinal diseases were obtained from the UK Biobank, FinnGen study, and other large consortia. Univariable and multivariable MR analyses were conducted to estimate the overall and independent MR associations after mutual adjustment for genetic liability to smoking and alcohol consumption.

    Results: Genetic predisposition to smoking initiation was associated with increased risk of 20 of 24 gastrointestinal diseases, including 7 upper gastrointestinal diseases (gastroesophageal reflux, esophageal cancer, gastric ulcer, duodenal ulcer, acute gastritis, chronic gastritis and gastric cancer), 4 lower gastrointestinal diseases (irritable bowel syndrome, diverticular disease, Crohn's disease and ulcerative colitis), 8 hepatobiliary and pancreatic diseases (non-alcoholic fatty liver disease, alcoholic liver disease, cirrhosis, liver cancer, cholecystitis, cholelithiasis, acute and chronic pancreatitis), and acute appendicitis. Fifteen out of 21 associations persisted after adjusting for genetically-predicted alcohol consumption. Genetically-predicted higher alcohol consumption was associated with increased risk of duodenal cancer, alcoholic liver disease, cirrhosis, and chronic pancreatitis; however, the association for duodenal ulcer did not remain after adjustment for genetic predisposition to smoking initiation.

    Conclusion: This study provides MR evidence supporting causal associations of smoking with a broad range of gastrointestinal diseases, whereas alcohol consumption was associated with only a few gastrointestinal diseases.

    Funding: The Natural Science Fund for Distinguished Young Scholars of Zhejiang Province; National Natural Science Foundation of China; Key Project of Research and Development Plan of Hunan Province; the Swedish Heart Lung Foundation; the Swedish Research Council; the Swedish Cancer Society.