1. Evolutionary Biology
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Coupling adaptive molecular evolution to phylodynamics using fitness-dependent birth-death models

  1. David A Rasmussen  Is a corresponding author
  2. Tanja Stadler
  1. North Carolina State University, United States
  2. ETH Zurich, Switzerland
Research Article
  • Cited 4
  • Views 1,348
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Cite this article as: eLife 2019;8:e45562 doi: 10.7554/eLife.45562

Abstract

Beneficial and deleterious mutations cause the fitness of lineages to vary across a phylogeny and thereby shape its branching structure. While standard phylogenetic models do not allow mutations to feedback and shape trees, birth-death models can account for this feedback by letting the fitness of lineages depend on their type. To date, these multi-type birth-death models have only been applied to cases where a lineage's fitness is determined by a single character state. We extend these models to track sequence evolution at multiple sites. This approach remains computationally tractable by tracking the genotype and fitness of lineages probabilistically in an approximate manner. Although approximate, we show that we can accurately estimate the fitness of lineages and site-specific mutational fitness effects from phylogenies. We apply this approach to estimate the population-level fitness effects of mutations in Ebola and influenza virus, and compare our estimates with in vitro fitness measurements for these mutations.

Article and author information

Author details

  1. David A Rasmussen

    Department of Entomology and Plant Pathology, North Carolina State University, Raleigh, 27607, United States
    For correspondence
    drasmus@ncsu.edu
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9457-7561
  2. Tanja Stadler

    Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland
    Competing interests
    The authors declare that no competing interests exist.

Funding

Seventh Framework Programme (European Research Commission)

  • Tanja Stadler

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.

Reviewing Editor

  1. Aleksandra M Walczak, École Normale Supérieure, France

Publication history

  1. Received: January 27, 2019
  2. Accepted: July 26, 2019
  3. Accepted Manuscript published: August 14, 2019 (version 1)
  4. Accepted Manuscript updated: August 15, 2019 (version 2)
  5. Version of Record published: August 29, 2019 (version 3)

Copyright

© 2019, Rasmussen & Stadler

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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