1. Evolutionary Biology
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Rank orders and signed interactions in evolutionary biology

  1. Kristina Crona  Is a corresponding author
  1. American University, United States
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Cite this article as: eLife 2020;9:e51004 doi: 10.7554/eLife.51004


Rank orders have been studied in evolutionary biology for almost a hundred years. Constraints on the order in which mutations accumulate are known from cancer drug treatment, and order constraints for species invasions are important in ecology. However, current theory on rank orders in biology is somewhat fragmented. Here we show how our previous work on inferring genetic interactions from comparative fitness data (Crona et al., 2017) is related to an influential approach to rank orders based on sign epistasis. Our approach depends on order perturbations that indicate interactions. We apply our results to malaria parasites and find that order perturbations beyond sign epistasis are prevalent for the antimalarial drug resistance landscape. This finding agrees with the observation that reversed evolution back to the ancestral type is difficult. Another application concerns bacteria adapting to a methanol environment.

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Author details

  1. Kristina Crona

    Mathematics and Statistics, American University, Washington DC, United States
    For correspondence
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1819-474X


No external funding was received for this work

Reviewing Editor

  1. Joachim Krug, University of Cologne, Germany

Publication history

  1. Received: August 14, 2019
  2. Accepted: January 5, 2020
  3. Accepted Manuscript published: January 14, 2020 (version 1)


© 2020, Crona

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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