Rank orders and signed interactions in evolutionary biology

  1. Kristina Crona  Is a corresponding author
  1. American University, United States


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.

Data availability

All data generated or analyzed during this study are included in the manuscript and supporting files.

Article and author information

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)
  4. Version of Record published: February 4, 2020 (version 2)


© 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.


  • 1,302
    Page views
  • 136
  • 5

Article citation count generated by polling the highest count across the following sources: Crossref, PubMed Central, Scopus.

Download links

A two-part list of links to download the article, or parts of the article, in various formats.

Downloads (link to download the article as PDF)

Open citations (links to open the citations from this article in various online reference manager services)

Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)

  1. Kristina Crona
Rank orders and signed interactions in evolutionary biology
eLife 9:e51004.
  1. Further reading

Further reading

    1. Evolutionary Biology
    Paul C Sereno, Nathan Myhrvold ... Lauren L Conroy
    Research Article

    A predominantly fish-eating diet was envisioned for the sail-backed theropod dinosaur Spinosaurus aegyptiacus when its elongate jaws with subconical teeth were unearthed a century ago in Egypt. Recent discovery of the high-spined tail of that skeleton, however, led to a bolder conjecture that S. aegyptiacus was the first fully aquatic dinosaur. The ‘aquatic hypothesis’ posits that S. aegyptiacus was a slow quadruped on land but a capable pursuit predator in coastal waters, powered by an expanded tail. We test these functional claims with skeletal and flesh models of S. aegyptiacus. We assembled a CT-based skeletal reconstruction based on the fossils, to which we added internal air and muscle to create a posable flesh model. That model shows that on land S. aegyptiacus was bipedal and in deep water was an unstable, slow-surface swimmer (<1 m/s) too buoyant to dive. Living reptiles with similar spine-supported sails over trunk and tail are used for display rather than aquatic propulsion, and nearly all extant secondary swimmers have reduced limbs and fleshy tail flukes. New fossils also show that Spinosaurus ranged far inland. Two stages are clarified in the evolution of Spinosaurus, which is best understood as a semiaquatic bipedal ambush piscivore that frequented the margins of coastal and inland waterways.

    1. Computational and Systems Biology
    2. Evolutionary Biology
    Guillem Santamaria, Chen Liao ... Joao B Xavier
    Research Article Updated

    Microbes have disproportionate impacts on the macroscopic world. This is in part due to their ability to grow to large populations that collectively secrete massive amounts of secondary metabolites and alter their environment. Yet, the conditions favoring secondary metabolism despite the potential costs for primary metabolism remain unclear. Here we investigated the biosurfactants that the bacterium Pseudomonas aeruginosa makes and secretes to decrease the surface tension of surrounding liquid. Using a combination of genomics, metabolomics, transcriptomics, and mathematical modeling we show that the ability to make surfactants from glycerol varies inconsistently across the phylogenetic tree; instead, lineages that lost this ability are also worse at reducing the oxidative stress of primary metabolism on glycerol. Experiments with different carbon sources support a link with oxidative stress that explains the inconsistent distribution across the P. aeruginosa phylogeny and suggests a general principle: P. aeruginosa lineages produce surfactants if they can reduce the oxidative stress produced by primary metabolism and have excess resources, beyond their primary needs, to afford secondary metabolism. These results add a new layer to the regulation of a secondary metabolite unessential for primary metabolism but important to change physical properties of the environments surrounding bacterial populations.