1. Evolutionary Biology
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Contingency and chance erase necessity in the experimental evolution of ancestral proteins

  1. Victoria Cochran Xie
  2. Jinyue Pu  Is a corresponding author
  3. Brian PH Metzger
  4. Joseph W Thornton  Is a corresponding author
  5. Bryan C Dickinson  Is a corresponding author
  1. University of Chicago, United States
Research Article
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Cite this article as: eLife 2021;10:e67336 doi: 10.7554/eLife.67336

Abstract

The roles of chance, contingency, and necessity in evolution is unresolved, because they have never been assessed in a single system or on timescales relevant to historical evolution. We combined ancestral protein reconstruction and a new continuous evolution technology to mutate and select B-cell-lymphoma-2-family proteins to acquire protein-protein-interaction specificities that occurred during animal evolution. By replicating evolutionary trajectories from multiple ancestral proteins, we found that contingency generated over long historical timescales steadily erased necessity and overwhelmed chance as the primary cause of acquired sequence variation; trajectories launched from phylogenetically distant proteins yielded virtually no common mutations, even under strong and identical selection pressures. Chance arose because many sets of mutations could alter specificity at any timepoint; contingency arose because historical substitutions changed these sets. Our results suggest that patterns of variation in BCL-2 sequences – and likely other proteins, too – are idiosyncratic products of a particular, unpredictable course of historical events.

Data availability

The high throughput sequencing data of evolved BCL-2 family protein variants were deposited in the National Center for Biotechnology Information (NCBI) Sequence Read Archive (SRA) databases. They can be accessed via BioProject: PRJNA647218. The processed sequencing data are available on Dryad (https://doi.org/10.5061/dryad.866t1g1ns). The coding scripts and reference sequences for processing the data are available on Github (https://github.com/JoeThorntonLab/BCL2.ChanceAndContingency).

The following data sets were generated

Article and author information

Author details

  1. Victoria Cochran Xie

    Department of Chemistry, University of Chicago, Chicago, United States
    Competing interests
    No competing interests declared.
  2. Jinyue Pu

    Department of Chemistry, University of Chicago, Chicago, United States
    For correspondence
    pujy@uchicago.edu
    Competing interests
    Jinyue Pu, Has a patent on the proximity-dependent split RNAP technology used in this work (US Patent App. 16/305,298, 2020)..
  3. Brian PH Metzger

    Department of Ecology and Evolutionary Biology, University of Chicago, Chicago, United States
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-4878-2913
  4. Joseph W Thornton

    Department of Ecology and Evolution, University of Chicago, Chicago, United States
    For correspondence
    joet1@uchicago.edu
    Competing interests
    No competing interests declared.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-9589-6994
  5. Bryan C Dickinson

    Department of Chemistry, University of Chicago, Chicago, United States
    For correspondence
    Dickinson@uchicago.edu
    Competing interests
    Bryan C Dickinson, Has a patent on the proximity-dependent split RNAP technology used in this work (US Patent App. 16/305,298, 2020)..
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-9616-1911

Funding

National Institutes of Health (R01GM131128)

  • Joseph W Thornton

National Institutes of Health (R01GM121931)

  • Joseph W Thornton

National Institutes of Health (R01GM139007)

  • Joseph W Thornton

National Institutes of Health (F32GM122251)

  • Brian PH Metzger

National Science Foundation (DGE-1746045)

  • Victoria Cochran Xie

National Science Foundation (1749364)

  • Bryan C Dickinson

The content is solely the responsibility of the authors and the funders had no input on the study design, analysis, or conclusions.

Reviewing Editor

  1. Virginie Courtier-Orgogozo, Université Paris-Diderot CNRS, France

Publication history

  1. Received: February 8, 2021
  2. Accepted: May 30, 2021
  3. Accepted Manuscript published: June 1, 2021 (version 1)
  4. Version of Record published: July 15, 2021 (version 2)

Copyright

© 2021, Xie 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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