Primary and promiscuous functions coexist during evolutionary innovation through whole protein domain acquisitions

  1. José Antonio Escudero
  2. Aleksandra Nivina
  3. Harry E Kemble
  4. Céline Loot
  5. Olivier Tenaillon
  6. Didier Mazel  Is a corresponding author
  1. Institut Pasteur, France
  2. INSERM, France
  3. French National Institute of Health and Medical Research, INSERM, France

Abstract

Molecular examples of evolutionary innovation are scarce and generally involve point mutations. Innovation can occur through larger rearrangements, but here experimental data is extremely limited. Integron integrases innovated from double-strand- towards single-strand-DNA recombination through the acquisition of the I2 a-helix. To investigate how this transition was possible, we have evolved integrase IntI1 to what should correspond to an early innovation state by selecting for its ancestral activity. Using synonymous alleles to enlarge sequence space exploration, we have retrieved 13 mutations affecting both I2 and the multimerization domains of IntI1. We circumvented epistasis constraints among them using a combinatorial library that revealed their individual and collective fitness effects. We obtained up to 104-fold increases in ancestral activity with various asymmetrical trade-offs in single-strand-DNA recombination. We show that high levels of primary and promiscuous functions could have initially coexisted following I2 acquisition, paving the way for a gradual evolution towards innovation.

Data availability

Sequencing data has been deposited in Dryad under accession code doi:10.5061/dryad.zcrjdfn7x

The following data sets were generated

Article and author information

Author details

  1. José Antonio Escudero

    Genomes and Genetics, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-8552-2956
  2. Aleksandra Nivina

    Genomes and Genetics, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-1802-3724
  3. Harry E Kemble

    IAME, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0003-1480-5873
  4. Céline Loot

    Genomes and Genetics, Institut Pasteur, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
  5. Olivier Tenaillon

    French National Institute of Health and Medical Research, INSERM, Paris, France
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0002-3796-1601
  6. Didier Mazel

    Genomes and Genetics, Institut Pasteur, Paris, France
    For correspondence
    mazel@pasteur.fr
    Competing interests
    The authors declare that no competing interests exist.
    ORCID icon "This ORCID iD identifies the author of this article:" 0000-0001-6482-6002

Funding

Centre National de la Recherche Scientifique (CNRS-UMR3525)

  • Didier Mazel

Ministerio de Ciencia, Innovacion y Universidades de Espana (BIO2017-85056-P)

  • José Antonio Escudero

Fondation pour la Recherche Médicale (FDT20150532465)

  • Aleksandra Nivina

EU-MSC Actions (PIEF-GA-2011-303022)

  • José Antonio Escudero

EU FP7 HEALTH (282004)

  • Didier Mazel

EU-FP7 FET (612146)

  • Didier Mazel

Fondation pour la Recherche Médicale (DBF20160635736)

  • Didier Mazel

Agence Nationale de la Recherche (ANR-10-LABX-62-IBEID)

  • Didier Mazel

Agence Nationale de la Recherche (ANR-12- 897 BLAN-DynamINT)

  • Céline Loot

European Research Council (StG-803375)

  • José Antonio Escudero

Comunidad de Madrid (2016-T1/BIO-1105)

  • José Antonio Escudero

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

Reviewing Editor

  1. Paul B Rainey, Max Planck Institute for Evolutionary Biology, Germany

Publication history

  1. Received: April 20, 2020
  2. Accepted: December 14, 2020
  3. Accepted Manuscript published: December 15, 2020 (version 1)
  4. Version of Record published: January 7, 2021 (version 2)

Copyright

© 2020, Escudero 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. José Antonio Escudero
  2. Aleksandra Nivina
  3. Harry E Kemble
  4. Céline Loot
  5. Olivier Tenaillon
  6. Didier Mazel
(2020)
Primary and promiscuous functions coexist during evolutionary innovation through whole protein domain acquisitions
eLife 9:e58061.
https://doi.org/10.7554/eLife.58061
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