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

José Antonio Escudero | Aleksandra Nivina | Harry E Kemble | Céline Loot | Olivier Tenaillon | Didier Mazel
eLife | 2020

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- toward single-strand-DNA recombination through the acquisition of the I2 α-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 toward innovation.

Pubmed ID: 33319743

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Associated grants

  • Agency: Centre National de la Recherche Scientifique, International
    Id: CNRS-UMR3525
  • Agency: Ministerio de Ciencia, Innovacion y Universidades de Espana, International
    Id: BIO2017-85056-P
  • Agency: Fondation pour la Recherche Médicale, International
    Id: FDT20150532465
  • Agency: EU-MSC Actions, International
    Id: PIEF-GA-2011-303022
  • Agency: EU FP7 HEALTH, International
    Id: 282004
  • Agency: EU-FP7 FET, International
    Id: 612146
  • Agency: Fondation pour la Recherche Médicale, International
    Id: DBF20160635736
  • Agency: Agence Nationale de la Recherche, International
    Id: ANR-10-LABX-62-IBEID
  • Agency: Agence Nationale de la Recherche, International
    Id: ANR-12- 897 BLAN-DynamINT
  • Agency: Comunidad de Madrid, International
    Id: 2016-T1/BIO-1105
  • Agency: H2020 Marie Skłodowska-Curie Actions, International
    Id: PIEF-GA-2011-303022
  • Agency: European Research Council, International
    Id: StG-803375
  • Agency: Ministerio de Ciencia e Innovación, International
    Id: BIO2017-85056-P
  • Agency: Fondation pour la Recherche Médicale, International
    Id: EQU201903007848
  • Agency: European Union 7th Framework Programme, International
    Id: 310944
  • Agency: Pierre and Marie Curie University, International
    Id: FP-7-PEOPLE2011-IEF
  • Agency: Pierre and Marie Curie University, International
    Id: ICADIGE

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