Primary and promiscuous functions coexist during evolutionary innovation through whole protein domain acquisitions
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
Article and author information
Author details
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.
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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