Primary and promiscuous functions coexist during evolutionary innovation through whole protein domain acquisitions
Investigation published in eLife
December 15th, 2020
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- toward 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 toward innovation
Escudero JA., Nivina A., Kemble HE., Loot C., Tenaillon O. and Mazel D.
 | Bacterial Genome Plasticity (BGP). Department of Genomes and Genetics. Institut Pasteur. |
 | Centre National de la Recherche Scientifique (CNRS). |
 | Departamento de Sanidad Animal. Facultad de Veterinaria. Universidad Complutense (UCM). |
| Servicio de Zoonosis de Transmisión Alimentaria y Resistencia a Antimicrobianos (ZTA). Centro de Vigilancia Sanitaria Veterinaria (VISAVET). Universidad Complutense (UCM). |
 | Université Sorbonne Paris Descartes. |
 | Université Paris Diderot. |
 | Institut national de la santé et de la recherche médicale (INSERM). |
