RT Journal Article
T1 Primary and promiscuous functions coexist during evolutionary innovation through whole protein domain acquisitions
A1 Escudero García-Calderón, José Antonio
A1 Nivina, Aleksandra
A1 Kemble, Harry E
A1 Loot, Céline
A1 Tenaillon, Olivier
A1 Mazel, Didier
AB 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.
PB eLife Sciences Publications,
SN 2050-084X
YR 2020
FD 2020-12-15
LK https://hdl.handle.net/20.500.14352/6867
UL https://hdl.handle.net/20.500.14352/6867
LA eng
NO Unión Europea. Horizonte 2020
NO Unión Europea. FP7
NO Ministerio de Ciencia e Innovación (MICINN)
NO Comunidad de Madrid
NO Centre National de la Recherche Scientifique
NO French National Research Agency
NO Fondation pour la Recherche Medicale
NO Paris Descartes University – Sorbonne Paris Cite´ , Fondation pour la Recherche Medicale
DS Docta Complutense
RD 13 abr 2025