RT Journal Article T1 Multicopy plasmids allow bacteria to escape from fitness trade-offs during evolutionary innovation A1 Escudero García-Calderón, José Antonio A1 Rodríguez-Beltrán, Jerónimo A1 Hernández-Beltrán, J. Carlos R. A1 De la Fuente, Javier A1 Fuentes-Hernández, Ayari A1 MacLean, R. Craig A1 Peña-Miller, Rafael A1 San Millan, Álvaro AB Understanding the mechanisms governing innovation is a central element of evolutionary theory. Novel traits usually arise through mutations in existing genes, but trade-offs between new and ancestral protein functions are pervasive and constrain the evolution of innovation. Classical models posit that evolutionary innovation circumvents the constraints imposed by trade-offs through genetic amplifications, which provide functional redundancy. Bacterial multicopy plasmids provide a paradigmatic example of genetic amplification, yet their role in evolutionary innovation remains largely unexplored. Here, we reconstructed the evolution of a new trait encoded in a multicopy plasmid using TEM-1 β-lactamase as a model system. Through a combination of theory and experimentation, we show that multicopy plasmids promote the coexistence of ancestral and novel traits for dozens of generations, allowing bacteria to escape the evolutionary constraints imposed by trade-offs. Our results suggest that multicopy plasmids are excellent platforms for evolutionary innovation, contributing to explain their extreme abundance in bacteria. SN 2397-334X YR 2018 FD 2018-04-09 LK https://hdl.handle.net/20.500.14352/94237 UL https://hdl.handle.net/20.500.14352/94237 LA eng NO Instituto de Salud Carlos III (CP15-00012, PI16-00860, MS15/00012) NO CIBER (CB06/02/0053) NO Fondo Europeo de Desarrollo Regional (FEDER) NO Royal Society (NA140196) NO UNAM-PAPIIT (IA201017, IA201016) NO Wellcome Trust NO Comunidad de Madrid (2016-T1/BIO-1105) NO Fondo Social Europeo (FSE) DS Docta Complutense RD 6 jul 2025