RT Journal Article
T1 Recoding of synonymous genes to expand evolutionary landscapes requires control of secondary structure affecting translation
A1 Escudero García-Calderón, José Antonio
A1 Nivina, Aleksandra
A1 Cambray, Guillaume
A1 López Igual, Rocío
A1 Loot, Céline
A1 Mazel, Didier
AB Synthetic DNA design needs to harness the many information layers embedded in a DNA string. We previously developed the Evolutionary Landscape Painter (ELP), an algorithm that exploits the degeneracy of the code to increase protein evolvability. Here, we have used ELP to recode the integron integrase gene (intI1) in two alternative alleles. Although synonymous, both alleles yielded less IntI1 protein and were less active in recombination assays than intI1. We spliced the three alleles and mapped the activity decrease to the beginning of alternative sequences. Mfold predicted the presence of more stable secondary structures in the alternative genes. Using synonymous mutations, we decreased their stability and recovered full activity. Following a design-build-test approach, we have now updated ELP to consider such structures and provide streamlined alternative sequences. Our results support the possibility of modulating gene activity through the ad hoc design of 5′ secondary structures in synthetic genes.
PB Wiley
SN 1097-0290
YR 2017
FD 2017-09-12
LK https://hdl.handle.net/20.500.14352/19289
UL https://hdl.handle.net/20.500.14352/19289
LA eng
NO Unión Europea - FP7
NO Centro Nacional para la Investigación Científica (Francia)
NO Séptimo Programa Marco de la Unión Europea
NO Fondation pour la Recherche Médicale
NO Agencia Nacional de Investigación de Francia
NO Gobierno de Francia
NO Comunidad de Madrid
DS Docta Complutense
RD 31 dic 2025