Synthetic sequence entanglement augments stability and containment of genetic information in cells

Overlapping genes for synthetic biology Overlapping genes yield multiple distinct proteins when translated in alternative reading frames of the same nucleotide sequence. Blazejewski et al. developed a computational algorithm to predict de novo sequence entanglement and experimentally generated functional synthetic overlapping genes. When a sequence of interest was co-encoded with an essential gene in a living bacterium, its evolutionary stability substantially increased. When a gene of interest was synthetically overlapped with a toxin gene, its horizontal gene transfer frequency between bacteria was strongly suppressed. This generalizable strategy for designing, building, and testing overlapping genes helps stabilize vertical gene evolution and restrict horizontal gene flow. Science , this issue p. 595