Essential Gene Acquisition Destabilizes Plasmid Inheritance

Extra-chromosomal genetic elements are important drivers of evolutionary transformations and ecological adaptations in prokaryotes with their evolutionary success often depending on their 'utility' to the host. Examples are plasmids encoding antibiotic resistance genes, which are known to proliferate in the presence of antibiotics. Plasmids carrying an essential host function are recognized as permanent residents in their host. Essential plasmids have been reported in several taxa where they often encode essential metabolic functions; nonetheless, their evolution remains poorly understood. Here we show that essential genes are rarely encoded on plasmids; evolving essential plasmids in Escherichia coli we further find that acquisition of an essential chromosomal gene by a plasmid can lead to plasmid extinction. A comparative genomics analysis of Escherichia isolates reveals few plasmid-encoded essential genes, yet these are often integrated into plasmid-related functions; an example is the GroEL/GroES chaperonin. Experimental evolution of a chaperonin-encoding plasmid shows that the acquisition of an essential gene reduces plasmid fitness regardless of the stability of plasmid inheritance. Our results suggest that essential plasmid emergence leads to a dose effect caused by gene redundancy. The detrimental effect of essential gene acquisition on plasmid inheritance constitutes a barrier for plasmid-mediated lateral gene transfer and supplies a mechanistic understanding for the rarity of essential genes in extra-chromosomal genetic elements.Author summary Mobile genetic elements have been extensively studied due to their role as agents of genetic innovation and rapid adaptation in prokaryotes. Specifically, prokaryotic plasmids have been the focus of investigation in the context of bacterial survival under growth limiting conditions with the prime example of resistance to antibiotics and heavy metals. In contrast, plasmids that encode for functions that are essential to their host viability are rarely described. We investigate the evolution of plasmids that encode for genes previously identified as essential for bacterial life. Our analysis of Escherichia isolates reveals only few plasmid-encoded essential genes, which likely function in the plasmid rather than the host life cycle. Following the evolution of plasmids encoding an essential gene in Escherichia coli in real time, we further find that the acquisition of a chromosomal essential gene may lead to plasmid loss. Our study supplies data and a mechanistic understanding on the rarity of essential genes in mobile genetic elements. We conclude that prokaryotic plasmids are rarely essential for their bacterial host.