Intracellular competition shapes plasmid population dynamics.

Abstract

From populations of multicellular organisms to selfish genetic elements, conflicts between levels of biological organization are central to evolution. Plasmids are extrachromosomal, self-replicating genetic elements that face selective pressures from their hosts but also compete within the host cell for replication resources. Although theory indicates that within-cell selection matters for plasmid evolution, experimental measurement of these dynamics has remained elusive. We measured within-cell fitness of competing <i>Escherichia coli</i> plasmids and characterized their drift and selective dynamics. We made synthetic plasmid dimers that can be split in a controlled way to create balanced competition, which we probed experimentally. Incompatible plasmids coexist for an extended time owing to methylation-based replication control. Moreover, less transcriptionally active plasmids display a within-cell advantage and fix preferentially, favoring gene loss. Critically, fixation depends nontrivially on the interplay between plasmid transcription and translation. Our results show that plasmid evolution is driven by within- and between-cell dynamics.