Taming wild replicons: evolution and domestication of large extrachromosomal replicons

Bacterial genomes often contain extrachromosomal replicons (ERs), ranging from small, mobile plasmids to large, stably inherited elements, such as megaplasmids, secondary chromosomes, or chromids. Multipartite genomes, which include large ERs, are present in approximately 10% of sequenced bacterial species and are thought to have evolved as adaptive solutions to diverse ecological niches. Understanding how these replicons become essential genome components is critical for characterizing bacterial adaptability and genome plasticity. Large ERs become established within the host genome through evolutionary processes that shape their genetic content, promote the acquisition of core functions, and synchronize their replication and segregation with the bacterial cell cycle. In this review, we examine the origin, classification, and functional roles of large ERs. We highlight shared maintenance principles, such as dosage-dependent gene organization, replication control via methylation or checkpoint mechanisms, and dedicated partitioning systems or shared segregation machinery. Examples from Vibrio cholerae and Agrobacterium tumefaciens illustrate these mechanisms, and a conceptual model for ER domestication is proposed.