would tax the metabolic capacity of the host cell and put the plasmid-bearing cell at a disadvantage compared to a plasmid-free counterpart. Plasmids con­trol their copy number primarily at the stage of replication initiation. The frequency with which initiation of replication of iteron-containing plasmids occurs is modu­lated in part by sequestration of the origin region in nucleoprotein complexes and intermolecular pairing of complexes on different plasmids, which is referred to as "handcuffing" (14,44).