Transposon Tn21, flagship of the floating genome

The transposon Tn21 and a group of closely related transposons (the Tn21 fa mily) are involved in the global dissemination of antibiotic resistance det erminants in gram-negative facultative bacteria. The molecular basis for th eir involvement is carriage by the Tn21 family of a mobile DNA element (the integron) encoding a site-specific system for the acquisition of multiple antibiotic resistance genes. The paradigm example, Tn21, also carries genes for its own transposition and a mercury resistance (mer) operon. We have c ompiled the entire 19,671-bp sequence of Tn21 and assessed the possible ori gins and functions of the genes it contains. Our assessment adds molecular detail to previous models of the evolution of Tn21 and is consistent with t he insertion of the integron In2 into an ancestral Tn501-like mer transposo n. Codon usage analysis indicates distinct host origins for the ancestral m er operon, the integron, and the gene cassette and two insertion sequences which lie within the integron. The sole gene of unknown function in the int egron, orf5, resembles a puromycin-modifying enzyme from an antibiotic prod ucing bacterium. A possible seventh gene in the mer operon (merE), perhaps with a role in Hg(II) transport, lies in the junction between the integron and the mer operon. Analysis of the region interrupted by insertion of the integron suggests that the putative transposition regulator, tnpM, is the C -terminal vestige of a tyrosine kinase sensor present in the ancestral mer transposon. The extensive dissemination of the Tn21 family may have resulte d from the fortuitous association of a genetic element for accumulating mul tiple antibiotic resistances (the integron) with one conferring resistance to a toxic metal at a time when clinical, agricultural and industrial pract ices were rapidly increasing the exposure to both types of selective agents . The compendium offered here will provide a reference point for ongoing ob servations of related elements in multiply resistant strains emerging world wide.