We describe a method for comparative macrorestriction mapping of the c
hromosomes of Escherichia coil strains. In this method, a series of ph
ysically tagged E. coli K-12 alleles serve as mobile landmarks for map
ping DNAs from other strains. This technique revealed evidence of stra
in-specific chromosomal additions or deletions in a pathogenic isolate
and can be applied to most strains, yielding information on genealogy
as well as virulence. In theory, the same strategy can be used to map
and compare genomic DNAs from a wide variety of species.