In all living forms, the organization of the genetic material must enable two universally fundamental functions: the elaboration of biological properties and their transmission. In spite of these inexorable commonalties, genomes have a bewildering variety of forms, with differences occurring not only among distant taxa but also, in many instances, between members of the opposite sex within species. The rapidly growing field of comparative genomics offers a powerful tool for unraveling the evolutionary pathways that led to these karyotypic differences. This new method of genetic analysis [Fridolfsson et al, Proc Nat Acad Sci USA 1998; 95: 8147-8152. (Ref. 1)] complements still valuable, traditional experimental approaches.