A simple, fast, and biologically inspired computational approach for inferring genome-scale rearrangement phylogeny and ancestral gene order has been developed. This has been applied to eight Drosophila genomes. Existing techniques are either limited to a few hundred markers or a small number of taxa. This analysis uses over 14,000 genomic loci and employs discrete elements consisting of pairs of homologous genetic elements. The results provide insight into evolutionary chromosomal dynamics and synteny analysis, and inform speciation studies.