Here we identify duplicated genes in five mammalian genomes and classify these duplicates based on the mechanisms by which they were generated. Retrotransposition accounts for at least half of all predicted duplicate genes in these genomes, with tandem and interspersed duplicates comprising the other half. Estimation of the evolutionary rates in each class revealed greater rate asymmetry between retrotransposed and interspersed segmental duplicate pairs than between tandem duplicates, suggesting that retrotransposed and interspersed segmental duplicates are diverging more quickly. In an attempt to understand the basis of this asymmetry we identified disruption of flanking DNA as an indicator of new duplicate fate. Loss of synteny accelerates the asymmetry of divergence of DNA-mediated duplicates duplicates. These findings suggest that the differential evolution of duplicate genes may be significantly influenced by changes in local genome architecture and synteny.