The genes encoding synapsin (Syn) and the tissue inhibitor of metalloproteinase (Timp) exhibit a nested organization that is conserved in fruit fly and vertebrates. Analysis of the human and Fugu genomes show that the evolution of Syn-Timp gene families is characterized by duplications, secondary loss and the partitioning of ancestral functions. Of particular interest are two duplicate Syn-Timp loci in Fugu that have accumulated complementary degenerate mutations such that each Syn duplicate produces one of the two transcripts generated from the single ancestral gene, and one of the Timp genes is lost.