As the Human Genome Project advances, it is clear that the emphasis will switch from accumulation of data to their interpretation. Comparative genomics provides a powerful way in which to analyse sequence data. Indeed, there is already a long list of 'model' organisms, which allow comparative analyses in a variety of ways. The very small vertebrate genome of the pufferfish provides a simple and economical way of comparing sequence data from mammals and fish, representing a large evolutionary divergence and so permitting the identification of essential elements that are still present in both species. These elements include genes and the associated machinery that controls their expression; elements that, in many cases, have survived the test of time.