The genome of each organism contains the potential to evolve novel functions that will allow it to thrive in alternative environments. There is not yet a sufficient understanding of the selective constraints on that potential to permit us to predict which genes are most likely to evolve a particular novel function or to predict the mutations that are most likely to lead to that function. Technological advances in the areas of rapid and massive DNA sequencing and in vitro evolution by sexual PCR (DNA shuffling) now make it possible to make an effective start on developing theory that will allow us to assess the evolutionary potential that is present in existing genomes.