A large-scale effort to measure, detect and analyse protein-protein interactions 
using experimental methods is under way. These include biochemistry such as 
co-immunoprecipitation or crosslinking, molecular biology such as the two-hybrid 
system or phage display, and genetics such as unlinked noncomplementing mutant 
detection. Using the two-hybrid system, an international effort to analyse the 
complete yeast genome is in progress. Evidently, all these approaches are 
tedious, labour intensive and inaccurate. From a computational perspective, the 
question is how can we predict that two proteins interact from structure or 
sequence alone. Here we present a method that identifies gene-fusion events in 
complete genomes, solely based on sequence comparison. Because there must be 
selective pressure for certain genes to be fused over the course of evolution, 
we are able to predict functional associations of proteins. We show that 215 
genes or proteins in the complete genomes of Escherichia coli, Haemophilus 
influenzae and Methanococcus jannaschii are involved in 64 unique fusion events. 
The approach is general, and can be applied even to genes of unknown function.