Previously, we presented evidence that it is possible to predict functional
coupling between genes based on conservation of gene clusters between geno
mes, With the rapid increase in the availability of prokaryotic sequence da
ta, it has become possible to verify. and apply the technique. In this pape
r, we extend our characterization of the parameters that determine the util
ity of the approach, and we generalize the approach in a way that supports
detection of common classes of functionally coupled genes (e.g., transport
and signal transduction clusters), Now that the analysis includes over 30 c
omplete or nearly complete genomes, it has become clear that this approach
will play a significant role in supporting efforts to assign functionality
to the remaining uncharacterized genes in sequenced genomes.