BACKGROUND: Genome comparisons have revealed major lateral gene transfer between 
the three primary kingdoms of life - Bacteria, Archaea, and Eukarya. Another 
important evolutionary phenomenon involves the evolutionary mobility of protein 
domains that form versatile multidomain architectures. We were interested in 
investigating the possibility of a combination of these phenomena, with an 
invading gene merging with a pre-existing gene in the recipient genome.
RESULTS: Complete genomes of fifteen bacteria, four archaea and one eukaryote 
were searched for interkingdom gene fusions (IKFs); that is, genes coding for 
proteins that apparently consist of domains originating from different primary 
kingdoms. Phylogenetic analysis supported 37 cases of IKF, each of which 
includes a 'native' domain and a horizontally acquired 'alien' domain. IKFs 
could have evolved via lateral transfer of a gene coding for the alien domain 
(or a larger protein containing this domain) followed by recombination with a 
native gene. For several IKFs, this scenario is supported by the presence of a 
gene coding for a second, stand-alone version of the alien domain in the 
recipient genome. Among the genomes investigated, the greatest number of IKFs 
has been detected in Mycobacterium tuberculosis, where they are almost always 
accompanied by a stand-alone alien domain. For most of the IKF cases detected in 
other genomes, the stand-alone counterpart is missing.
CONCLUSIONS: The results of comparative genome analysis show that IKF formation 
is a real, but relatively rare, evolutionary phenomenon. We hypothesize that 
IKFs are formed primarily via the proposed two-stage mechanism, but other than 
in the Actinomycetes, in which IKF generation seems to be an active, ongoing 
process, most of the stand-alone intermediates have been eliminated, perhaps 
because of functional redundancy.