Evolution of mosaic operons by horizontal gene transfer and gene displacement in situ

Background: Shuffling and disruption of operons and horizontal gene transfer are major contributions to the new, dynamic view of prokaryotic evolution. Under the 'selfish operon' hypothesis, operons are viewed as mobile genetic entities that are constantly disseminated via horizontal gene transfer, although their retention could be favored by the advantage of coregulation of functionally linked genes. Here we apply comparative genomics and phylogenetic analysis to examine horizontal transfer of entire operons versus displacement of individual genes within operons by horizontally acquired orthologs and independent assembly of the same or similar operons from genes with different phylogenetic affinities. Results: Since a substantial number of operons have been identified experimentally in only a few model bacteria, evolutionarily conserved gene strings were analyzed as surrogates of operons. The phylogenetic affinities within these predicted operons were assessed first by sequence similarity analysis and then by phylogenetic analysis, including statistical tests of tree topology. Numerous cases of apparent horizontal transfer of entire operons were detected. However, it was shown that apparent horizontal transfer of individual genes or arrays of genes within operons is not uncommon either and results in xenologous gene displacement in situ, that is, displacement of an ancestral gene by a horizontally transferred ortholog from a taxonomically distant organism without change of the local gene organization. On rarer occasions, operons might have evolved via independent assembly, in part from horizontally acquired genes. Conclusions: The discovery of in situ gene displacement shows that combination of rampant horizontal gene transfer with selection for preservation of operon structure provides for events in prokaryotic evolution that, a priori, seem improbable. These findings also emphasize that not all aspects of operon evolution are selfish, with operon integrity maintained by purifying selection at the organism level.