Horizontal gene transfer and the evolution of transcriptional regulation in Escherichia coli

Background: Most bacterial genes were acquired by horizontal gene transfer from other bacteria instead of being inherited by continuous vertical descent from an ancient ancestor. To understand how the regulation of these acquired genes evolved, we examined the evolutionary histories of transcription factors and of regulatory interactions from the model bacterium Escherichia coli K12. Results: Although most transcription factors have paralogs, these usually arose by horizontal gene transfer rather than by duplication within the E. coli lineage, as previously believed. In general, most neighbor regulators-regulators that are adjacent to genes that they regulate-were acquired by horizontal gene transfer, whereas most global regulators evolved vertically within the gamma-Proteobacteria. Neighbor regulators were often acquired together with the adjacent operon that they regulate, and so the proximity might be maintained by repeated transfers (like 'selfish operons'). Many of the as yet uncharacterized (putative) regulators have also been acquired together with adjacent genes, and so we predict that these are neighbor regulators as well. When we analyzed the histories of regulatory interactions, we found that the evolution of regulation by duplication was rare, and surprisingly, many of the regulatory interactions that are shared between paralogs result from convergent evolution. Another surprise was that horizontally transferred genes are more likely than other genes to be regulated by multiple regulators, and most of this complex regulation probably evolved after the transfer. Conclusion: Our findings highlight the rapid evolution of niche-specific gene regulation in bacteria.