Evolutionary histories of Escherichia coli TFs. We classified characterized regulators as global regulators, neighbor regulators, or other regulators, and we also analyzed some putative (as yet uncharacterized) regulators. We classified these transcription factors (TFs) as native because the divergence of E. coli from Shewanella, as acquired by horizontal transfer after that divergence, as ORFan (indicating horizontal gene transfer [HGT] from an unknown source), or as duplications within the E. coli lineage. For the duplicated TFs, we examined whether they regulate the same genes as their duplicates. For the HGT regulators, we examined whether they were co-transferred with nearby genes and whether they underwent repeated HGT within γ-Proteobacteria.