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Title: Orthologous transcription factors in bacteria have differentfunctions and regulate different genes

Journal Article · · PLoS Computational Biology

Transcription factors (TFs) form large paralogous genefamilies and have complex evolutionary histories. Here, we ask whetherputative orthologs of TFs, from bidirectional best BLAST hits (BBHs), areevolutionary orthologs with conserved functions. We show that BBHs of TFsfrom distantly related bacteria are usually not evolutionary orthologs.Furthermore, the false orthologs usually respond to different signals andregulate distinct pathways, while the few BBHs that are evolutionaryorthologs do have conserved functions. To test the conservation ofregulatory interactions, we analyze expression patterns. We find thatregulatory relationships between TFs and their regulated genes areusually not conserved for BBHs in Escherichia coli K12 and Bacillussubtilis. Even in the much more closely related bacteria Vibrio choleraeand Shewanella oneidensis MR-1, predicting regulation from E. coli BBHshas high error rates. Using gene-regulon correlations, we identify geneswhose expression pattern differs between E. coli and S. oneidensis. Usingliterature searches and sequence analysis, we show that these changes inexpression patterns reflect changes ingene regulation, even forevolutionary orthologs. We conclude that the evolution of bacterialregulation should be analyzed with phylogenetic trees, rather than BBHs,and that bacterial regulatory networks evolve more rapidly thanpreviously thought.

Research Organization:
Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States)
Sponsoring Organization:
USDOE Director. Office of Science. Biological andEnvironmental Research
DOE Contract Number:
DE-AC02-05CH11231
OSTI ID:
932521
Report Number(s):
LBNL-63466; R&D Project: VGTLAA; BnR: KP1102010; TRN: US200813%%96
Journal Information:
PLoS Computational Biology, Vol. 3, Issue 9; Related Information: Journal Publication Date: September2007
Country of Publication:
United States
Language:
English