title: The operonic location of auto-transcriptional repressors is highly conserved in bacteria.
abstract: Bacterial genes are commonly encoded in clusters, known as operons, which share transcriptional regulatory control and often encode functionally related proteins that take part in certain biological pathways. Operons that are coregulated are known to colocalize in the genome, suggesting that their spatial organization is under selection for efficient expression regulation. However, the internal order of genes within operons is believed to be poorly conserved, and hence expression requirements are claimed to be too weak to oppose gene rearrangements. In light of these opposing views, we set out to investigate whether the internal location of the regulatory genes within operons is under selection. Our analysis shows that transcription factors (TFs) are preferentially encoded as either first or last in their operons, in the two diverged model bacteria Escherichia coli and Bacillus subtilis. In a higher resolution, we find that TFs that repress transcription of the operon in which they are encoded (autorepressors), contribute most of this signal by specific preference of the first operon position. We show that this trend is strikingly conserved throughout highly diverged bacterial phyla. Moreover, these autorepressors regulate operons that carry out highly diverse biological functions. We propose a model according to which autorepressors are selected to be located first in their operons in order to optimize transcription regulation. Specifically, the first operon position helps autorepressors to minimize leaky transcription of the operon structural genes, thus minimizing energy waste. Our analysis provides statistically robust evidence for a paradigm of bacterial autorepressor preferential operonic location. Corroborated with our suggested model, an additional layer of operon expression control that is common throughout the bacterial domain is revealed.
authors.affiliation: Department of Cell Research and Immunology, George S. Wise Faculty of Life Sciences, Tel Aviv University, Ramat Aviv, Tel Aviv, Israel.
authors.forename: Nimrod D
authors.initials: ND
authors.lastname: Rubinstein
authors.forename: David
authors.initials: D
authors.lastname: Zeevi
authors.forename: Yaara
authors.initials: Y
authors.lastname: Oren
authors.forename: Gil
authors.initials: G
authors.lastname: Segal
authors.forename: Tal
authors.initials: T
authors.lastname: Pupko
mesh_terms: D001412:Bacillus subtilis / Q000235:genetics*; D001426:Bacterial Proteins / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004926:Escherichia coli / Q000235:genetics*; D029968:Escherichia coli Proteins / Q000235:genetics; D019143:Evolution, Molecular; D015964:Gene Expression Regulation, Bacterial; D009876:Operon; D050436:Regulatory Elements, Transcriptional / Q000235:genetics*; D012097:Repressor Proteins / Q000235:genetics; D012641:Selection, Genetic; D015398:Signal Transduction; D014157:Transcription Factors / Q000235:genetics; D014158:Transcription, Genetic
chemical_list: D001426:Bacterial Proteins; D004268:DNA-Binding Proteins; D029968:Escherichia coli Proteins; C080002:MarA protein, E coli; C080004:MarR protein, E coli; D012097:Repressor Proteins; D014157:Transcription Factors; C080003:multiple antibiotic resistance protein B