A computational study of bacterial gene regulation and adaptation ...

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Introductionfor which comes from the classic study by Jacob and Monod which demonstrated that the lacoperon and its repressor gene lacI are located adjacent to one another on the E. colichromosome. More recent research, described below, has expanded this to a genome-widescale.Using transcriptional regulatory network data for E. coli and Bacillus subtilis, two groupsshowed that a majority of TF genes are encoded close to their respective target genes in thechromosome (Hershberg et al. 2005; Janga et al. 2009; Menchaca-Mendez et al. 2005). Since,in prokaryotes, transcription and translation are coupled, this will ensure that the TF protein isproduced close to the gene itself, thus enhancing its ability to detect its target promoternearby. That co-localisation on the chromosome accelerates the search was also demonstratedusing biophysical simulations (Kolesov et al. 2007). In fact, a single-molecule study of LacIin live E. coli cells showed that the repressor spends 90% of search time moving along theDNA with little 3D diffusion (Elf et al. 2007). If this tendency for co-localisation isinfluenced by coupled transcription and translation, then such a trend should not be observedin eukaryotes; this was shown to be the case in the yeast S. cerevisiae (Hershberg et al. 2005).It is important to note however, that increasing the concentration of TFs would, in any case,improve search efficiency (Kolesov et al. 2007). However, many TFs have only a few bindingsites on the bacterial chromosome and therefore, are expressed in only a few copies. Thus,chromosomal co-localisation is the ideal mechanism for ensuring efficient binding sitesearching. However, one may expect this to be impractical for global TFs, which have manybinding sites, which invariably will be positioned over a large portion of the genome (Janga etal. 2009). In such cases, the observed high expression levels of the TFs involved will counterbalancethe negative effect of dispersed binding sites on search efficiency.Thus, in bacteria, the architecture of the transcriptional regulatory network imposesimmediate constraints on the positioning of genes in the chromosome. Though localisation ofTF genes and their targets on the eukaryotic chromosome is clearly non-random (Janga et al.2008), these influences are mechanistically less likely to be direct.16
I.4.5. Signal sensing in transcriptional regulationTranscription factors are particularly essential in order to ensure that the cell expresses theright genes under the influence of specific signals. As pointed out earlier, there is an intimateconnection between signals and TFs in bacteria. This is exceptionally well-characterised inparticular systems, the repressor of the lac operon and that of the trp operon for example. Aseries of recent works has taken advantage of the wealth of experimental informationavailable for E. coli in order to understand various patterns of interactions between signalsensing and transcriptional output.In the first study of its kind, more than 100 TFs in E. coli were classified into external,internal and hybrid, depending on the source of the signal to which they respond (Martinez-Antonio et al. 2006). External TFs respond to molecules that are transported into the cell fromthe environment, or via two-component signal transduction pathways where the sensingkinase is located on the cell membrane. Internal TFs sense molecules that are exclusivelyproduced by enzymes, or of cellular structures such as DNA supercoiling. Hybrid TFs sensemolecules such as amino acids which can be produced by the cell as well as transported intothe medium if available.Internal TFs control the largest number of target genes. On the other hand, external TFsgenerally achieve more specific regulation. Possibly as a consequence of this differentialdistribution of target specificity between internal and external TFs, FFLs were found tocontain a combination of internal and external sensing TFs (Janga et al. 2007b).Finally, proteins responsible for generating the signal (two-component sensors / transporters /enzymes) were found to co-localise with the downstream TF on the chromosome, particularlyif the TF belonged to the external sensing category (Janga et al. 2007a). Internal-sensing TFsrepresent the other end of the spectrum in this property. Though the interpretations offered forthe co-localisation of specific TFs and their target genes on the chromosome do not applyhere, other explanations are attractive: catabolic pathways can be horizontally acquired; sinceexternal metabolite sensing would in many cases respond to nutrients, such a genomicorganisation would allow efficient co-transfer of the nutrient sensors, TFs and the downstreamenzyme genes (Price et al. 2008).17
Page 3 and 4: Statement of lengthThis thesis does
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Chapter 2: Transcriptional control
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Chapter 4: Comparative genomics of
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two-domain architectures wherethese
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(A)60% of genomes from class4530150
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Discussion and conclusionsDiscussio
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Discussion and conclusionsD1.1.3. C
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Discussion and conclusionsD2. Futur
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BibliographyAmikam, D., Steinberger
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BibliographyBlattner, F.R., Plunket
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BibliographyChen, S.L., Hung, C.S.,
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BibliographyEchols, N., Harrison, P
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Bibliographysystem level analysis o
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BibliographyHerring, C.D., Raghunat
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BibliographyJenal, U., and Malone,
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BibliographyKeseler, I.M., Collado-
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BibliographyLee, S.H., Angelichio,
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BibliographyMcClelland, M., Sanders
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BibliographyO Croinin, T., Carroll,
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BibliographyPrice, M.N., Dehal, P.S
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BibliographySatriano, J., and Schlo
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BibliographySteinberger, O., Lapido
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BibliographyUssery, D.W., Wassenaar
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BibliographyYanofsky, C. 1981. Atte
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Appendix 1Appendix 1.1: Differences
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Appendix 1Appendix 1.5: Gene expres
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Appendix 2Appendix 2.1: Differences
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Appendix 2Appendix 2.3: Co-regulati
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Appendix 2Appendix 2.5: Flux coupli
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Appendix 2Appendix 2.7: Co-regulati
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Appendix 2Appendix 2.8B: Connectivi
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Appendix 2Appendix 2.10: Correlatio
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Appendix 2Appendix 2.12A: Robustnes
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Appendix 3Appendix 3Supplementary m
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Reaction ID Regulatory metabolite I
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Appendix 3Appendix 3.3B: Direct reg
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Appendix 3Appendix 3.4B: Direct reg
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Appendix 4Appendix 4Supplementary m
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Appendix 4Motile organisms are rich
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Appendix 4We can expand the analysi
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Appendix 5Appendix 5.1A: PFAMs for
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Appendix 5Appendix 5.1C: PFAMs for
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Appendix 5Appendix 5.2B: Small-mole
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Appendix 5Appendix 5.3: Organisms s
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Appendix 5Appendix 5.5: Partner dom
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Appendix 5fraction of SDRRs would a
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Appendix 5Appendix 5.6C: Non-hybrid
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Appendix 5Appendix 5.8: List of org
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Appendix 6Appendix 6List of genomes
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Appendix 648. Mycobacterium tubercu
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Appendix 6144. Bacillus cereus ATCC
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Appendix 6240. Nitrobacter winograd
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Appendix 6336. Cytophaga hutchinson
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Appendix 6432. Acinetobacter bauman
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Appendix 6528. Enterobacter sakazak
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Appendix 6624. Polynucleobacter nec
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Appendix 7Appendix 7List of genomes
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Appendix 748. Bordetella parapertus
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Appendix 7144. Haemophilus somnus14
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Appendix 7240. Prochlorococcus mari
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Appendix 7336. Synechococcus sp. CC
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Downloaded from genome.cshlp.org on
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JOURNAL OF BACTERIOLOGY, June 2008,
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VOL. 190, 2008 P. MIRABILIS GENOME
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2 Nucleic Acids Research, 2008PCR a
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4 Nucleic Acids Research, 2008Table
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8 Nucleic Acids Research, 2008solve
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An Assessment of the Role of DNA Ad
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DAM and Transcriptionpotential of s
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