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

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IntroductionI.1. IntroductionBacteria are unicellular organisms that are the most numerous of all free-living life known toman; there are at least a billion species of bacteria; the number of bacterial cells in the humanbody is ten times that of human cells; and there may be in the range of 10 30 bacterial cellsacross the whole gamut of habitats on Earth. Thus, this group of organisms forms an essentialand dominant component of our ecosystems. Bacteria may be capable of living on a singletype of habitat - a parasitic or symbiotic dependence on a larger host for example - or incomplex and changing habitats such as the soil or transmission from an environmental sourceto an animal host.The range of habitats colonised implies a necessity to code for the entire range of moleculartools to survive under these conditions. However, since biosynthesis of important moleculessuch as proteins is expensive, any bacterium must produce only those that are required forsurvival under its present conditions. This can happen at two levels: (1) streamlined genomesthat code for only those genes and other DNA elements necessary for survival under a givenhabitat; variations can occur, either over long evolutionary time-scales or via gene transfermechanisms; and (2) signal-dependent regulation which ensures that specific genes andproteins are expressed or activated only when required; this would be essential for bacteriathat have to survive under a range of habitats each providing its own set of nutrients andadversaries. For much of this thesis, we primarily consider the second mode of adaptation - byregulation; however, where appropriate we discuss how different bacteria vary their repertoireof regulatory proteins depending on their habitats and lifestyles.The most intuitive and arguably important control point for gene expression is initiation oftranscription. This is controlled by a wide range of molecule types: small-molecules, DNAand proteins. Regulation of transcript elongation and translation at the post-transcriptionalstage offers further layers of control. This stage also introduces RNA molecules as regulatoryagents. Once a protein is produced, its activity can be controlled by post-translationalmodifications: this can feedback to transcriptional and post-transcriptional regulatory stages.In this chapter we discuss insights into transcriptional and post-translational control of geneexpression and protein activity in bacteria - with the greatest emphasis on transcriptional2
egulation owing to the large amount of information available from genome-scale studies.This chapter is organised in the following manner. (1) We begin by introducing transcriptioninitiation and its global control by basal factors. (2) Next we discuss more specific controloffered by the large selection of transcription factors encoded by many bacteria. (3) We thendescribe an important and complex second-messenger signalling mechanism as a nontranscriptionalcontrol system. (4) Following this, we review concepts relating to thespecificity and evolution of the two-component system for transducing signals between thecell surface and downstream output-generating machinery. (5) Finally, we conclude byhighlighting some further aspects of regulation that are otherwise beyond the scope of thischapter.3
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Page 9 and 10: TitlePageFigure 4.5: Catalytic and
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Chapter 2: Transcriptional control
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Chapter 3: Transcriptional and post
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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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