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

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Chapter 1: Global regulators of bacterial transcription initiation(A)(B)AT content (%) of upstream region0 20 40 60 80 100pseudo lead non!leadDifference between AT content ofupstream region and ORF!40 !20 0 20 40pseudo lead non!lead(C)(D)AT content (%) of upstream region0 20 40 60 80oldnewDifference between AT content ofupstream region and ORF!40 !20 0 20oldnewFigure 1.3. AT content upstream of pseudogenes. (A) AT content upstream of pseudogenes, bonafidelead and non-lead genes. (B) Difference in AT content between upstream region and gene body forpseudogenes, lead and non-lead genes. (C) AT content upstream of ‘new’ and ‘old’ pseudogenes. (D)Difference in AT content between upstream region and gene body for new and old pseudogenes. Alldata cover 59 genomes in our dataset with pseudogene predictions.process of pseudogene formation is associated with degeneration of the high AT-contentsignal that is characteristic of transcription initiation.Secondly, we tested if there is any difference in the AT-content signal between ‘new’ and‘old’ pseudogenes (Echols et al. 2002). These two groups of pseudogenes can bedifferentiated using codon adaptation indices (CAI). We obtained a measure of the CAI foreach pseudogene, as a Z-score against the distribution of CAI values obtained for all bonafideORFs in the corresponding genome. ‘New’ pseudogenes were defined as those whose CAI34
Chapter 1: Global regulators of bacterial transcription initiationvalues were within 1 standard deviation from the mean for the ORFs in the genome; ‘old’pseudogenes had CAI values less than 2 standard deviations below the mean. Clearly, newpseudogenes have statistically-significantly higher AT-content (PW < 2.2 x 10 -16 ; Figure 1.3C)as well as upstream sequence–ORF AT-content difference (PW = 1.8 x 10 -5 ; Figure 1.3D) thanold pseudogenes. However, it must be noted that even for new pseudogenes, these measuresare far less than those for bonafide lead ORFs. This implies that the very creation of apseudogene is associated with a significant decay in the upstream AT-content. Establishmentof the pseudogene leads to further fall in this measure, though within limits probablyestablished by the properties of the genome in question.Finally, we investigated whether pseudogenes that contain tandem repeats differ in theirupstream AT-content from other pseudogenes. This part of our study was inspired by a recentwork that showed that pseudogenes that are formed due to tandem repeats in theendosymbiont Buchnera aphidicola do produce functional proteins via transcriptionalslippage (Tamas et al. 2008). This conclusively shows that these pseudogenes aretranscriptionally (and translationally) active. There is little difference in the AT-contents ofupstream regions and the corresponding ORFs between pseudogenes with and without tandemrepeats (PW = 0.4). However, the absolute AT-content is extremely high for those with tandemrepeats (PW < 2.2 x 10 -16 respectively for the two comparisons; Appendix 1.4). This is likely aconsequence of a generally high AT-content of these genomes. In fact, Buchnera genomeshave between 70 and 80% genomic AT-content. Further, 80% (259 / 325) of pseudogenes withtandem repeats have A / T repeats. Thus, given that functional conversion of pseudogenes viatranscriptional slippage is not an efficient mechanism, we propose that the high AT-content ofthese genomes / genomic regions in general precludes the necessity for special evolutionaryprocesses in transcribing these genes.In total, results presented so far complement other published data in establishing the role ofhigh AT-content in initiating transcription. This has been explained by the increasedpropensity of transcription factors to bind to AT-rich regions. In addition, we anticipate thathigh AT-content would afford relatively easy unwinding of the DNA, thus permitting smoothtranscription initiation.35
Page 3 and 4: Statement of lengthThis thesis does
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Page 7 and 8: Table of ContentsTitlePagesIntroduc
Page 9 and 10: TitlePageFigure 4.5: Catalytic and
Page 11 and 12: IntroductionFunctional and comparat
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Page 15 and 16: (A) Closed complex formationRNA pol
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Page 19 and 20: I.3. Transcription factors: domain
Page 21 and 22: I.4. Transcriptional regulatory net
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Page 31 and 32: transcriptional initiation by c-di-
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Page 35 and 36: I.7. ConclusionIn this chapter, we
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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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JOURNAL OF BACTERIOLOGY, June 2008,
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VOL. 190, 2008 P. MIRABILIS GENOME
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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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