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Evolvability and hierarchy in rewired bacterial gene networks (2008)

M. Isalan ; C. Lemerle ; K. Michalodimitrakis ; [et al.]

Nature Publishing Group (NPG)

In: Nature. 452(7189): 840-5. doi: 10.1038/nature06847.

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Publication Date: 2008-04-19

Description: Sequencing DNA from several organisms has revealed that duplication and drift of existing genes have primarily moulded the contents of a given genome. Though the effect of knocking out or overexpressing a particular gene has been studied in many organisms, no study has systematically explored the effect of adding new links in a biological network. To explore network evolvability, we constructed 598 recombinations of promoters (including regulatory regions) with different transcription or sigma-factor genes in Escherichia coli, added over a wild-type genetic background. Here we show that approximately 95% of new networks are tolerated by the bacteria, that very few alter growth, and that expression level correlates with factor position in the wild-type network hierarchy. Most importantly, we find that certain networks consistently survive over the wild type under various selection pressures. Therefore new links in the network are rarely a barrier for evolution and can even confer a fitness advantage.〈br /〉〈br /〉〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666274/" target="_blank"〉〈img src="https://static.pubmed.gov/portal/portal3rc.fcgi/4089621/img/3977009" border="0"〉〈/a〉 〈a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2666274/" target="_blank"〉This paper as free author manuscript - peer-reviewed and accepted for publication〈/a〉〈br /〉〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Isalan, Mark -- Lemerle, Caroline -- Michalodimitrakis, Konstantinos -- Horn, Carsten -- Beltrao, Pedro -- Raineri, Emanuele -- Garriga-Canut, Mireia -- Serrano, Luis -- 066543/Wellcome Trust/United Kingdom -- England -- Nature. 2008 Apr 17;452(7189):840-5. doi: 10.1038/nature06847.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉EMBL/CRG Systems Biology Research Unit, Centre for Genomic Regulation (CRG), UPF, 08003 Barcelona, Spain. isalan@crg.es〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/18421347" target="_blank"〉PubMed〈/a〉

Keywords: Escherichia coli/*genetics/growth & development/*metabolism ; Escherichia coli Proteins/genetics/metabolism ; *Evolution, Molecular ; Gene Expression Regulation, Bacterial/*genetics ; Gene Regulatory Networks/*genetics ; Genes, Bacterial/genetics ; *Genetic Engineering ; Heat-Shock Response ; Oligonucleotide Array Sequence Analysis ; Open Reading Frames/genetics ; Promoter Regions, Genetic/genetics ; *Selection, Genetic ; Serial Passage ; Sigma Factor/genetics/metabolism ; Transcription Factors/genetics/metabolism

Print ISSN: 0028-0836

Electronic ISSN: 1476-4687

Topics: Biology , Chemistry and Pharmacology , Medicine , Natural Sciences in General , Physics

Published by Nature Publishing Group (NPG)

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Impact of genome reduction on bacterial metabolism and its regulation (2009)

E. Yus ; T. Maier ; K. Michalodimitrakis ; [et al.]

American Association for the Advancement of Science (AAAS)

In: Science. 326(5957): 1263-8. doi: 10.1126/science.1177263.

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Publication Date: 2009-12-08

Description: To understand basic principles of bacterial metabolism organization and regulation, but also the impact of genome size, we systematically studied one of the smallest bacteria, Mycoplasma pneumoniae. A manually curated metabolic network of 189 reactions catalyzed by 129 enzymes allowed the design of a defined, minimal medium with 19 essential nutrients. More than 1300 growth curves were recorded in the presence of various nutrient concentrations. Measurements of biomass indicators, metabolites, and 13C-glucose experiments provided information on directionality, fluxes, and energetics; integration with transcription profiling enabled the global analysis of metabolic regulation. Compared with more complex bacteria, the M. pneumoniae metabolic network has a more linear topology and contains a higher fraction of multifunctional enzymes; general features such as metabolite concentrations, cellular energetics, adaptability, and global gene expression responses are similar, however.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉Yus, Eva -- Maier, Tobias -- Michalodimitrakis, Konstantinos -- van Noort, Vera -- Yamada, Takuji -- Chen, Wei-Hua -- Wodke, Judith A H -- Guell, Marc -- Martinez, Sira -- Bourgeois, Ronan -- Kuhner, Sebastian -- Raineri, Emanuele -- Letunic, Ivica -- Kalinina, Olga V -- Rode, Michaela -- Herrmann, Richard -- Gutierrez-Gallego, Ricardo -- Russell, Robert B -- Gavin, Anne-Claude -- Bork, Peer -- Serrano, Luis -- New York, N.Y. -- Science. 2009 Nov 27;326(5957):1263-8. doi: 10.1126/science.1177263.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Centre for Genomic Regulation (CRG) and Universitat Pompeu Fabra, Avenida Dr. Aiguader 88, 08003 Barcelona, Spain.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/19965476" target="_blank"〉PubMed〈/a〉

Keywords: Adenosine Triphosphate/metabolism ; Bacterial Proteins/*metabolism ; Culture Media ; Energy Metabolism ; Enzymes/genetics/metabolism ; Gene Expression Profiling ; *Gene Expression Regulation, Bacterial ; *Genome, Bacterial ; Glycolysis ; *Metabolic Networks and Pathways ; Mycoplasma pneumoniae/*genetics/growth & development/*metabolism ; RNA, Bacterial/genetics/metabolism ; Signal Transduction ; Systems Biology ; Transcription, Genetic ; rRNA Operon

Print ISSN: 0036-8075

Electronic ISSN: 1095-9203

Topics: Biology , Chemistry and Pharmacology , Computer Science , Medicine , Natural Sciences in General , Physics

Published by American Association for the Advancement of Science (AAAS)

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Modelling and simulating generic RNA-Seq experiments with the flux simulator (2012)

Griebel, T., Zacher, B., Ribeca, P., Raineri, E., Lacroix, V., Guigo, R., Sammeth, M.

Oxford University Press

In: Nucleic Acids Research

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Publication Date: 2012-11-04

Description: High-throughput sequencing of cDNA libraries constructed from cellular RNA complements (RNA-Seq) naturally provides a digital quantitative measurement for every expressed RNA molecule. Nature, impact and mutual interference of biases in different experimental setups are, however, still poorly understood—mostly due to the lack of data from intermediate protocol steps. We analysed multiple RNA-Seq experiments, involving different sample preparation protocols and sequencing platforms: we broke them down into their common—and currently indispensable—technical components (reverse transcription, fragmentation, adapter ligation, PCR amplification, gel segregation and sequencing), investigating how such different steps influence abundance and distribution of the sequenced reads. For each of those steps, we developed universally applicable models, which can be parameterised by empirical attributes of any experimental protocol. Our models are implemented in a computer simulation pipeline called the Flux Simulator, and we show that read distributions generated by different combinations of these models reproduce well corresponding evidence obtained from the corresponding experimental setups. We further demonstrate that our in silico RNA-Seq provides insights about hidden precursors that determine the final configuration of reads along gene bodies; enhancing or compensatory effects that explain apparently controversial observations can be observed. Moreover, our simulations identify hitherto unreported sources of systematic bias from RNA hydrolysis, a fragmentation technique currently employed by most RNA-Seq protocols.

Print ISSN: 0305-1048

Electronic ISSN: 1362-4962

Topics: Biology

Published by Oxford University Press

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