A systems level predictive model for global gene regulation of methanogenesis in a hydrogenotrophic methanogen

Yoon, Sung Ho; Turkarslan, Serdar; Reiss, David J; Pan, Min; Burn, June A.; Costa, Kyle C.; Lie, Thomas J.; Slagel, Joseph; Moritz, Robert L.; Hackett, Murray; Leigh, John A.; Baliga, Nitin S.

doi:10.1101/gr.153916.112

Cited by 32 publications

(26 citation statements)

References 49 publications

(70 reference statements)

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“…Despite this knowledge, the cellular regulators of growth that respond to environmental perturbation remain understudied in H. salinarum and other archaeal species. In particular, the phenotypic impact of mutations to known TFs under alternate stress conditions-and the downstream effect of those mutations on the function of the global regulatory network-remains unclear for H. salinarum ) and many other understudied microorganisms (Yoon et al 2011(Yoon et al , 2013.…”

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confidence: 99%

Detecting differential growth of microbial populations with Gaussian process regression

et al. 2016

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Microbial growth curves are used to study differential effects of media, genetics, and stress on microbial population growth. Consequently, many modeling frameworks exist to capture microbial population growth measurements. However, current models are designed to quantify growth under conditions for which growth has a specific functional form. Extensions to these models are required to quantify the effects of perturbations, which often exhibit nonstandard growth curves. Rather than assume specific functional forms for experimental perturbations, we developed a general and robust model of microbial population growth curves using Gaussian process (GP) regression. GP regression modeling of high-resolution time-series growth data enables accurate quantification of population growth and allows explicit control of effects from other covariates such as genetic background. This framework substantially outperforms commonly used microbial population growth models, particularly when modeling growth data from environmentally stressed populations. We apply the GP growth model and develop statistical tests to quantify the differential effects of environmental perturbations on microbial growth across a large compendium of genotypes in archaea and yeast. This method accurately identifies known transcriptional regulators and implicates novel regulators of growth under standard and stress conditions in the model archaeal organism Halobacterium salinarum. For yeast, our method correctly identifies known phenotypes for a diversity of genetic backgrounds under cyclohexamide stress and also detects previously unidentified oxidative stress sensitivity across a subset of strains. Together, these results demonstrate that the GP models are interpretable, recapitulating biological knowledge of growth response while providing new insights into the relevant parameters affecting microbial population growth.

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confidence: 99%

Detecting differential growth of microbial populations with Gaussian process regression

et al. 2016

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“…Mmp1357 is homologous to the archaeal Ubl protein SAMP, and it is encoded upstream of the mmp1356 gene. According to the transcriptomic tiling array data [35], mmp1357 and mmp1356 are most likely to be co‐transcribed, suggesting that they represent an operon. This genetic association is present in several archaeal lineages [36], including some species of the methanogens ( Methanoregula , Methanocorpusculum , Methanococcus , and Methanosphaerula ), the crenarchaeotes ( Aeropyrum , Hyperthermus , Pyrolobus , Staphylothermus , and Stygioglobus ), and the korarchaeotes ( Korarchaeum ).…”

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confidence: 99%

The putative tRNA 2‐thiouridine synthetase Ncs6 is an essential sulfur carrier in Methanococcus maripaludis

et al. 2014

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Thiolation of carbon-2 of uridine located in the first position of the anticodons of tRNAGlnUUG, tRNAGluUUC, and tRNALysUUU is a conserved RNA modification event requiring the 2-thiouridine synthetase Ncs6/Ctu1 in archaea and eukaryotes. Ncs6/Ctu1 activates uridine by adenylation, but its role in sulfur transfer is unclear. Here we show that Mmp1356, the Ncs6/Ctu1 homolog in the archaeon Methanococcus maripaludis, forms a persulfide enzyme adduct with an active site cysteine; this suggests that Mmp1356 directly participates in sulfur transfer as a persulfide carrier. Transposon mutagenesis shows that Mmp1356 is likely to be an essential protein.

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“…If MA1395 does indeed regulate these genes it could act to sense available nickel in the environment and slow metabolism (via mch and por ) while affecting redox balance (via production of NADH/NADPH and coenzyme F420). A previous study on regulation in Methanococcus maripaludis identified a homolog of MA1395 ( MMP0719 ) as being coexpressed with mch along with the methyltransferase mtr , the energy conserving hydrogenase ehb and genes involved in pyrophosphate uptake ( ppaC ) and purine biosynthesis ( purP ) [74]. Together these suggest an ancient role for MA1395 that needs to be further studied.…”

Section: Discussionmentioning

confidence: 99%

Genome-wide gene expression and RNA half-life measurements allow predictions of regulation and metabolic behavior in Methanosarcina acetivorans

et al. 2016

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BackgroundWhile a few studies on the variations in mRNA expression and half-lives measured under different growth conditions have been used to predict patterns of regulation in bacterial organisms, the extent to which this information can also play a role in defining metabolic phenotypes has yet to be examined systematically. Here we present the first comprehensive study for a model methanogen.ResultsWe use expression and half-life data for the methanogen Methanosarcina acetivorans growing on fast- and slow-growth substrates to examine the regulation of its genes. Unlike Escherichia coli where only small shifts in half-lives were observed, we found that most mRNA have significantly longer half-lives for slow growth on acetate compared to fast growth on methanol or trimethylamine. Interestingly, half-life shifts are not uniform across functional classes of enzymes, suggesting the existence of a selective stabilization mechanism for mRNAs. Using the transcriptomics data we determined whether transcription or degradation rate controls the change in transcript abundance. Degradation was found to control abundance for about half of the metabolic genes underscoring its role in regulating metabolism. Genes involved in half of the metabolic reactions were found to be differentially expressed among the substrates suggesting the existence of drastically different metabolic phenotypes that extend beyond just the methanogenesis pathways. By integrating expression data with an updated metabolic model of the organism (iST807) significant differences in pathway flux and production of metabolites were predicted for the three growth substrates.ConclusionsThis study provides the first global picture of differential expression and half-lives for a class II methanogen, as well as provides the first evidence in a single organism that drastic genome-wide shifts in RNA half-lives can be modulated by growth substrate. We determined which genes in each metabolic pathway control the flux and classified them as regulated by transcription (e.g. transcription factor) or degradation (e.g. post-transcriptional modification). We found that more than half of genes in metabolism were controlled by degradation. Our results suggest that M. acetivorans employs extensive post-transcriptional regulation to optimize key metabolic steps, and more generally that degradation could play a much greater role in optimizing an organism’s metabolism than previously thought.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-3219-8) contains supplementary material, which is available to authorized users.

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A systems level predictive model for global gene regulation of methanogenesis in a hydrogenotrophic methanogen

Cited by 32 publications

References 49 publications

Detecting differential growth of microbial populations with Gaussian process regression

Detecting differential growth of microbial populations with Gaussian process regression

The putative tRNA 2‐thiouridine synthetase Ncs6 is an essential sulfur carrier in Methanococcus maripaludis

Genome-wide gene expression and RNA half-life measurements allow predictions of regulation and metabolic behavior in Methanosarcina acetivorans

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