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Transhydrogenase Promotes the Robustness and Evolvability of Deficient in NADPH Production


The structure of biological networks, like traffic systems or the Internet, features few hubs connected by numerous components. Though the conservation and high connectivity of hubs serve as key junctions to promote network expansion, addition or removal of connections surrounding hubs may disturb the whole system through their global linkage. How do biological networks mitigate hub perturbations during evolution? Using metabolism as an example, we studied the physiological and evolutionary consequences of genetically perturbed production of a hub metabolite NADPH in E. coli. We found that the expression of mTH, a phylogenetically conserved enzyme, was immediately upregulated and essential to counteract the hub perturbation. Moreover, long-term evolution of this pathway-modified E. coli in glucose growth media recurrently selected for mTH-upregulating mutations to restore the NADPH balance in all twelve replicate populations, regardless of several alternative solutions suggested in the literature. Corroborated by similar findings from laboratory evolution of a highly diverged species M. extorquens, our study suggests that mechanisms dedicated to mitigating hub perturbations promote both the robustness and evolvability of biological networks.


Vyšlo v časopise: Transhydrogenase Promotes the Robustness and Evolvability of Deficient in NADPH Production. PLoS Genet 11(2): e32767. doi:10.1371/journal.pgen.1005007
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005007

Souhrn

The structure of biological networks, like traffic systems or the Internet, features few hubs connected by numerous components. Though the conservation and high connectivity of hubs serve as key junctions to promote network expansion, addition or removal of connections surrounding hubs may disturb the whole system through their global linkage. How do biological networks mitigate hub perturbations during evolution? Using metabolism as an example, we studied the physiological and evolutionary consequences of genetically perturbed production of a hub metabolite NADPH in E. coli. We found that the expression of mTH, a phylogenetically conserved enzyme, was immediately upregulated and essential to counteract the hub perturbation. Moreover, long-term evolution of this pathway-modified E. coli in glucose growth media recurrently selected for mTH-upregulating mutations to restore the NADPH balance in all twelve replicate populations, regardless of several alternative solutions suggested in the literature. Corroborated by similar findings from laboratory evolution of a highly diverged species M. extorquens, our study suggests that mechanisms dedicated to mitigating hub perturbations promote both the robustness and evolvability of biological networks.


Zdroje

1. Barabasi AL, Oltvai ZN (2004) Network biology: understanding the cell's functional organization. Nat Rev Genet 5: 101–113. 14735121

2. Jeong H, Tombor B, Albert R, Oltvai ZN, Barabasi AL (2000) The large-scale organization of metabolic networks. Nature 407: 651–654. 11034217

3. Kim PJ, Lee DY, Kim TY, Lee KH, Jeong H, et al. (2007) Metabolite essentiality elucidates robustness of Escherichia coli metabolism. Proc Natl Acad Sci USA 104: 13638–13642. 17698812

4. Schmidt S, Sunyaev S, Bork P, Dandekar T (2003) Metabolites: a helping hand for pathway evolution? Trends Biochem Sci 28: 336–341. 12826406

5. Pfeiffer T, Soyer OS, Bonhoeffer S (2005) The evolution of connectivity in metabolic networks. PLoS Biol 3: e228. 16000019

6. Singh R, Mailloux RJ, Puiseux-Dao S, Appanna VD (2007) Oxidative stress evokes a metabolic adaptation that favors increased NADPH synthesis and decreased NADH production in Pseudomonas fluorescens. J Bacteriol 189: 6665–6675. 17573472

7. Rui B, Shen T, Zhou H, Liu J, Chen J, et al. (2010) A systematic investigation of Escherichia coli central carbon metabolism in response to superoxide stress. BMC Syst Biol 4: 122. doi: 10.1186/1752-0509-4-122 20809933

8. Minard KI, McAlister-Henn L (2005) Sources of NADPH in yeast vary with carbon source. J Biol Chem 280: 39890–39896. 16179340

9. Federowicz S, Kim D, Ebrahim A, Lerman J, Nagarajan H, et al. (2014) Determining the control circuitry of redox metabolism at the genome-scale. PLoS Genet 10: e1004264. doi: 10.1371/journal.pgen.1004264 24699140

10. Chou HH, Chiu HC, Delaney NF, Segre D, Marx CJ (2011) Diminishing returns epistasis among beneficial mutations decelerates adaptation. Science 332: 1190–1192. doi: 10.1126/science.1203799 21636771

11. Auriol C, Bestel-Corre G, Claude JB, Soucaille P, Meynial-Salles I (2011) Stress-induced evolution of Escherichia coli points to original concepts in respiratory cofactor selectivity. Proc Natl Acad Sci USA 108: 1278–1283. doi: 10.1073/pnas.1010431108 21205901

12. Charusanti P, Conrad TM, Knight EM, Venkataraman K, Fong NL, et al. (2010) Genetic basis of growth adaptation of Escherichia coli after deletion of pgi, a major metabolic gene. PLoSGenet 6: e1001186.

13. Kitano H (2004) Biological robustness. Nat Rev Genet 5: 826–837. 15520792

14. Fuhrer T, Sauer U (2009) Different biochemical mechanisms ensure network-wide balancing of reducing equivalents in microbial metabolism. J Bacteriol 191: 2112–2121. doi: 10.1128/JB.01523-08 19181802

15. Fong SS, Nanchen A, Palsson BO, Sauer U (2006) Latent pathway activation and increased pathway capacity enable Escherichia coli adaptation to loss of key metabolic enzymes. JBiolChem 281: 8024–8033. 16319065

16. Bakker BM, Overkamp KM, van Maris AJ, Kotter P, Luttik MA, et al. (2001) Stoichiometry and compartmentation of NADH metabolism in Saccharomyces cerevisiae. FEMS Microbiol Rev 25: 15–37. 11152939

17. Ruhl M, Le Coq D, Aymerich S, Sauer U (2012) 13C-flux analysis reveals NADPH-balancing transhydrogenation cycles in stationary phase of nitrogen-starving Bacillus subtilis. J Biol Chem 287: 27959–27970. doi: 10.1074/jbc.M112.366492 22740702

18. Overkamp KM, Bakker BM, Steensma HY, van Dijken JP, Pronk JT (2002) Two mechanisms for oxidation of cytosolic NADPH by Kluyveromyces lactis mitochondria. Yeast 19: 813–824. 12112236

19. Sauer U, Canonaco F, Heri S, Perrenoud A, Fischer E (2004) The soluble and membrane-bound transhydrogenases UdhA and PntAB have divergent functions in NADPH metabolism of Escherichia coli. J Biol Chem 279: 6613–6619. 14660605

20. Zhao J, Baba T, Mori H, Shimizu K (2004) Effect of zwf gene knockout on the metabolism of Escherichia coli grown on glucose or acetate. Metab Eng 6: 164–174. 15113569

21. Elena SF, Lenski RE (2003) Evolution experiments with microorganisms: the dynamics and genetic bases of adaptation. NatRevGenet 4: 457–469.

22. Hayashi K, Morooka N, Yamamoto Y, Fujita K, Isono K, et al. (2006) Highly accurate genome sequences of Escherichia coli K-12 strains MG1655 and W3110. Mol Syst Biol 2: 2006 0007. 16788596

23. Freddolino PL, Amini S, Tavazoie S (2012) Newly identified genetic variations in common Escherichia coli MG1655 stock cultures. J Bacteriol 194: 303–306. doi: 10.1128/JB.06087-11 22081388

24. Barker CS, Pruss BM, Matsumura P (2004) Increased motility of Escherichia coli by insertion sequence element integration into the regulatory region of the flhD operon. J Bacteriol 186: 7529–7537. 15516564

25. Wielgoss S, Barrick JE, Tenaillon O, Cruveiller S, Chane-Woon-Ming B, et al. (2011) Mutation rate inferred from synonymous substitutions in a long-term evolution experiment with Escherichia coli. G3 (Bethesda) 1: 183–186. 22207905

26. Hershberg R, Petrov DA (2010) Evidence that mutation is universally biased towards AT in bacteria. PLoS Genet 6: e1001115. doi: 10.1371/journal.pgen.1001115 20838599

27. Conrad TM, Frazier M, Joyce AR, Cho BK, Knight EM, et al. (2010) RNA polymerase mutants found through adaptive evolution reprogram Escherichia coli for optimal growth in minimal media. Proc Natl Acad Sci USA 107: 20500–20505. doi: 10.1073/pnas.0911253107 21057108

28. Soupene E, van Heeswijk WC, Plumbridge J, Stewart V, Bertenthal D, et al. (2003) Physiological studies of Escherichia coli strain MG1655: growth defects and apparent cross-regulation of gene expression. J Bacteriol 185: 5611–5626. 12949114

29. Zhou J, Rudd KE (2013) EcoGene 3.0. Nucleic Acids Res 41: D613–624. doi: 10.1093/nar/gks1235 23197660

30. Lin RJ, Capage M, Hill CW (1984) A repetitive DNA sequence, rhs, responsible for duplications within the Escherichia coli K-12 chromosome. J Mol Biol 177: 1–18. 6086936

31. Chubukov V, Gerosa L, Kochanowski K, Sauer U (2014) Coordination of microbial metabolism. Nat Rev Microbiol 12: 327–340. doi: 10.1038/nrmicro3238 24658329

32. Woods R, Schneider D, Winkworth CL, Riley MA, Lenski RE (2006) Tests of parallel molecular evolution in a long-term experiment with Escherichia coli. Proc Natl Acad Sci USA 103: 9107–9112. 16751270

33. Studier FW, Daegelen P, Lenski RE, Maslov S, Kim JF (2009) Understanding the differences between genome sequences of Escherichia coli B strains REL606 and BL21(DE3) and comparison of the E. coli B and K-12 genomes. J Mol Biol 394: 653–680. doi: 10.1016/j.jmb.2009.09.021 19765592

34. Shimada T, Fujita N, Yamamoto K, Ishihama A (2011) Novel roles of cAMP receptor protein (CRP) in regulation of transport and metabolism of carbon sources. PLoS One 6: e20081. doi: 10.1371/journal.pone.0020081 21673794

35. Wolfe AJ (2005) The acetate switch. Microbiol Mol Biol Rev 69: 12–50. 15755952

36. Zaslaver A, Bren A, Ronen M, Itzkovitz S, Kikoin I, et al. (2006) A comprehensive library of fluorescent transcriptional reporters for Escherichia coli. Nature Methods 3: 623–628. 16862137

37. Gerosa L, Kochanowski K, Heinemann M, Sauer U (2013) Dissecting specific and global transcriptional regulation of bacterial gene expression. Mol Syst Biol 9: 658. doi: 10.1038/msb.2013.14 23591774

38. Haverkorn van Rijsewijk BRB (2012) Transcriptional regulation of central metabolism in Escherichia coli. Ph.D. Thesis, ETH Zürich. Available:http://e-collection.library.ethz.ch/eserv/eth:5477/eth-5477-02.pdf. Accessed 11 September 2014.

39. Flores S, Flores N, de Anda R, Gonzalez A, Escalante A, et al. (2005) Nutrient-scavenging stress response in an Escherichia coli strain lacking the phosphoenolpyruvate: carbohydrate phosphotransferase system, as explored by gene expression profile analysis. J Mol Microbiol Biotechnol 10: 51–63. 16491026

40. Zeppenfeld T, Larisch C, Lengeler JW, Jahreis K (2000) Glucose transporter mutants of Escherichia coli K-12 with changes in substrate recognition of IICB(Glc) and induction behavior of the ptsG gene. J Bacteriol 182: 4443–4452. 10913077

41. Yao R, Hirose Y, Sarkar D, Nakahigashi K, Ye Q, et al. (2011) Catabolic regulation analysis of Escherichia coli and its crp, mlc, mgsA, pgi and ptsG mutants. Microb Cell Fact 10: 67. doi: 10.1186/1475-2859-10-67 21831320

42. Steinsiek S, Bettenbrock K (2012) Glucose transport in Escherichia coli mutant strains with defects in sugar transport systems. J Bacteriol 194: 5897–5908. doi: 10.1128/JB.01502-12 22923596

43. Moreira dos Santos M, Raghevendran V, Kotter P, Olsson L, Nielsen J (2004) Manipulation of malic enzyme in Saccharomyces cerevisiae for increasing NADPH production capacity aerobically in different cellular compartments. Metab Eng 6: 352–363. 15491864

44. Mori S, Kawai S, Shi F, Mikami B, Murata K (2005) Molecular conversion of NAD kinase to NADH kinase through single amino acid residue substitution. J Biol Chem 280: 24104–24112. 15855156

45. Bocanegra JA, Scrutton NS, Perham RN (1993) Creation of an NADP-dependent pyruvate dehydrogenase multienzyme complex by protein engineering. Biochemistry 32: 2737–2740. 8457541

46. Nishiyama M, Birktoft JJ, Beppu T (1993) Alteration of coenzyme specificity of malate dehydrogenase from Thermus flavus by site-directed mutagenesis. J Biol Chem 268: 4656–4660. 8444839

47. Lakshmanan M, Chung BK, Liu C, Kim SW, Lee DY (2013) Cofactor modification analysis: a computational framework to identify cofactor specificity engineering targets for strain improvement. J Bioinform Comput Biol 11: 1343006. doi: 10.1142/S0219720013430063 24372035

48. Woods RJ, Barrick JE, Cooper TF, Shrestha U, Kauth MR, et al. (2011) Second-order selection for evolvability in a large Escherichia coli population. Science 331: 1433–1436. doi: 10.1126/science.1198914 21415350

49. Carroll SM, Marx CJ (2013) Evolution after introduction of a novel metabolic pathway consistently leads to restoration of wild-type physiology. PLoS Genet 9: e1003427. doi: 10.1371/journal.pgen.1003427 23593025

50. Battistuzzi FU, Feijao A, Hedges SB (2004) A genomic timescale of prokaryote evolution: insights into the origin of methanogenesis, phototrophy, and the colonization of land. BMC Evol Biol 4: 44. 15535883

51. Vuilleumier S, Chistoserdova L, Lee MC, Bringel F, Lajus A, et al. (2009) Methylobacterium genome sequences: a reference blueprint to investigate microbial metabolism of C1 compounds from natural and industrial sources. PLoS ONE 4: e5584. doi: 10.1371/journal.pone.0005584 19440302

52. Stern DL (2013) The genetic causes of convergent evolution. Nat Rev Genet 14: 751–764. doi: 10.1038/nrg3483 24105273

53. Wood TE, Burke JM, Rieseberg LH (2005) Parallel genotypic adaptation: when evolution repeats itself. Genetica 123: 157–170. 15881688

54. Rydstrom J (2006) Mitochondrial NADPH, transhydrogenase and disease. BiochimBiophysActa 1757: 721–726. 16730324

55. Orr HA (2005) The genetic theory of adaptation: a brief history. Nat Rev Genet 6: 119–127. 15716908

56. Bloom JD, Labthavikul ST, Otey CR, Arnold FH (2006) Protein stability promotes evolvability. Proc Natl Acad Sci USA 103: 5869–5874. 16581913

57. Rorick MM, Wagner GP (2011) Protein structural modularity and robustness are associated with evolvability. Genome Biol Evol 3: 456–475. doi: 10.1093/gbe/evr046 21602570

58. Isalan M, Lemerle C, Michalodimitrakis K, Horn C, Beltrao P, et al. (2008) Evolvability and hierarchy in rewired bacterial gene networks. Nature 452: 840–845. doi: 10.1038/nature06847 18421347

59. Payne JL, Wagner A (2014) The robustness and evolvability of transcription factor binding sites. Science 343: 875–877. doi: 10.1126/science.1249046 24558158

60. Rutherford SL, Lindquist S (1998) Hsp90 as a capacitor for morphological evolution. Nature 396: 336–342. 9845070

61. Treves DS, Manning S, Adams J (1998) Repeated evolution of an acetate-crossfeeding polymorphism in long-term populations of Escherichia coli. Mol Biol Evol 15: 789–797. 9656481

62. Herron MD, Doebeli M (2013) Parallel evolutionary dynamics of adaptive diversification in Escherichia coli. PLoS Biol 11: e1001490. doi: 10.1371/journal.pbio.1001490 23431270

63. Oh MK, Rohlin L, Kao KC, Liao JC (2002) Global expression profiling of acetate-grown Escherichia coli. J Biol Chem 277: 13175–13183. 11815613

64. Chen X, Li S, Liu L (2014) Engineering redox balance through cofactor systems. Trends Biotechnol 32: 337–343. doi: 10.1016/j.tibtech.2014.04.003 24794722

65. Philippe N, Alcaraz JP, Coursange E, Geiselmann J, Schneider D (2004) Improvement of pCVD442, a suicide plasmid for gene allele exchange in bacteria. Plasmid 51: 246–255. 15109831

66. Heckman KL, Pease LR (2007) Gene splicing and mutagenesis by PCR-driven overlap extension. Nat Protoc 2: 924–932. 17446874

67. Lee MC, Chou HH, Marx CJ (2009) Asymmetric, bi-modal tradeoffs during adaptation of Methylobacterium to distinct growth substrates. Evolution 63: 2816–2830. doi: 10.1111/j.1558-5646.2009.00757.x 19545267

68. Brunner M, Bujard H (1987) Promoter recognition and promoter strength in the Escherichia coli system. EMBO J 6: 3139–3144. 2961560

69. Volkmer B, Heinemann M (2011) Condition-dependent cell volume and concentration of Escherichia coli to facilitate data conversion for systems biology modeling. PLoS One 6: e23126. doi: 10.1371/journal.pone.0023126 21829590

70. Delaney NF, Kaczmarek ME, Ward LM, Swanson PK, Lee MC, et al. (2013) Development of an optimized medium, strain and high-throughput culturing methods for Methylobacterium extorquens. PLoS One 8: e62957. doi: 10.1371/journal.pone.0062957 23646164

71. Bradford MM (1976) A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem 72: 248–254. 942051

72. Chou HH, Berthet J, Marx CJ (2009) Fast growth increases the selective advantage of a mutation arising recurrently during evolution under metal limitation. PLoS Genet 5: e1000652. doi: 10.1371/journal.pgen.1000652 19763169

73. Chou HH, Delaney NF, Draghi JA, Marx CJ (2014) Mapping the fitness landscape of gene expression uncovers the cause of antagonism and sign epistasis between adaptive mutations. PLoS Genet 10: e1004149. doi: 10.1371/journal.pgen.1004149 24586190

74. Chou HH, Marx CJ (2012) Optimization of gene expression through divergent mutational paths. Cell Reports 1: 133–140. doi: 10.1016/j.celrep.2011.12.003 22832162

75. Buescher JM, Moco S, Sauer U, Zamboni N (2010) Ultrahigh performance liquid chromatography-tandem mass spectrometry method for fast and robust quantification of anionic and aromatic metabolites. Anal Chem 82: 4403–4412. doi: 10.1021/ac100101d 20433152

76. Ciccarelli FD, Doerks T, von Mering C, Creevey CJ, Snel B, et al. (2006) Toward automatic reconstruction of a highly resolved tree of life. Science 311: 1283–1287. 16513982

77. Maglott D, Ostell J, Pruitt KD, Tatusova T (2011) Entrez Gene: gene-centered information at NCBI. Nucleic Acids Res 39: D52–57. doi: 10.1093/nar/gkq1237 21115458

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