Journal of Molecular Evolution

, Volume 59, Issue 2, pp 158–176 | Cite as

Phylogenetic Analysis of Proteins Associated in the Four Major Energy Metabolism Systems: Photosynthesis, Aerobic Respiration, Denitrification, and Sulfur Respiration

  • Takeshi Tomiki
  • Naruya Saitou


The four electron transfer energy metabolism systems, photosynthesis, aerobic respiration, denitrification, and sulfur respiration, are thought to be evolutionarily related because of the similarity of electron transfer patterns and the existence of some homologous proteins. How these systems have evolved is elusive. We therefore conducted a comprehensive homology search using PSI-BLAST, and phylogenetic analyses were conducted for the three homologous groups (groups 1–3) based on multiple alignments of domains defined in the Pfam database. There are five electron transfer types important for catalytic reaction in group 1, and many proteins bind molybdenum. Deletions of two domains led to loss of the function of binding molybdenum and ferredoxin, and these deletions seem to be critical for the electron transfer pattern changes in group 1. Two types of electron transfer were found in group 2, and all its member proteins bind siroheme and ferredoxin. Insertion of the pyridine nucleotide disulfide oxidoreductase domain seemed to be the critical point for the electron transfer pattern change in this group. The proteins belonging to group 3 are all flavin enzymes, and they bind flavin adenine dinucleotide (FAD) or flavin mononucleotide (FMN). Types of electron transfer in this group are divergent, but there are two common characteristics. NAD(P)H works as an electron donor or acceptor, and FAD or FMN transfers electrons from/to NAD(P)H. Electron transfer functions might be added to these common characteristics by the addition of functional domains through the evolution of group 3 proteins. Based on the phylogenetic analyses in this study and previous studies, we inferred the phylogeny of the energy metabolism systems as follows: photosynthesis (and possibly aerobic respiration) and the sulfur/nitrogen assimilation system first diverged, then the sulfur/nitrogen dissimilation system was produced from the latter system.


Energy metabolism Photosynthesis Aerobic respiration Denitrification Sulfur respiration Protein phylogeny PSI-BLAST Pfam Tree superimposition 



We are grateful to Dr. Hiromi Suzuki of Meiji University for helping us in the initial part of this study. We appreciate Dr. Takeshi Kawabata of NAIST for advising us of the PSI-BLAST homology search method and helping us to conduct it. Color version of all figures is available at∼tomiki/JME_metabolism/.


  1. Altschul, SF, Madden, TL, Schaffer, AA, Zhang, J, Zhang, Z, Miller, W, Lipman, DJ 1997Gapped BLAST and PSI-BLAST: A new generation of protein database search programsNucleic Acids Res2533893402PubMedGoogle Scholar
  2. Andersson, SG, Zomorodipour, A, Andersson, JO, Sicheritz-Ponten, T, Alsmark, UC, Podowski, RM, Naslund, AK, Eriksson, AS, Winkler, HH, Kurland, CG 1998The genome sequence of Rickettsia prowazekii and the origin of mitochondriaNature396133140CrossRefPubMedGoogle Scholar
  3. Avila, J, Perez, MD, Brito, N, Gonzalez, C, Siverio, JM 1995Cloning and disruption of the YNR1 gene encoding the nitrate reductase apoenzyme of the yeast Hansenula polymorphaFEBS Lett366137142PubMedGoogle Scholar
  4. Bateman, A, Birney, E, Cerruti, L, Durbin, R, Etwiller, L, Eddy, SR, Griffiths-Jones, S, Howe, KL, Marshall, M, Sonnhammer, EL 2002The Pfam protein families databaseNucleic Acids Res30276280CrossRefPubMedGoogle Scholar
  5. Bekker, A, Holland, HD, Wang, PL, Rumble, III D, Stein, HJ, Hannah, JL, Coetzee, LL, Beukes, NJ 2004Dating the rise of atmospheric oxygenNature427117120PubMedGoogle Scholar
  6. Berry, EA, Guergova-Kuras, M, Huang, LS, Crofts, AR 2000Structure and function of cytochrome be complexesAnnu Rev Biochem6910051075CrossRefPubMedGoogle Scholar
  7. Boeckmann, B, Bairoch, A, Apweiler, R, Blatter, MC, Estreicher, A, Gasteiger, E, Martin, MJ, Michoud, K, O’Donovan, C, Phan, I, Pilbout, S, Schneider, M 2003The SWISS-PROT protein knowledge base and its supplement TrEMBL in 2003Nucleic Acids Res31365370CrossRefPubMedGoogle Scholar
  8. Boyington, JC, Gladyshev, VN, Khangulov, SV, Stadtman, TC, Sun, PD 1997Crystal structure of formate dehydrogenase H: catalysis involving Mo, molybdopterin, selenocysteine, and an Fe4 S4 clusterScience27513051308CrossRefPubMedGoogle Scholar
  9. Breton, J, Berks, BC, Reilly, A, Thomson, AJ, Ferguson, SJ, Richardson, DJ 1994Characterization of the paramagnetic iron-containing redox centres of Thiosphaera pantotropha periplasmic nitrate reductaseFEBS Lett3457680PubMedGoogle Scholar
  10. Butler, CS, Charnock, JM, Bennett, B, Sears, HJ, Reilly, AJ, Ferguson, SJ, Garner, CD, Lowe, DJ, Thomson, AJ, Berks, BC, Richardson, DJ 1999Models for molybdenum coordination during the catalytic cycle of periplasmic nitrate reductase from Paracoccus denitrificans derived from EPR and EXAFS spectroscopyBiochemistry3890009012CrossRefPubMedGoogle Scholar
  11. Crane, BR, Getzoff, ED 1996The relationship between structure and function for the sulfite reductasesCurr Opin Struct Biol6744756PubMedGoogle Scholar
  12. Crane, BR, Siegel, LM, Getzoff, ED 1995Sulfite reductase structure at 1.6 A: Evolution and catalysis for reduction of inorganic anionsScience2705967PubMedGoogle Scholar
  13. Crane, BR, Siegel, LM, Getzoff, ED 1997Probing the catalytic mechanism of sulfite reductase by X-ray crystallography: Structures of the Escherichia coli hemoprotein in complex with substrates, inhibitors, intermediates, and productsBiochemistry361212012137PubMedGoogle Scholar
  14. Crawford, NM, Smith, M, Bellissimo, D, Davis, RW 1988Sequence and nitrate regulation of the Arabidopsis thaliana mRNA encoding nitrate reductase, a metalloflavoprotein with three functional domainsProc Natl Acad Sci USA8550065010PubMedGoogle Scholar
  15. Czjzek, M, Dos Santos, JP, Pommier, J, Giordano, G, Mejean, V, Haser, R 1998Crystal structure of oxidized trimethylamine N-oxide reductase from Shewanella massilia at 2.5 A resolutionJ Mol Biol284435447PubMedGoogle Scholar
  16. Dias, JM, Than, ME, Humm, A, Huber, R, Bourenkov, GP, Bartunik, HD, Bursakov, S, Calvete, J, Caldeira, J, Carneiro, C, Moura, JJ, Moura, I, Romao, MJ 1999Crystal structure of the first dissimilatory nitrate reductase at 1.9 A solved by MAD methodsStruct Fold Des76579Google Scholar
  17. Finel, M 1998Organization and evolution of structural elements within complex IBiochim Biophys Acta1364112121PubMedGoogle Scholar
  18. Hauska, G, Nitschke, W, Herrmann, RG 1988Amino acid identities in the three redox center carrying polypeptides of cytochrome bc1/b6 f complexesJ Bioenerg Biomembr20211228PubMedGoogle Scholar
  19. Jormakka, M, Tornroth, S, Byrne, B, Iwata, S 2002Molecular basis of proton motive force generation: Structure of formate dehydrogenase-NScience29518631868CrossRefPubMedGoogle Scholar
  20. Kanehisa, M, Goto, S, Kawashima, S, Nakaya, A 2002The KEGG databases at GenomeNetNucleic Acids Res304246CrossRefPubMedGoogle Scholar
  21. Krafft, T, Bokranz, M, Klimmek, O, Schroder, I, Fahrenholz, F, Kojro, E, Kroger, A 1992Cloning and nucleotide sequence of the psrA gene of Wolinella succinogenes polysulphide reductaseEur J Biochem206503510PubMedGoogle Scholar
  22. Kumar, S, Tamura, K, Jakobsen, IB, Nei, M 2001MEGA2: Molecular evolutionary genetics analysis softwareBioinformatics1712441245CrossRefPubMedGoogle Scholar
  23. Larsen, O, Lien, T, Birkeland, NK 1999Dissimilatory sulfite reductase from Archaeoglobus profundus and Desulfotomaculum thermocisternum: Phylogenetic and structural implications from gene sequencesExtremophiles36370PubMedGoogle Scholar
  24. Li, HK, Temple, C, Rajagopalan, KV, Schindelin, H 2000The 1.3 A crystal structure of Rhodobacter sphaeroides dimethyl sulfoxide reveals two distinct molybdenum coordination environmentsJ Am Chem Soc12276737680Google Scholar
  25. Lu, G, Campbell, WH, Schneider, G, Lindqvist, Y 1994Crystal structure of the FAD-containing fragment of corn nitrate reductase at 2.5 A resolution: Relationship to other flavoprotein reductasesStructure2809821PubMedGoogle Scholar
  26. Lu, G, Lindqvist, Y, Schneider, G, Dwivedi, U, Campbell, W 1995Structural studies on corn nitrate reductase: refined structure of the cytochrome b reductase fragment at 2.5 A, its ADP complex and an active-site mutant and modeling of the cytochrome b domainJ Mol Biol248931948PubMedGoogle Scholar
  27. Magalon, A, Asso, M, Guigliarelli, B, Rothery, RA, Bertrand, P, Giordano, G, Blasco, F 1998Molybdenum cofactor properties and [Fe-S] cluster coordination in Escherichia coli nitrate reductase A: investigation by site-directed mutagenesis of the conserved his-50 residue in the NarG subunitBiochemistry3773637370CrossRefPubMedGoogle Scholar
  28. McAlpine, AS, McEwan, AG, Bailey, S 1998The high resolution crystal structure of DMSO reductase in complex with DMSOJ Mol Biol275613623PubMedGoogle Scholar
  29. Mogi, T, Tsubaki, M, Hori, H, Miyoshi, H, Nakamura, H, Anraku, Y 1998Two terminal quinol oxidase families in Escherichia coli: Variations on molecular machinery for dioxygen reductionJ Biochem Mol Biol Biophys279110Google Scholar
  30. Moreno-Vivian, C, Cabello, P, Martinez-Luque, M, Blasco, R, Castillo, F 1999Prokaryotic nitrate reduction: Molecular properties and functional distinction among bacterial nitrate reductasesJ Bacteriol18165736584PubMedGoogle Scholar
  31. Ohnishi, T 1998Iron–sulfur clusters/semiquinones in complex IBiochim Biophys Acta1364186206PubMedGoogle Scholar
  32. Ota, S, Saitou, N 1999Phylogenetic relationship of muscle tissues deduced from superimposition of gene treesMol Biol Evol16856867PubMedGoogle Scholar
  33. Park, J, Karplus, K, Barrett, C, Hughey, R, Haussler, D, Hubbard, T, Chothia, C 1998Sequence comparisons using multiple sequences detect three times as many remote homologues as pairwise methodsJ Mol Biol28412011210PubMedGoogle Scholar
  34. Pieterse, CM, Klooster, J, Berg-Velthuis, GC, Govers, F 1995NiaA, the structural nitrate reductase gene of Phytophthora infestans: Isolation, characterization and expression analysis in Aspergillus nidulansCurr Genet27359366PubMedGoogle Scholar
  35. Rothery, RA, Trieber, CA, Weiner, JH 1999Interactions between the molybdenum cofactor and iron-sulfur clusters of Escherichia coli dimethylsulfoxide reductaseJ Biol Chem2741300213009PubMedGoogle Scholar
  36. Saitou, N, Nei, M 1987The neighbor-joining method: A new method for reconstructing phylogenetic treesMol Biol Evol4406425PubMedGoogle Scholar
  37. Saraste, M, Castresana, J 1994Cytochrome oxidase evolved by tinkering with denitrification enzymesFEBS Lett34114PubMedGoogle Scholar
  38. Schindelin, H, Kisker, C, Hilton, J, Rajagopalan, KV, Rees, DC 1996Crystal structure of DMSO reductase: Redox-linked changes in molybdopterin coordinationScience27216151621PubMedGoogle Scholar
  39. Schneider, F, Lowe, J, Huber, R, Schindelin, H, Kisker, C, Knablein, J 1996Crystal structure of dimethyl sulfoxide reductase from Rhodobacter capsulatus at 1.88 A resolutionJ Mol Biol2635369CrossRefPubMedGoogle Scholar
  40. Stewart, LJ, Bailey, S, Bennett, B, Charnock, JM, Garner, CD, McAlpine, AS 2000Dimethylsulfoxide reductase: An enzyme capable of catalysis with either molybdenum or tungsten at the active siteJ Mol Biol299593600CrossRefPubMedGoogle Scholar
  41. Tan, J, Cowan, JA 1991Enzymatic redox chemistry: A proposed reaction pathway for the six-electron reduction of SO 3 2 − to S2− by the assimilatory-type sulfite reductase from Desulfovibrio vulgaris (Hildenborough)Biochemistry3089108917PubMedGoogle Scholar
  42. Thompson, JD, Gibson, TJ, Plewniak, F, Jeanmougin, F, Higgins, DG 1997The CLUSTAL_X windows interface: Flexible strategies for multiple sequence alignment aided by quality analysis toolsNucleic Acids Res2548764882CrossRefPubMedGoogle Scholar
  43. Trieber, CA, Rothery, RA, Weiner, JH 1996Engineering a novel iron-sulfur cluster into the catalytic subunit of Escherichia coli dimethyl-sulfoxide reductaseJ Biol Chem27146204626PubMedGoogle Scholar
  44. Unkles, SE, Campbell, EI, Punt, PJ, Hawker, KL, Contreras, R, Hawkins, AR, Hondel, CA, Kinghorn, JR 1992The Aspergillus niger niaD gene encoding nitrate reductase: Upstream nucleotide and amino acid sequence comparisonsGene111149155PubMedGoogle Scholar
  45. Vega, JM 1976A reduced pyridine nucleotides-diaphorase activity associated to the assimilatory nitrite reductase complex from Neurospora crassaArch Microbiol109237242PubMedGoogle Scholar
  46. Wieczorek, H, Brown, D, Grinstein, S, Ehrenfeld, J, Harvey, WR 1999Animal plasma membrane energization by proton-motive V-ATPasesBioessays21637648PubMedGoogle Scholar
  47. Zumft, WG, Dreusch, A, Lochelt, S, Cuypers, H, Friedrich, B, Schneider, B 1992Derived amino acid sequences of the nosZ gene (respiratory N2O reductase) from Alcaligenes eutrophus, Pseudomonas aeruginosa and Pseudomonas stutzeri reveal potential copper-binding residues. Implications for the CuA site of N2O reductase and cytochrome-c oxidaseEur J Biochem2083140PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2004

Authors and Affiliations

  1. 1.Division of Population Genetics, National Institute of Genetics, and Department of Genetics, School of Life SciencesGraduate University for Advanced StudiesMishimaJapan

Personalised recommendations