Journal of Molecular Evolution

, Volume 74, Issue 1–2, pp 1–34 | Cite as

The Phylogenomic Roots of Modern Biochemistry: Origins of Proteins, Cofactors and Protein Biosynthesis

  • Gustavo Caetano-AnollésEmail author
  • Kyung Mo Kim
  • Derek Caetano-Anollés


The complexity of modern biochemistry developed gradually on early Earth as new molecules and structures populated the emerging cellular systems. Here, we generate a historical account of the gradual discovery of primordial proteins, cofactors, and molecular functions using phylogenomic information in the sequence of 420 genomes. We focus on structural and functional annotations of the 54 most ancient protein domains. We show how primordial functions are linked to folded structures and how their interaction with cofactors expanded the functional repertoire. We also reveal protocell membranes played a crucial role in early protein evolution and show translation started with RNA and thioester cofactor-mediated aminoacylation. Our findings allow elaboration of an evolutionary model of early biochemistry that is firmly grounded in phylogenomic information and biochemical, biophysical, and structural knowledge. The model describes how primordial α-helical bundles stabilized membranes, how these were decorated by layered arrangements of β-sheets and α-helices, and how these arrangements became globular. Ancient forms of aminoacyl-tRNA synthetase (aaRS) catalytic domains and ancient non-ribosomal protein synthetase (NRPS) modules gave rise to primordial protein synthesis and the ability to generate a code for specificity in their active sites. These structures diversified producing cofactor-binding molecular switches and barrel structures. Accretion of domains and molecules gave rise to modern aaRSs, NRPS, and ribosomal ensembles, first organized around novel emerging cofactors (tRNA and carrier proteins) and then more complex cofactor structures (rRNA). The model explains how the generation of protein structures acted as scaffold for nucleic acids and resulted in crystallization of modern translation.


Aminoacyl-tRNA synthetases Non-ribosomal protein synthesis Origin of life Phylogenetic analysis Protein domain structure Ribonucleoprotein world 



Aminoacyl-tRNA synthetase


Coenzyme A




Fold superfamily


Fold family


Node distance


Peptidyl carrier protein


Ribosomal protein


Structural classification of proteins



Research was supported by the National Science Foundation (MCB-0749836), CREES-USDA, and the International Atomic Energy Agency in Vienna. Any opinions, findings, and conclusions and recommendations expressed in this material are those of the authors and do not necessarily reflect the views of the funding agencies.

Supplementary material

239_2011_9480_MOESM1_ESM.doc (1.2 mb)
Supplementary material 1 (DOC 1.21 mb)


  1. Ancel LW, Fontana W (2000) Plasticity, evolvability, and modularity in RNA. J Exp Zool (Mol Dev Evol) 288:242–283Google Scholar
  2. Andreeva A, Howorth D, Chandonia J-M, Brenner SE, Hubbard TJP, Chothia C, Murzin AG (2008) Data growth and its impact on the SCOP database: new developments. Nucleic Acids Res 36:D419–D425PubMedGoogle Scholar
  3. Aravind L, de Souza RF, Iyer LM (2010) Predicted class-I aminoacyl tRNA-synthetase-like proteins in non-ribosomal peptide synthesis. Biol Direct 5:48PubMedGoogle Scholar
  4. Artymiuk PJ, Rice DW, Poirrette AR, Willet P (1994) A tale of two synthetases. Nat Struct Biol 1:758–760PubMedGoogle Scholar
  5. Ashkenasy G, Jagasia R, Yadav M, Ghadiri MR (2004) Design of a directed molecular network. Proc Natl Acad Sci USA 101:10872–10877PubMedGoogle Scholar
  6. Babajide A, Farber R, Hofacker IL, Inman J, Lapedes AS, Stadler PF (2001) Exploring protein sequence space using knowledge based potentials. J Theor Biol 212:35–46PubMedGoogle Scholar
  7. Banavar JR, Maritan A (2007) Physics of proteins. Annu Rev Biophys Biomol Struct 36:261–280PubMedGoogle Scholar
  8. Bar-Tana J, Rose G (1968) Studies on medium-chain fatty acyl-coenzyme A synthetase. Enzyme fraction I: mechanism of reaction and allosteric properties. Biochem J 109:275–282PubMedGoogle Scholar
  9. Bashton M, Nobeli I, Thornton JM (2008) PROCOGNATE: a cognate ligand domain mapping for enzymes. Nucleic Acids Res 36:D618–D622PubMedGoogle Scholar
  10. Bork P, Holm L, Koonin EV, Sander C (1995) The cytidylyltransferase superfamily: identification of the nucleotide-binding site and fold prediction. Proteins 22:259–266PubMedGoogle Scholar
  11. Caetano-Anollés G, Caetano-Anollés D (2003) An evolutionarily structured universe of protein architecture. Genome Res 13:1563–1571PubMedGoogle Scholar
  12. Caetano-Anollés G, Mittenthal JE (2010) Exploring the interplay of stability and function in protein evolution. Bioessays 32:655–658PubMedGoogle Scholar
  13. Caetano-Anollés G, Kim HS, Mittenthal JE (2007) The origin of modern metabolic networks inferred from phylogenomic analysis of protein architecture. Proc Natl Acad Sci USA 104:9358–9363PubMedGoogle Scholar
  14. Caetano-Anollés G, Wang M, Caetano-Anollés D, Mittenthal JE (2009a) The origin, evolution and structure of the protein world. Biochem J 417:621–637PubMedGoogle Scholar
  15. Caetano-Anollés G, Yafremava LS, Gee H, Caetano-Anollés D, Kim HS, Mittenthal JE (2009b) The origin and evolution of modern metabolism. Intl J Biochem Cell Biol 41:285–297Google Scholar
  16. Caetano-Anollés D, Kim KM, Mittenthal JE, Caetano-Anollés G (2011) Proteome evolution and metabolic origins of translation and cellular life. J Mol Evol 72:14–33PubMedGoogle Scholar
  17. Cate JH, Yusupov MM, Yusupova GZ, Earnest TN, Noller HF (1999) X-ray crystal structures of 70S ribosome functional complexes. Science 285:2095–2104PubMedGoogle Scholar
  18. Chan DI, Vogel HJ (2010) Current understanding of fatty acid biosynthesis and the acyl carrier protein. Biochem J 430:1–19PubMedGoogle Scholar
  19. Chen IA, Roberts RW, Szostak JW (2004) The emergence of competition between model protocells. Science 305:1474–1476PubMedGoogle Scholar
  20. Chothia C (1973) Conformation of twisted β-sheets in proteins. J Mol Biol 75:295–302PubMedGoogle Scholar
  21. Chothia C, Gough J (2009) Genomic and structural aspects of protein evolution. Biochem J 419:15–28PubMedGoogle Scholar
  22. Cleland WW (1963) The kinetics of enzyme-catalyzed reactions with two or more substrates or products. I. Nomenclature and rate equations. Biochim Bophys Acta 67:104–137Google Scholar
  23. Cossio P, Trovato A, Pietrucci F, Seno F, Maritan A, Laio A (2010) Exploring the universe of protein structures beyond the Protein Data Bank. PLoS Comput Biol 6:e1000957PubMedGoogle Scholar
  24. Cothia C, Lesk M (1986) The relation between the divergence of sequence and structure in proteins. EMBO J 5:823–826Google Scholar
  25. Cramer F, Englisch U, Freist W, Sternbach H (1991) Aminoacylation of tRNA as critical step in protein biosynthesis. Biochimie 73:1027–1035PubMedGoogle Scholar
  26. Danchin A, Fang G, Noria S (2007) The extant core bacterial proteome is an archive of the origin of life. Proteomics 7:875–889PubMedGoogle Scholar
  27. Deamer DW (1997) The first living systems: a bioenergetic perspective. Microbiol Mol Biol Rev 61:239–261PubMedGoogle Scholar
  28. Denessiouk KA, Rantanen V-V, Johnson MJ (2001) Adenine recognition: A motif present in ATP-, CoA-, NAD-, NADP-, and FAD-dependent proteins. Proteins 44:282–291PubMedGoogle Scholar
  29. Di Giulio M (2006) The non-monophyletic origin of the tRNA molecule and the origin of genes only after the evolutionary stage of the last universal common ancestor (LUCA). J Theor Biol 240:343–352PubMedGoogle Scholar
  30. Di Giulio M (2009) Formal proof that the split genes of tRNA of Nanoarchaeum equitans are an ancestral character. J Mol Evol 69:505–511PubMedGoogle Scholar
  31. Dieckmann R, Pavela-Vrancic M, von Döhren H (2001) Synthesis of (di)adenosine polyphosphates by non-ribosomal peptide synthetases. Biochim Biophys Acta 1546:234–241PubMedGoogle Scholar
  32. Dill KA, Ozkan SB, Shell MS, Weiki TR (2008) The protein folding problem. Annu Rev Biophys 37:289–316PubMedGoogle Scholar
  33. Domazet-Laso T, Tautz D (2010) A phylogenetically based transcriptome age index mirrors ontogenetic divergence patterns. Nature 468:815–818Google Scholar
  34. Duax WL, Huether R, Pletnev V, Langs D, Addlagatta A, Connare S, Habegger L, Gill J (2005) Rational genomics I. Antisense open reading frames and codon bias in short oxidoreductase enzymes and the evolution of the genetic code. Proteins 61:900–906PubMedGoogle Scholar
  35. Duax WL, Huether R, Pletnev V, Umland TC, Weeks CM (2009) Divergent evolution of a Rossmann fold and identification of its oldest surviving ancestor. Int J Bioinform Res Appl 5:280–294PubMedGoogle Scholar
  36. Dupont CL, Butcher A, Valas RE, Bourne PE, Caetano-Anollés G (2010) History of biological metal utilization inferred through phylogenomic analysis of protein structure. Proc Natl Acad Sci USA 107:10567–10572PubMedGoogle Scholar
  37. Dwyer MA, Hellinga HW (2004) Periplasmic binding proteins: a versatile superfamily for protein engineering. Curr Opin Struct Biol 14:495–504PubMedGoogle Scholar
  38. Dyson FJ (1982) A model for the origin of life. J Mol Evol 18:344–350PubMedGoogle Scholar
  39. Ellington AD, Chen X, Robertson M, Syrett A (2009) Evolutionary origins and directed evolution of RNA. Intl J Biochem Cell Biol 41:254–265Google Scholar
  40. Engel MH, Macko SA (1997) Isotopic evidence for extraterrestrial non-racemic amino acids in the Murchison meteorite. Nature 389:265–268PubMedGoogle Scholar
  41. Engelman DM, Chen Y, Chin C-N, Curran R, Dixon AM, Dupuy AD, Lee AS, Lehnert U, Mathews EE, Reshetnyak YK, Senes A, Popot J-L (2003) Membrane protein folding: beyond the two stage model. FEBS Lett 555:122–125PubMedGoogle Scholar
  42. Eriani G, Delarue M, Poch O, Gangloff J, Moras D (1990) Partition of tRNA synthetases into two classes based on mutually exclusive sets of sequence motifs. Nature 347:203–206PubMedGoogle Scholar
  43. Finking R, Marahiel MA (2004) Biosynthesis of nonribosomal peptides. Annu Rev Microbiol 58:453–488PubMedGoogle Scholar
  44. Fischer JD, Holliday GL, Thornton JM (2010) The CoFactor database: organic cofactors in enzyme catalysis. Bioinformatics 26:2496–2497PubMedGoogle Scholar
  45. Flores SC, Gerstein MB (2007) FlexOracle: predicting flexible hinges by identification of stable domains. BMC Bioinform 8:215Google Scholar
  46. Flores S, Echols N, Milburn D, Hespenheide B, Keating K, Lu J, Wells S, Yu EZ, Thorpe M, Gerstein M (2006) The database of macromolecular motions: new features added at the decade mark. Nucleic Acids Res 34:D296–D301PubMedGoogle Scholar
  47. Fontana W (2002) Modeling ‘evo-devo’ with RNA. Bioessays 24:1164–1177PubMedGoogle Scholar
  48. Forslund K, Henricson A, Hollich V, Sonnhammer ELL (2007) Domain tree-based analysis of protein architecture evolution. Mol Biol Evol 25:254–264PubMedGoogle Scholar
  49. Fox SW (1980) Metabolic microspheres. Naturwissenschaften 67:378–383PubMedGoogle Scholar
  50. Francklyn CS, Minajigi A (2010) tRNA as active chemical scaffold for diverse chemical transformations. FEBS Lett 584:366–375PubMedGoogle Scholar
  51. Garg RP, Qian XL, Alemany LB, Moran S, Parry RJ (2008) Investigations of valanimycin biosynthesis: elucidation of the role of seryl-tRNA. Proc Natl Acad Sci USA 105:6543–6547PubMedGoogle Scholar
  52. Gaucher EA, Thomson JM, Burgan MF, Benner SA (2003) Inferring the palaeoenvironment of ancient bacteria on the basis of resurrected proteins. Nature 425:285–288PubMedGoogle Scholar
  53. Gerstein M (1998) Patterns of protein-fold usage in eight microbial genomes: a comprehensive structural census. Proteins 33:518–534PubMedGoogle Scholar
  54. Gerstein M, Levitt M (1997) A structural census of the current population of protein sequences. Proc Natl Acad Sci USA 94:11911–11916PubMedGoogle Scholar
  55. Goerlich O, Foeckler R, Holler L (1982) Mechanism of synthesis of adenosine(5′)tetraphospho(5′)adenosine (AppppA) by aminoacyl-tRNA synthetases. Eur J Biochem 126:135–142PubMedGoogle Scholar
  56. Gondry M, Sauguet L, Belin P, Thai R, Amouroux R, Tellier C, Tuphile K, Jacquet M, Braud S, Courçon M, Masson C, Dubois S, Lautru S, Lecoq A, Hishimoto S, Genet R, Pernodet J-L (2009) Cyclodipeptide synthases are a family of tRNA-dependent peptide bond-forming enzymes. Nat Chem Biol 5:414–420PubMedGoogle Scholar
  57. Gough J, Karplus K, Hughey R, Chothia C (2001) Assignment of homology to genome sequences using a library of Hidden Markov Models that represent all proteins of known structure. J Mol Biol 313:903–919PubMedGoogle Scholar
  58. Greene LH, Lewis TE, Addou S, Cuff A, Dallman T, Dibley M, Redfern O, Pearl F, Nambudiry R, Reid A, Sillitoe I, Yeats C, Thornton JM, Orengo CA (2007) The CATH domain structure database: new protocols and classification levels give a more comprehensive resource for exploring evolution. Nucleic Acids Res 35:D291–D297PubMedGoogle Scholar
  59. Gregory ST, Carr JF, Dahlberg AE (2009) A signal relay between ribosomal protein S12 and elongation factor EF-Tu during decoding of mRNA. RNA 15:208–214PubMedGoogle Scholar
  60. Guerler A, Knapp E-W (2008) Novel protein folds and their non-sequential structural analogs. Protein Sci 17:1374–1382PubMedGoogle Scholar
  61. Gulick AM (2009) Conformational dynamics in the acyl-CoA synthetases, adenylation domains of the non-ribosomal peptide synthetases, and firefly luciferase. ACS Chem Biol 4:811–827PubMedGoogle Scholar
  62. Guo M, Yang X-L, Schimmel P (2010) New functions of aminoacyl-tRNA synthetases beyond translation. Nat Rev 11:668–674Google Scholar
  63. Haapalainen AM, Meriläinen G, Wierenga RK (2006) The thiolase superfamily: condensing enzymes with diverse reaction specificities. Trends Biochem Sci 31:64–71PubMedGoogle Scholar
  64. Hanczyc MM, Fujikawa SM, Szostak JW (2003) Experimental models of primitive cellular compartments: encapsulation, growth, and division. Science 302:618–622PubMedGoogle Scholar
  65. Harish A, Caetano-Anollés G (2011) Ribosomal history reveals origins of modern protein synthesis. Ms. submittedGoogle Scholar
  66. Hattendorf DA, Lindquist SL (2002) Cooperative kinetics of both Hsp104 ATPase domains and interdomain communication revealed by AAA sensor-1 mutants. EMBO J 21:12–21PubMedGoogle Scholar
  67. Hausmann CD, Ibba M (2008) Structural and functional mapping of the archaeal multi-aminoacyl-tRNA synthetase complex. FEBS Lett 582:2178–2182PubMedGoogle Scholar
  68. Hausmann CD, Praetorius-Ibba M, Ibba M (2007) An aminoacyl-tRNA synthetase: elongation factor complex for substrate channeling in archaeal translation. Nucleic Acids Res 35:6094–6102PubMedGoogle Scholar
  69. Higgins CF (1992) ABC transporters: from microorganisms to man. Annu Rev Cell Biol 8:67–113PubMedGoogle Scholar
  70. Hinnerwisch J, Fenton WA, Furtak KJ, Farr GW, Horwich AL (2005) Loops in the central channel of ClpA chaperone mediate protein binding, unfolding, and translocation. Cell 121:1029–1041PubMedGoogle Scholar
  71. Hoang TX, Trovato A, Seno F, Banavar JR, Maritan A (2004) Geometry and symmetry presculpt the free-energy landscape of proteins. Proc Natl Acad Sci USA 101:7960–7964PubMedGoogle Scholar
  72. Holland T, Veretnik S, Shindyalov I, Bourne P (2006) Partitioning protein structures into domains: Why is it so difficult? J Mol Biol 361:562–590PubMedGoogle Scholar
  73. Huber C, Wächtershäuser G (1998) Peptides by activation of amino acids on (Fe, Ni)S surfaces: implications for the origin of life. Science 281:670–672PubMedGoogle Scholar
  74. Hung L-W, Wang IX, Nikaido K, Liu P-Q, Ferro-Luzzi Ames G, Kim S-H (1998) Crystal structure of a ATP-binding subunit of an ANC transporter. Nature 396:703–707PubMedGoogle Scholar
  75. Hurley JH (1996) The sugar kinase/heat shock protein/actin superfamily. Annu Rev Biophys Biomol Struct 25:137–162PubMedGoogle Scholar
  76. Illergård K, Ardell DH, Elofsson A (2009) Structure is three to ten times more conserved than sequence—a study of structural response in protein cores. Proteins 77:499–508PubMedGoogle Scholar
  77. Iyer LM, Leipe DD, Koonin EV, Aravind L (2004) The evolutionary history and higher order classification of AAA+ ATPases. J Struct Biol 146:11–31PubMedGoogle Scholar
  78. Iyer LM, Abhiman S, Maxwell Burroughs A, Aravind L (2009) Amidoligases with ATP-grasp, glutamine synthetase-like and acetyltransferase-like domains: synthesis of novel metabolites and peptide modifications of proteins. Mol Biosyst 5:1636–1660PubMedGoogle Scholar
  79. Izard T (2003) Novel adenylate binding site confers phophopantetheine adenylyltransferase interactions with coenzyme A. J Bacteriol 185:4074–4080PubMedGoogle Scholar
  80. Jakubowski H (1997) Aminoacyl thioester chemistry of class II aminoacyl-tRNA synthetases. Biochemistry 36:11077–11085PubMedGoogle Scholar
  81. Jakubowski H (1998) Aminoacylation of coenzyme A and pantetheine by aminoacyl-tRNA synthetases: possible link between noncoded and coded peptide synthesis. Biochemistry 37:5147–5153PubMedGoogle Scholar
  82. Jakubowski H (2000) Amino acid selectivity in the aminoacylation of coenzyme A and RNA minihelices by aminoacyl-tRNA synthetases. J Biol Chem 275:34845–34848PubMedGoogle Scholar
  83. Jensen RA (1976) Enzyme recruitment in evolution of new function. Annu Rev Microbiol 30:409–425PubMedGoogle Scholar
  84. Jermann TM, Opitz JG, Stackhouse J, Benner SA (1995) Reconstructing the evolutionary history of the artiodactyl ribonuclease superfamily. Nature 374:57–59PubMedGoogle Scholar
  85. Ji HF, Kong DX, Shen L, Chen LL, Ma BG, Zhang HY (2007) Distribution patterns of small molecule ligands in the protein universe and implications for origins of life and drug discovery. Genome Biol 8:R176PubMedGoogle Scholar
  86. Kacser H, Beeby R (1984) On the origin of enzyme species by means of natural selection. J Mol Evol 20:38–51PubMedGoogle Scholar
  87. Kamioka S, Ajami D, Rebek J Jr (2010) Autocatalysis and organocatalysis with synthetic structures. Proc Natl Acad Sci USA 107:541–544PubMedGoogle Scholar
  88. Kauffmann SA (1986) Autocatalytic sets of proteins. J Theor Biol 119:1–24Google Scholar
  89. Kauffmann SA (1993) The origins of order. Oxford University Press, New YorkGoogle Scholar
  90. Kauffmann SA (2007) Question 1: origin of life and the living state. Orig Life Evol Biosph 37:315–322Google Scholar
  91. Kavanagh KL, Jörnvall H, Persson B, Oppermann U (2008) The SDR superfamily: functional and structural diversity within a family of metabolic and regulatory enzymes. Cell Mol Life Sci 65:3895–3906PubMedGoogle Scholar
  92. Keefe AD, Szostak JW (2001) Functional proteins from a random-sequence library. Nature 410:715–718PubMedGoogle Scholar
  93. Kim KM, Caetano-Anollés G (2010) Emergence and evolution of modern molecular functions inferred from phylogenomic analysis of ontological data. Mol Biol Evol 27:1710–1733PubMedGoogle Scholar
  94. Kim KM, Caetano-Anollés G (2011) The proteomic complexity and rise of the primordial ancestor of diversified life. BMC Evol Biol 11:140PubMedGoogle Scholar
  95. Kim HS, Mittenthal JE, Caetano-Anollés G (2006) MANET: tracing evolution of protein architecture in metabolic networks. BMC Bioinform 7:351Google Scholar
  96. Kisselev LL, Justesen J, Wolfson AD, Frolova LY (1998) Diadenosine oligophosphates (ApnA), a novel class of signaling molecules? FEBS Lett 427:157–163PubMedGoogle Scholar
  97. Koglin A, Walsh CT (2009) Structural insights into ribosomal peptide enzymatic assembly lines. Nat Prod Rep 26:987–1000PubMedGoogle Scholar
  98. Koglin A, Mofid MR, Löhr F, Schäfer B, Rogov VV, Blum M-M, Mittag T, Marahiel MA, Bernhard F, Dötsch V (2006) Conformational switches modulate protein interactions in peptide antibiotic synthetases. Science 312:273–276PubMedGoogle Scholar
  99. Kramer G, Boehringer D, Ban N, Bukau B (2010) The ribosome as a platform for co-translational processing, folding and targeting of newly synthesized proteins. Nat Struct Mol Biol 16:589–597Google Scholar
  100. Krishna SS, Grishin NV (2004) Structurally analogous proteins do exist! Structure 12:1125–1127PubMedGoogle Scholar
  101. Kurland CG (2010) The RNA dreamtime. Bioessays 32:866–871PubMedGoogle Scholar
  102. LaBean TH, Butt TR, Kauffman SA, Schultes EA (2011) Protein folding absent selection. Genes 2:608–626Google Scholar
  103. Lazcano A (2010) Which way to life? Orig Life Evol Biosph 40:161–167PubMedGoogle Scholar
  104. Laskowski RA (2009) PDBsum new things. Nucleic Acids Res 37:D355–D359PubMedGoogle Scholar
  105. Lee DH, Granja JR, Martinez JA, Severin K, Ghadiri MR (1996) A self-replicating peptide. Nature 382:525–528PubMedGoogle Scholar
  106. Lee SW, Cho BH, Park SG, Kim S (2004) Aminoacyl-tRNA synthetase complexes: Beyond translation. J Cell Sci 117:3725–3734PubMedGoogle Scholar
  107. Leibniz GW (1923) Sämtliche Schrifen un Briefe, Deutsche Akademie der Wissenschaften. Akademie Verlag, DarmstadtGoogle Scholar
  108. Levitt M (2009) Nature of the protein universe. Proc Natl Acad Sci USA 106:11079–11084PubMedGoogle Scholar
  109. Lin J, Gerstein M (2000) Whole-genome trees based on the occurrence of folds and orthologs: implications for comparing genomes on different levels. Genome Res 10:808–818PubMedGoogle Scholar
  110. Lincoln TA, Joyce GF (2009) Self-sustained replication of an RNA enzyme. Science 323:1229–1232PubMedGoogle Scholar
  111. Ling J, Roy H, Ibba M (2007) Mechanism of tRNA-dependent editing in translational quality control. Proc Natl Acad Sci USA 104:72–77PubMedGoogle Scholar
  112. Linton KJ, Higgins CF (2001) Structure and function of ABC transporters: the ATP switch provides flexible control. Eur J Physiol 453:555–567Google Scholar
  113. Lipmann F (1971) Attempts to map a process evolution of peptide biosynthesis. Science 173:875–884PubMedGoogle Scholar
  114. Lo Surdo P, Walsh MA, Sollazzo M (2004) A novel ADP- and zinc-binding fold from function-directed in vitro evolution. Nat Struct Mol Biol 11:382–383PubMedGoogle Scholar
  115. Locher KP (2009) Structure and mechanism of ATP-binding cassette transporters. Philos Trans R Soc B 364:239–245Google Scholar
  116. Lupas A, Matin J (2002) AAA proteins. Curr Opin Struct Biol 12:746–753PubMedGoogle Scholar
  117. MacKenzie KR, Fleming KG (2007) Association energetics of membrane spanning α-helices. Curr Opin Struct Biol 18:412–419Google Scholar
  118. Mansy SS, Schrum JP, Krishnamurthy M, Tobe S, Treco DA, Szostak JW (2008) Replication of a genetic polymer inside of a model protocell. Nature 454:122–125PubMedGoogle Scholar
  119. Marahiel MA (2009) Working outside the protein-synthesis rules: insights into non-ribosomal peptide synthesis. J Pept Sci 15:799–807PubMedGoogle Scholar
  120. Martin W, Russell MJ (2007) On the origin of biochemistry at an alkaline hydrothermal vent. Philos Trans R Soc B 362:1887–1925Google Scholar
  121. Martinez MA, Pezo V, Marlére P, Wain-Hobson S (1997) Exploring the functional robustness of an enzyme by in vitro evolution. EMBO J 15:1203–1210Google Scholar
  122. McElroy WD, DeLuca M, Travis J (1967) Molecular uniformity in biological catalyses. The enzymes concerned with firefly luciferin, amino acid, and fatty acid utilization are compared. Science 157:150–160PubMedGoogle Scholar
  123. Milner-White EJ, Russell MJ (2008) Predicting the conformations of peptides and proteins in early evolution. A review article submitted to Biology Direct. Biol Direct 3:3PubMedGoogle Scholar
  124. Milner-White EJ, Nissink JWM, Allen FH, Duddy WJ (2004) Recurring main-chain anion-binding motifs in short polypeptides: nests. Acta Cryst D60:1935–1942Google Scholar
  125. Minajigi A, Francklyn CS (2008) RNA-assisted catalysis in a protein enzyme: the 20-hydroxyl of tRNA(Thr) A76 promotes aminoacylation by threonyl-tRNA synthetase. Proc Natl Acad Sci USA 105:17748–17753PubMedGoogle Scholar
  126. Mocibob M, Ivic N, Bilokapic S, Maier T, Luic M, Ban N, Weygand-Durasevic I (2010) Homologs of aminoacyl-tRNA synthetases acylate carrier proteins and provide a link between ribosomal and nonribosomal peptide synthesis. Proc Natl Acad Sci USA 107:14585–14590PubMedGoogle Scholar
  127. Morowitz HJ (1999) A theory of biochemical organization, metabolic pathways, and evolution. Complexity 4:39–53Google Scholar
  128. Morris CE (2002) How did cells get their size? Anat Rec 268:239–251PubMedGoogle Scholar
  129. Murzin AG, Lesk AM, Chothia C (1994a) Principles determining the structure of β-sheet barrels in proteins. I. A theoretical analysis. J Mol Biol 236:1369–1381PubMedGoogle Scholar
  130. Murzin AG, Lesk AM, Chothia C (1994b) Principles determining the structure of β-sheet barrels in proteins. II. The observed structures. J Mol Biol 236:1382–1400PubMedGoogle Scholar
  131. Murzin AG, Brenner SE, Hubbard TH, Chothia C (1995) SCOP: the structural classification of proteins database. J Mol Biol 247:536–540PubMedGoogle Scholar
  132. Nakamura Y, Ito K (2003) Making sense of mimic in translation termination. Trends Biochem Sci 28:99–103PubMedGoogle Scholar
  133. Nixon KC (1999) The parsimony ratchet, a new method for rapid parsimony analysis. Cladistics 15:407–414Google Scholar
  134. O’Reilly AO, Wallace BA (2003) The peptaibol antiamoebin as a model ion channel: Similarities to bacterial potassium channels. J Pept Sci 9:769–775PubMedGoogle Scholar
  135. Onuchic JN, Wolynes PG (2004) Theory of protein folding. Curr Opin Struct Biol 14:70–75PubMedGoogle Scholar
  136. Orgel LE (2008) The implausibility of metabolic cycles on the prebiotic Earth. PLoS Biol 6:e18PubMedGoogle Scholar
  137. Ortlund EA, Bridgham JT, Redinbo MR, Thornton JW (2007) Crystal structure of an ancient protein: evolution by conformational epistasis. Science 317:1544–1548PubMedGoogle Scholar
  138. Pak M, Hoskins JR, Singh SK, Maurizi MR, Wickner S (1999) Concurrent chaperone and protease activities of ClpAP and the requirement for the N-terminal ClpA ATP binding site for chaperone activity. J Biol Chem 274:19316–19322PubMedGoogle Scholar
  139. Paula S, Volkov AG, Van Hoek AN, Haines TH, Deamer DW (1996) Permeation of protons, potassium ions, and small polar molecules through phospholipid bilayers as a function of membrane thickness. Biophys J 70:339–348PubMedGoogle Scholar
  140. Pffeifer T, Soyer OS, Bonhoeffer S (2005) The evolution of connectivity in metabolic networks. PLoS Biol 3:1269–1275Google Scholar
  141. Pham Y, Li L, Erdogan O, Weinreb V, Butterfoss GL, Kuhlman B, Carter CW Jr (2007) A minimal TrpRS catalytic domain supports sense/antisense ancestry of class I and II aminoacyl-tRNA synthetases. Mol Cell 25:851–862PubMedGoogle Scholar
  142. Pohorille A, Deamer DW (2009) Self-assembly and function of primitive cell membranes. Res Microbiol 160:449–456PubMedGoogle Scholar
  143. Pohorille A, Scheweighofer K, Wilson MA (2005) The origin and early evolution of membrane channels. Astrobiology 5:1–17PubMedGoogle Scholar
  144. Popot JL, Engelman DM (1990) Membrane protein folding and oligomerization: the two-stage model. Biochemistry 29:4031–4037PubMedGoogle Scholar
  145. Popot JL, Engelman DM (2000) Helical membrane protein folding, stability, and evolution. Annu Rev Biochem 69:881–922PubMedGoogle Scholar
  146. Powner MW, Gerland B, Sutherland JD (2009) Synthesis of activated pyrimidine ribonucleotides in prebiotically plausible conditions. Nature 459:239–242PubMedGoogle Scholar
  147. Praetorius-Ibba M, Hausmann CD, Paras M, Rogers TE, Ibba M (2007) Functional association between three archaeal aminoacyl-tRNA synthetases. J Biol Chem 282:3680–3687PubMedGoogle Scholar
  148. Remmert M, Biegert A, Linke D, Lupas AN, Söding J (2010) Evolution of outer membrane β-barrels from an ancestral ββ hairpin. Mol Biol Evol 27:1348–1358PubMedGoogle Scholar
  149. Renthal R (2010) Helix insertion into bilayers and the evolution of membrane proteins. Cell Mol Life Sci 67:1077–1088PubMedGoogle Scholar
  150. Ribas de Pouplana L, Schimmel P (2001a) Aminoacyl-tRNA synthetases: potential markers of genetic code development. Trends Biochem Sci 26:591–595PubMedGoogle Scholar
  151. Ribas de Pouplana L, Schimmel P (2001b) Two classes of tRNA synthetases suggested by sterically compatible dockings on tRNA acceptor stem. Cell 104:191–193PubMedGoogle Scholar
  152. Robertson MP, Scott WG (2007) The structural basis of ribozyme-catalyzed RNA assembly. Science 315:1549–1553PubMedGoogle Scholar
  153. Robinson JC, Kerjan P, Mirande M (2000) Macromolecular assemblage of aminoacyl-tRNA synthetases: quantitative analysis of protein-protein interactions and mechanism of complex assembly. J Mol Biol 304:983–994PubMedGoogle Scholar
  154. Rode BM (1999) Peptides and the origin of life. Peptides 20:773–786PubMedGoogle Scholar
  155. Rode BM (2007) The first steps of chemical evolution towards the origin of life. Chem Biodivers 4:2674–2702PubMedGoogle Scholar
  156. Rodin SN, Ohno S (1995) Two types of aminoacyl-tRNA synthetases could be originally encoded by complementary strands of the same nucleic acid. Orig Life Evol Biosph 25:565–589PubMedGoogle Scholar
  157. Rodin SN, Rodin AS (2008) On the origin of the genetic code: signatures of its primordial complementarity in tRNAs and aminoacyl-tRNA synthetases. Heredity 100:341–355PubMedGoogle Scholar
  158. Rodin AS, Szathmary E, Rodin SN (2009) One ancestor for two codes viewed from the perspective of two complementary modes of tRNA aminoacylation. Biol Direct 4:4PubMedGoogle Scholar
  159. Rodnina MV, Wintermeyer W (2009) Recent mechanistic insights into eukaryotic ribosomes. Curr Opin Cell Biol 21:435–443PubMedGoogle Scholar
  160. Saier MH Jr (2003) Tracing pathways of transport protein evolution. Mol Microbiol 48:1145–1156PubMedGoogle Scholar
  161. Saier MH Jr, Yen MR, Noto K, Tamang DG, Elkan C (2009) The Transporter Classification Database: recent advances. Nucleic Acids Res 37:D274–D278PubMedGoogle Scholar
  162. Seelig B, Szostak JW (2007) Selection and evolution of enzymes from a partially randomized non-catalytic scaffold. Nature 448:828–831PubMedGoogle Scholar
  163. Severin K, Lee DH, Kennan AJ, Ghadiri MR (1997) A synthetic peptide ligase. Nature 389:706–709PubMedGoogle Scholar
  164. Smith MD, Rosenow MA, Wang M, Allen JP, Szostak JW, Chaput JC (2007) Structural insights into the evolution of a non-biological protein: importance of surface residues in protein fold optimization. PLoS ONE 2(5):e467PubMedGoogle Scholar
  165. Stachelhaus T, Mootz HD, Marahiel MA (1999) The specificity-conferring code of adenylation domains in non-ribosomal peptide synthetases. Chem Biol 6:493–505PubMedGoogle Scholar
  166. Sterner R, Höcker B (2005) Catalytic versatility, stability, and evolution of the (βα)8-barrel enzyme fold. Chem Rev 105:4038–4055PubMedGoogle Scholar
  167. Stomel JM, Wilson JW, León MA, Stafford P, Chaput JC (2009) A man-made ATP-binding protein evolved independent of nature causes abnormal growth in bacterial cells. PLoS ONE 4(10):e7385PubMedGoogle Scholar
  168. Sun F-J, Caetano-Anollés G (2008a) Evolutionary patterns in the sequence and structure of transfer RNA: a window into early translation and the genetic code. PLoS ONE 3:e2799PubMedGoogle Scholar
  169. Sun F-J, Caetano-Anollés G (2008b) The origin and evolution of tRNA inferred from phylogenetic analysis of structure. J Mol Evol 66:21–35PubMedGoogle Scholar
  170. Sun F-J, Caetano-Anollés G (2009) The evolutionary history of the structure of 5S ribosomal RNA. J Mol Evol 69:430–443PubMedGoogle Scholar
  171. Sun F-J, Caetano-Anollés G (2010) The ancient history of the structure of ribonuclease P and the early origins of Archaea. BMC Bioinform 11:153Google Scholar
  172. Swofford DL (2002) Phylogenetic analysis using parsimony and other programs (PAUP*). Ver 4.0b10. Sinauer, SunderlandGoogle Scholar
  173. Tam R, Saier MH Jr (1993) Structural, functional, and evolutionary relationships among extracellular solute-binding receptors of bacteria. Microbiol Rev 57:320–346PubMedGoogle Scholar
  174. Tanovic A, Samel SA, Essen LO, Marahiel MA (2008) Crystal structure of the termination module of a nonribosomal peptide synthetase. Science 322:659–663Google Scholar
  175. Taylor WR (2002) A ‘periodic table’ for protein structures. Nature 416:657–660PubMedGoogle Scholar
  176. Taylor WR (2007) Evolutionary transitions of protein fold space. Curr Opin Struct Biol 17:354–361PubMedGoogle Scholar
  177. Teichmann SA, Rison SCG, Thornton JM, Riley M, Gough J, Chothia C (2001) Small-molecule metabolism: an enzyme mosaic. Trends Biotechnol 19:482–486PubMedGoogle Scholar
  178. Terada T, Nureki O, Ishitani R, Ambrogelly A, Ibba M, Söll D, Yokohama S (2002) Functional convergence of two lysyl-tRNA synthetases with unrelated topologies. Nat Struct Biol 9:257–262PubMedGoogle Scholar
  179. Ungermann C, Nichols BJ, Pelham HR, Wickner W (1998) A vacuolar v-t-SNARE complex, the predominant form in vivo and on isolated vacuoles, is disassembled and activated for docking and fusion. J Cell Biol 140:61–69PubMedGoogle Scholar
  180. Vale RD (2000) AAA proteins: lords of the ring. J Cell Biol 150:F13–F19PubMedGoogle Scholar
  181. Vauthey S, Santoso S, Gong H, Watson N, Zhang S (2002) Molecular self-assembly of surfactant-like peptides to form nanotubes and nanovesicles. Proc Natl Acad Sci USA 99:5355–5360PubMedGoogle Scholar
  182. Vetting MW, Hedge SS, Blanchard JS (2010) The structure and mechanism of the Mycobacterium tuberculosis cyclodityrosine synthetase. Nat Chem Biol 6:797–799PubMedGoogle Scholar
  183. Vidonne A, Philp D (2009) Making molecules make themselves—the chemistry of artificial replicators. Eur J Org Chem 5:593–610Google Scholar
  184. Vlassov A, Khvorova A, Yarus M (2001) Binding and disruption of phospholipid bilayers by supramolecular RNA complexes. Proc Natl Acad Sci USA 98:7706–7711PubMedGoogle Scholar
  185. Von Delft F, Lewendon A, Dhanaraj V, Blundell TL, Abell C, Smith AG (2001) The crystal structure of E. coli pantothenate synthetase confirms it as a member of the cytidyltransferase superfamily. Structure 9:439–450Google Scholar
  186. Wallin E, von Heijne G (1998) Genome-wide analysis of integral membrane proteins from eubacterial, archaean, and eukaryotic organisms. Protein Sci 7:1029–1038PubMedGoogle Scholar
  187. Wang M, Caetano-Anollés G (2006) Global phylogeny determined by the combination of protein domains in proteomes. Mol Biol Evol 23:2444–2454PubMedGoogle Scholar
  188. Wang M, Caetano-Anollés G (2009) The evolutionary mechanics of domain organization in proteomes and the rise of modularity in the protein world. Structure 17:66–78PubMedGoogle Scholar
  189. Wang M, Boca SM, Kalelkar R, Mittenthal JE, Caetano-Anollés G (2006) A phylogenomic reconstruction of the protein world based on a genomic census of protein fold architecture. Complexity 12:27–40Google Scholar
  190. Wang M, Yafremava LS, Caetano-Anolles D, Mittenthal JE, Caetano-Anolles G (2007) Reductive evolution of architectural repertoires in proteomes and the birth of the tripartite world. Genome Res 17:1572–1585PubMedGoogle Scholar
  191. Wang M, Jiang Y-Y, Kim KM, Qu G, Ji HF, Mittenthal JE, Zhang H-Y, Caetano-Anollés G (2011) A universal molecular clock of protein folds and its power in tracing the early history of aerobic metabolism and planet oxygenation. Mol Biol Evol 28:567–582PubMedGoogle Scholar
  192. Watson JD, Milner-White EJ (2002) A novel main-chain anion-binding site in proteins: the nest. A particular combination of ϕ, ψ values in successive residues gives rise to anion-binding sites that occur commonly and are found often at functionally important regions. J Mol Biol 315:171–182PubMedGoogle Scholar
  193. Weinger JS, Parnell KM, Dorner S, Green R, Strobel SA (2004) Substrate-assisted catalysis of peptide bond formation by the ribosome. Nat Struct Mol Biol 11:1101–1106PubMedGoogle Scholar
  194. White SR, Lauring B (2007) AAA+ ATPases: achieving diversity of function with conserved machinery. Traffic 8:1657–1667PubMedGoogle Scholar
  195. White SH, von Heijne G (2005) Transmembrane helices before, during, and after insertion. Curr Opin Struct Biol 15:378–386PubMedGoogle Scholar
  196. Widmann J, Di Giulio M, Yarus M, Knight R (2005) tRNA creation by hairpin duplication. J Mol Evol 61:524–530PubMedGoogle Scholar
  197. Wilson D, Pethica R, Zhou Y, Talbot C, Vogel C, Madera M, Chothia C, Gough J (2009) SUPERFAMILY—sophisticated comparative genomics, data mining, visualization and phylogeny. Nucleic Acids Res 37:D380–D386PubMedGoogle Scholar
  198. Yang S, Doolittle RF, Bourne PE (2005) Phylogeny determined based on protein domain content. Proc Natl Acad Sci USA 102:373–378PubMedGoogle Scholar
  199. Yarus M (2010) Getting pass the RNA world: the initial Darwinian ancestor. Cold Spring Harb Perspect Biol 1:a003590Google Scholar
  200. Ycas M (1974) On earlier states of the biochemical system. J Theor Biol 44:145–160PubMedGoogle Scholar
  201. Ye J, Osborne AR, Groll M, Rapoport TA (2004) RecA-like motor ATPases—lessons from structures. Biochim Biophys Acta 1659:1–18PubMedGoogle Scholar
  202. Yomo T, Saito S, Sasai M (1999) Gradual development of protein-like global structures through functional selection. Nat Struct Biol 6:743–746PubMedGoogle Scholar
  203. Zempleni J, Wijeratne SS, Hassan YI (2009) Biotin. Biofactors 35:36–46PubMedGoogle Scholar
  204. Zhang Y, Hubner I, Arakaki A, Shakhnovich E, Skolnick J (2006) On the origin and highly likely completeness of single-domain protein structures. Proc Natl Acad Sci USA 103:2605–2610PubMedGoogle Scholar
  205. Zhang W, Dunkle JA, Cate JHD (2009) Structures of the ribosome in intermediate states of ratcheting. Science 325:1014–1017PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Gustavo Caetano-Anollés
    • 1
    Email author
  • Kyung Mo Kim
    • 2
  • Derek Caetano-Anollés
    • 1
  1. 1.Evolutionary Bioinformatics Laboratory, Department of Crop SciencesUniversity of IllinoisUrbanaUSA
  2. 2.Korean Bioinformation Center (KOBIC), Korea Research Institute of Bioscience and Biotechnology (KRIBB)DaejeonKorea

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