Appendix 1. Minimum Clusters of Orthologous Groups (COG) in the LUCA Genome Group No. COG (J) Translation, 8 Glutamyl-tRNA synthetase ribosomal 9 Putative translation factor (SUA5) structure and 12 Predicted GTPase, probable translation factor biogenesis 13 Alanyl-tRNA synthetase 16 Phenylalanyl-tRNA synthetase alpha subunit 17 Aspartyl-tRNA synthetase 18 Arginyl-tRNA synthetase 23 Translation initiation factor 1 (eIF-1/SUI1) and related proteins 24 Methionine aminopeptidase 30 Dimethyladenosine transferase (rRNA methylation) 48 Ribosomal protein S12 49 Ribosomal protein S7 51 Ribosomal protein S10 52 Ribosomal protein S2 60 Isoleucyl-tRNA synthetase 72 Phenylalanyl-tRNA synthetase beta subunit 80 Ribosomal protein L11 81 Ribosomal protein L1 87 Ribosomal protein L3 88 Ribosomal protein L4 89 Ribosomal protein L23 90 Ribosomal protein L2 91 Ribosomal protein L22 92 Ribosomal protein S3 93 Ribosomal protein L14 94 Ribosomal protein L5 96 Ribosomal protein S8 97 Ribosomal protein L6P/L9E 98 Ribosomal protein S5 99 Ribosomal protein S13 100 Ribosomal protein S11 101 Pseudouridylate synthase 102 Ribosomal protein L13 103 Ribosomal protein S9 124 Histidyl-tRNA synthetase 130 Pseudouridine synthase 143 Methionyl-tRNA synthetase 162 Tyrosyl-tRNA synthetase 172 Seryl-tRNA synthetase 180 Tryptophanyl-tRNA synthetase 182 Predicted translation initiation factor 2B subunit, eIF-2B alpha/beta/delta family 184 Ribosomal protein S15P/S13E 185 Ribosomal protein S19 186 Ribosomal protein S17 197 Ribosomal protein L16/L10E 198 Ribosomal protein L24 199 Ribosomal protein S14 200 Ribosomal protein L15 231 Translation elongation factor P (EF-P)/translation initiation factor 5A (eIF-5A) 244 Ribosomal protein L10 252 L-asparaginase/archaeal Glu-tRNAGln amidotransferase subunit D 255 Ribosomal protein L29 256 Ribosomal protein L18 343 Queuine/archaeosine tRNA-ribosyltransferase 361 Translation initiation factor 1 (IF-1) 423 Glycyl-tRNA synthetase (class II) 441 Threonyl-tRNA synthetase 442 Prolyl-tRNA synthetase 480 Translation elongation factors (GTPases) 495 Leucyl-tRNA synthetase 522 Ribosomal protein S4 and related proteins 525 Valyl-tRNA synthetase 532 Translation initiation factor 2 (IF-2; GTPase) 621 2-methylthioadenine synthetase 1093 Translation initiation factor 2, alpha subunit (eIF-2alpha) 1258 Predicted pseudouridylate synthase 1325 Predicted exosome subunit 1358 Ribosomal protein HS6-type (S12/L30/L7a) 1369 RNase P/RNase MRP subunit POP5 1383 Ribosomal protein S17E 1384 Lysyl-tRNA synthetase (class I) 1471 Ribosomal protein S4E 1491 Predicted RNA-binding protein 1498 Protein implicated in ribosomal biogenesis Nop56p homolog 1499 NMD protein affecting ribosome stability and mRNA decay 1500 Predicted exosome subunit 1503 Peptide chain release factor 1 (eRF1) 1514 2'-5' RNA ligase 1534 Predicted RNA-binding protein containing KH domain possibly ribosomal protein 1549 Queuine tRNA-ribosyltransferases, contain PUA domain 1552 Ribosomal protein L40E 1588 RNase P/RNase MRP subunit p29 1601 Translation initiation factor 2, beta subunit (eIF-2beta)/eIF-5 N-terminal domain 1603 RNase P/RNase MRP subunit p30 1631 Ribosomal protein L44E 1632 Ribosomal protein L15E 1676 tRNA splicing endonuclease 1717 Ribosomal protein L32E 1727 Ribosomal protein L18E 1736 Diphthamide synthase subunit DPH2 1746 tRNA nucleotidyltransferase (CCA-adding enzyme) 1798 Diphthamide biosynthesis methyltransferase 1841 Ribosomal protein L30/L7E 1867 N2,N2-dimethylguanosine tRNA methyltransferase 1889 Fibrillarin-like rRNA methylase 1890 Ribosomal protein S3AE 1911 Ribosomal protein L30E 1976 Translation initiation factor 6 (eIF-6) 1997 Ribosomal protein L37AE/L43A 1998 Ribosomal protein S27AE 2004 Ribosomal protein S24E 2007 Ribosomal protein S8E 2016 Predicted RNA-binding protein (contains PUA domain) 2023 RNase P subunit RPR2 2051 Ribosomal protein S27E 2053 Ribosomal protein S28E/S33 2058 Ribosomal protein L12E/L44/L45/RPP1/RPP2 2075 Ribosomal protein L24E 2092 Translation elongation factor EF-1beta 2097 Ribosomal protein L31E 2125 Ribosomal protein S6E (S10) 2126 Ribosomal protein L37E 2139 Ribosomal protein L21E 2147 Ribosomal protein L19E 2157 Ribosomal protein L20A (L18A) 2163 Ribosomal protein L14E/L6E/L27E 2167 Ribosomal protein L39E 2174 Ribosomal protein L34E 2238 Ribosomal protein S19E (S16A) 2260 Predicted Zn-ribbon RNA-binding protein 2263 Predicted RNA methylase 2511 Archaeal Glu-tRNAGln amidotransferase subunit E (contains GAD domain) 2519 tRNA(1-methyladenosine) methyltransferase and related methyltransferases 2888 Predicted Zn-ribbon RNA-binding protein with a function in translation 2890 Methylase of polypeptide chain release factors 3277 RNA-binding protein involved in rRNA processing 5256 Translation elongation factor EF-1alpha (GTPase) 5257 Translation initiation factor 2, gamma subunit (eIF-2gamma; GTPase) (A) RNA 430 RNA 3'-terminal phosphate cyclase processing and 2136 Predicted exosome subunit/U3 small nucleolar ribonucleoprotein (snoRNP) component, modification contains IMP4 domain (K) 85 DNA-directed RNA polymerase, beta subunit/140 kD subunit Transcription 86 DNA-directed RNA polymerase, beta' subunit/160 kD subunit 195 Transcription elongation factor 202 DNA-directed RNA polymerase, alpha subunit/40 kD subunit 250 Transcription antiterminator 640 Predicted transcriptional regulators 864 Predicted transcriptional regulators containing the CopG/Arc/MetJ DNA-binding domain and a metal-binding domain 1095 DNA-directed RNA polymerase, subunit E' 1243 Histone acetyltransferase 1293 Predicted RNA-binding protein homologous to eukaryotic snRNP 1308 Transcription factor homologous to NACalpha-BTF3 1321 Mn-dependent transcriptional regulator 1378 Predicted transcriptional regulators 1395 Predicted transcriptional regulator 1405 Transcription initiation factor TFIIIB, Brf1 subunit 1522 Transcriptional regulators 1581 Archaeal DNA-binding protein 1644 DNA-directed RNA polymerase, subunit N (RpoN/RPB10) 1675 Transcription initiation factor IIE, alpha subunit 1758 DNA-directed RNA polymerase, subunit K/omega 1761 DNA-directed RNA polymerase, subunit L 1813 Predicted transcription factor, homolog of eukaryotic MBF1 1846 Transcriptional regulators 1996 DNA-directed RNA polymerase, subunit RPC10 (contains C4-type Zn-finger) 2012 DNA-directed RNA polymerase, subunit H, RpoH/RPB5 2093 DNA-directed RNA polymerase, subunit E'' 2101 TATA-box binding protein (TBP), component of TFIID and TFIIIB (L) Replication, 84 Mg-dependent DNase recombination 164 Ribonuclease HII and repair 177 Predicted EndoIII-related endonuclease 258 5'-3' exonuclease (including N-terminal domain of PolI) 270 Site-specific DNA methylase 350 Methylated DNA-protein cysteine methyltransferase 358 DNA primase (bacterial type) 417 DNA polymerase elongation subunit (family B) 419 ATPase involved in DNA repair 420 DNA repair exonuclease 468 RecA/RadA recombinase 470 ATPase involved in DNA replication 550 Topoisomerase IA 592 DNA polymerase sliding clamp subunit (PCNA homolog) 608 Single-stranded DNA-specific exonuclease 1041 Predicted DNA modification methylase 1107 Archaea-specific RecJ-like exonuclease, contains DnaJ-type Zn finger domain 1111 ERCC4-like helicases 1112 Superfamily I DNA and RNA helicases and helicase subunits 1241 Predicted ATPase involved in replication control, Cdc46/Mcm family 1311 Archaeal DNA polymerase II, small subunit/DNA polymerase delta, subunit B 1389 DNA topoisomerase VI, subunit B 1423 ATP-dependent DNA ligase, homolog of eukaryotic ligase III 1467 Eukaryotic-type DNA primase, catalytic (small) subunit 1525 Micrococcal nuclease (thermonuclease) homologs 1591 Holliday junction resolvase - archaeal type 1599 Single-stranded DNA-binding replication protein A (RPA), large (70 kD) subunit and related ssDNA-binding proteins 1637 Predicted nuclease of the RecB family 1697 DNA topoisomerase VI, subunit A 1793 ATP-dependent DNA ligase 1933 Archaeal DNA polymerase II, large subunit 1948 ERCC4-type nuclease 2219 Eukaryotic-type DNA primase, large subunit (B) Chromatin 123 Deacetylases, including yeast histone deacetylase and acetoin utilization protein structure and 2036 Histones H3 and H4 dynamics (D) Cell cycle 37 Predicted ATPase of the PP-loop superfamily implicated in cell cycle control control, cell 206 Cell division GTPase division, 455 ATPases involved in chromosome partitioning chromosome 489 ATPases involved in chromosome partitioning partitioning 1192 ATPases involved in chromosome partitioning 1718 Serine/threonine protein kinase involved in cell cycle control (T) Signal 467 RecA-superfamily ATPases implicated in signal transduction transduction 589 Universal stress protein UspA and related nucleotide-binding proteins mechanisms 3642 Mn2+-dependent serine/threonine protein kinase (M) Cell wall/ 438 Glycosyltransferase membrane/ 449 Glucosamine 6-phosphate synthetase, contains amidotransferase and phosphosugar envelope isomerase domains, biogenesis 451 Nucleoside-diphosphate-sugar epimerases 463 Glycosyltransferases involved in cell wall biogenesis 472 UDP-N-acetylmuramyl pentapeptide phosphotransferase/UDP-N-acetylglucosamine-1- phosphate transferase 668 Small-conductance mechanosensitive channel 750 Predicted membrane-associated Zn-dependent proteases 1 794 Predicted sugar phosphate isomerase involved in capsule formation 1208 Nucleoside-diphosphate-sugar pyrophosphorylase involved in lipopolysaccharide biosynthesis/translation initiation factor 2B, gamma/epsilon subunits (eIF-2Bgamma/eIF- 2Bepsilon) (U) ntracellular 201 Preprotein translocase subunit SecY trafficking, 341 Preprotein translocase subunit SecF secretion, and 342 Preprotein translocase subunit SecD vesicular 541 Signal recognition particle GTPase transport 552 Signal recognition particle GTPase 681 Signal peptidase I 1400 Signal recognition particle 19 kDa protein 1989 Type II secretory pathway, prepilin signal peptidase PulO and related peptidases 2064 Flp pilus assembly protein TadC 2443 Preprotein translocase subunit Sss1 4962 Flp pilus assembly protein, ATPase CpaF (O) Posttransl- 68 Hydrogenase maturation factor ational 71 Molecular chaperone (small heat shock protein) modification, 298 Hydrogenase maturation factor protein 309 Hydrogenase maturation factor turnover, 330 Membrane protease subunits, stomatin/prohibitin homologs chaperones 396 ABC-type transport system involved in Fe-S cluster assembly, ATPase component 409 Hydrogenase maturation factor 459 Chaperonin GroEL (HSP60 family) 464 ATPases of the AAA+ class 492 Thioredoxin reductase 501 Zn-dependent protease with chaperone function 533 Metal-dependent proteases with possible chaperone activity 555 ABC-type sulfate transport system, permease component 602 Organic radical activating enzymes 638 20S proteasome, alpha and beta subunits 1047 FKBP-type peptidyl-prolyl cis-trans isomerases 2 1067 Predicted ATP-dependent protease 1180 Pyruvate-formate lyase-activating enzyme 1222 ATP-dependent 26S proteasome regulatory subunit 1370 Prefoldin, molecular chaperone implicated in de novo protein folding, alpha subunit 1382 Prefoldin, chaperonin cofactor 1730 Predicted prefoldin, molecular chaperone implicated in de novo protein folding 1899 Deoxyhypusine synthase 2518 Protein-L-isoaspartate carboxylmethyltransferase (C) Energy 39 Malate/lactate dehydrogenases production and 45 Succinyl-CoA synthetase, beta subunit conversion 74 Succinyl-CoA synthetase, alpha subunit 243 Anaerobic dehydrogenases, typically selenocysteine-containing 247 Fe-S oxidoreductase 371 Glycerol dehydrogenase and related enzymes 473 Isocitrate/isopropylmalate dehydrogenase 479 Succinate dehydrogenase/fumarate reductase, Fe-S protein subunit 543 2-polyprenylphenol hydroxylase and related flavodoxin oxidoreductases 636 F0F1-type ATP synthase, subunit c/Archaeal/vacuolar-type H+-ATPase, subunit K 644 Dehydrogenases (flavoproteins) 650 Formate hydrogenlyase subunit 4 674 Pyruvate:ferredoxin oxidoreductase and related 2-oxoacid:ferredoxin oxidoreductases, alpha subunit 680 Ni,Fe-hydrogenase maturation factor 716 Flavodoxins 731 Fe-S oxidoreductases 778 Nitroreductase 1012 NAD-dependent aldehyde dehydrogenases 1013 Pyruvate:ferredoxin oxidoreductase and related 2-oxoacid:ferredoxin oxidoreductases, beta subunit 1014 Pyruvate:ferredoxin oxidoreductase and related 2-oxoacid:ferredoxin oxidoreductases, gamma subunit 1029 Formylmethanofuran dehydrogenase subunit B 1032 Fe-S oxidoreductase 1035 Coenzyme F420-reducing hydrogenase, beta subunit 1036 Archaeal flavoproteins 1053 Succinate dehydrogenase/fumarate reductase, flavoprotein subunit 1142 Fe-S-cluster-containing hydrogenase components 2 1144 Pyruvate:ferredoxin oxidoreductase and related 2-oxoacid:ferredoxin oxidoreductases, delta subunit 1145 Ferredoxin 1146 Ferredoxin 1148 Heterodisulfide reductase, subunit A and related polyferredoxins 1149 MinD superfamily P-loop ATPase containing an inserted ferredoxin domain 1150 Heterodisulfide reductase, subunit C 1151 6Fe-6S prismane cluster-containing protein 1152 CO dehydrogenase/acetyl-CoA synthase alpha subunit 1153 Formylmethanofuran dehydrogenase subunit D 1155 Archaeal/vacuolar-type H+-ATPase subunit A 1156 Archaeal/vacuolar-type H+-ATPase subunit B 1229 Formylmethanofuran dehydrogenase subunit A 1249 Pyruvate/2-oxoglutarate dehydrogenase complex, dihydrolipoamide dehydrogenase (E3) component, and related enzymes 1269 Archaeal/vacuolar-type H+-ATPase subunit I 1304 L-lactate dehydrogenase (FMN-dependent) and related alpha-hydroxy acid dehydrogenases 1390 Archaeal/vacuolar-type H+-ATPase subunit E 1394 Archaeal/vacuolar-type H+-ATPase subunit D 1436 Archaeal/vacuolar-type H+-ATPase subunit F 1456 CO dehydrogenase/acetyl-CoA synthase gamma subunit (corrinoid Fe-S protein) 1527 Archaeal/vacuolar-type H+-ATPase subunit C 1592 Rubrerythrin 1614 CO dehydrogenase/acetyl-CoA synthase beta subunit 1625 Fe-S oxidoreductase, related to NifB/MoaA family 1819 Glycosyl transferases, related to UDP-glucuronosyltransferase 1880 CO dehydrogenase/acetyl-CoA synthase epsilon subunit 1838 Tartrate dehydratase beta subunit/Fumarate hydratase class I, C-terminal domain 1908 Coenzyme F420-reducing hydrogenase, delta subunit 1927 Coenzyme F420-dependent N(5), N(10)-methenyltetrahydromethanopterin dehydrogenase 1941 Coenzyme F420-reducing hydrogenase, gamma subunit 1951 Tartrate dehydratase alpha subunit/Fumarate hydratase class I, N-terminal domain 2037 Formylmethanofuran:tetrahydromethanopterin formyltransferase 2048 Heterodisulfide reductase, subunit B 2055 Malate/L-lactate dehydrogenases 2069 CO dehydrogenase/acetyl-CoA synthase delta subunit (corrinoid Fe-S protein) 2141 Coenzyme F420-dependent N5,N10-methylene tetrahydromethanopterin reductase and related flavin-dependent oxidoreductases 2218 Formylmethanofuran dehydrogenase subunit C 2221 Dissimilatory sulfite reductase (desulfoviridin), alpha and beta subunits 2710 Nitrogenase molybdenum-iron protein, alpha and beta chains 3259 Coenzyme F420-reducing hydrogenase, alpha subunit 3260 Ni,Fe-hydrogenase III small subunit 3261 Ni,Fe-hydrogenase III large subunit 4074 H2-forming N5,N10-methylenetetrahydromethanopterin dehydrogenase (G) 57 Glyceraldehyde-3-phosphate dehydrogenase/erythrose-4-phosphate dehydrogenase Carbohydrate 61 Predicted sugar kinase transport and 63 H2-forming N5,N10-methylenetetrahydromethanopterin dehydrogenase metabolism 120 Ribose 5-phosphate isomerase 126 3-phosphoglycerate kinase 148 Enolase 149 Triosephosphate isomerase 235 Ribulose-5-phosphate 4-epimerase and related epimerases and aldolases 269 3-hexulose-6-phosphate synthase and related proteins 483 Archaeal fructose-1,6-bisphosphatase and related enzymes of inositol monophosphatase family 524 Sugar kinases, ribokinase family 574 Phosphoenolpyruvate synthase/pyruvate phosphate dikinase 662 Mannose-6-phosphate isomerase 1082 Sugar phosphate isomerases/epimerases 1109 Phosphomannomutase 1363 Cellulase M and related proteins 1830 DhnA-type fructose-1,6-bisphosphate aldolase and related enzymes 1980 Archaeal fructose 1,6-bisphosphatase 2074 2-phosphoglycerate kinase 3635 Predicted phosphoglycerate mutase, AP superfamily 3839 ABC-type sugar transport systems, ATPase components (E) Amino acid 2 Acetylglutamate semialdehyde dehydrogenase transport and 6 Xaa-Pro aminopeptidase metabolism 10 Arginase/agmatinase/formimionoglutamate hydrolase, arginase family 65 3-isopropylmalate dehydratase large subunit 66 3-isopropylmalate dehydratase small subunit 75 Serine-pyruvate aminotransferase/archaeal aspartate aminotransferase 76 Glutamate decarboxylase and related PLP-dependent proteins 78 Ornithine carbamoyltransferase 79 Histidinol-phosphate/aromatic aminotransferase and cobyric acid decarboxylase 111 Phosphoglycerate dehydrogenase and related dehydrogenases 112 Glycine/serine hydroxymethyltransferase 119 Isopropylmalate/homocitrate/citramalate synthases 136 Aspartate-semialdehyde dehydrogenase 174 Glutamine synthetase 289 Dihydrodipicolinate reductase 329 Dihydrodipicolinate synthase/N-acetylneuraminate lyase 367 Asparagine synthase (glutamine-hydrolyzing) 436 Aspartate/tyrosine/aromatic aminotransferase 440 Acetolactate synthase, small (regulatory) subunit 460 Homoserine dehydrogenase 498 Threonine synthase 527 Aspartokinases 548 Acetylglutamate kinase 560 Phosphoserine phosphatase 620 Methionine synthase II (cobalamin-independent) 1387 Histidinol phosphatase and related hydrolases of the PHP family 1812 Archaeal S-adenosylmethionine synthetase 4992 Ornithine/acetylornithine aminotransferase (F) Nucleotide 5 Purine nucleoside phosphorylase transport and 15 Adenylosuccinate lyase metabolism 34 Glutamine phosphoribosylpyrophosphate amidotransferase 41 Phosphoribosylcarboxyaminoimidazole (NCAIR) mutase 44 Dihydroorotase and related cyclic amidohydrolases 46 Phosphoribosylformylglycinamidine (FGAM) synthase, synthetase domain 47 Phosphoribosylformylglycinamidine synthase, glutamine amidotransferase domain 104 Adenylosuccinate synthase 105 Nucleoside diphosphate kinase 125 Thymidylate kinase 127 Xanthosine triphosphate pyrophosphatase 150 Phosphoribosylaminoimidazole (AIR) synthetase 151 Phosphoribosylamine-glycine ligase 152 Phosphoribosylaminoimidazolesuccinocarboxamide (SAICAR) synthase 167 Dihydroorotate dehydrogenase 284 Orotidine-5'-phosphate decarboxylase 402 Cytosine deaminase and related metal-dependent hydrolases 461 Orotate phosphoribosyltransferase 462 Phosphoribosylpyrophosphate synthetase 503 Adenine/guanine phosphoribosyltransferases and related PRPP-binding proteins 504 CTP synthase (UTP-ammonia lyase) 516 IMP dehydrogenase/GMP reductase 518 GMP synthase - Glutamine amidotransferase domain 519 GMP synthase, PP-ATPase domain/subunit 528 Uridylate kinase 540 Aspartate carbamoyltransferase, catalytic chain 717 Deoxycytidine deaminase 1051 ADP-ribose pyrophosphatase 1102 Cytidylate kinase 1328 Oxygen-sensitive ribonucleoside-triphosphate reductase 1437 Adenylate cyclase, class 2 (thermophilic) 1618 Predicted nucleotide kinase 1781 Aspartate carbamoyltransferase, regulatory subunit 1828 Phosphoribosylformylglycinamidine (FGAM) synthase, PurS component 1936 Predicted nucleotide kinase (related to CMP and AMP kinases) 2019 Archaeal adenylate kinase (H) Coenzyme 43 3-polyprenyl-4-hydroxybenzoate decarboxylase and related decarboxylases transport and 142 Geranylgeranyl pyrophosphate synthase metabolism 157 Nicotinate-nucleotide pyrophosphorylase 163 3-polyprenyl-4-hydroxybenzoate decarboxylase 171 NAD synthase 214 Pyridoxine biosynthesis enzyme 237 Dephospho-CoA kinase 294 Dihydropteroate synthase and related enzymes 301 Thiamine biosynthesis ATP pyrophosphatase 303 Molybdopterin biosynthesis enzyme 311 Predicted glutamine amidotransferase involved in pyridoxine biosynthesis 315 Molybdenum cofactor biosynthesis enzyme 351 Hydroxymethylpyrimidine/phosphomethylpyrimidine kinase 368 Cobalamin-5-phosphate synthase 379 Quinolinate synthase 382 4-hydroxybenzoate polyprenyltransferase and related prenyltransferases 452 Phosphopantothenoylcysteine synthetase/decarboxylase 499 S-adenosylhomocysteine hydrolase 521 Molybdopterin biosynthesis enzymes 611 Thiamine monophosphate kinase 720 6-pyruvoyl-tetrahydropterin synthase 746 Molybdopterin-guanine dinucleotide biosynthesis protein A 1270 Cobalamin biosynthesis protein CobD/CbiB 1339 Transcriptional regulator of a riboflavin/FAD biosynthetic operon 1635 Flavoprotein involved in thiazole biosynthesis 1763 Molybdopterin-guanine dinucleotide biosynthesis protein 1767 Triphosphoribosyl-dephospho-CoA synthetase 2038 NaMN:DMB phosphoribosyltransferase 2266 GTP:adenosylcobinamide-phosphate guanylyltransferase 2896 Molybdenum cofactor biosynthesis enzyme (I) Lipid 20 Undecaprenyl pyrophosphate synthase transport and 170 Dolichol kinase metabolism 183 Acetyl-CoA acetyltransferase 575 CDP-diglyceride synthetase 615 Cytidylyltransferase 671 Membrane-associated phospholipid phosphatase 1257 Hydroxymethylglutaryl-CoA reductase 1267 Phosphatidylglycerophosphatase A and related proteins 1577 Mevalonate kinase 3425 3-hydroxy-3-methylglutaryl CoA synthase (P) Inorganic 168 Trk-type K+ transport systems, membrane components ion transport 306 Phosphate/sulphate permeases and metabolism 370 Fe2+ transport system protein B 477 Permeases of the major facilitator superfamily 530 Ca2+/Na+ antiporter 569 K+ transport systems, NAD-binding component 619 ABC-type cobalt transport system, permease component CbiQ and related transporters 704 Phosphate uptake regulator 725 ABC-type molybdate transport system, periplasmic component 1122 ABC-type cobalt transport system, ATPase component 1226 3-hydroxy-3-methylglutaryl CoA synthase 1918 Fe2+ transport system protein A (Q) Secondary 179 2-keto-4-pentenoate hydratase/2-oxohepta-3-ene-1,7-dioic acid hydratase(catechol pathway) metabolite 500 SAM-dependent methyltransferases biosynthesis, transport and catabolism (R) General 73 EMAP domain function 312 Predicted Zn-dependent proteases and their inactivated homologs prediction only 375 Zn finger protein HypA/HybF (possibly regulating hydrogenase expression) 433 Predicted ATPase 446 Uncharacterized NAD(FAD)-dependent dehydrogenases 456 Acetyltransferases 491 Zn-dependent hydrolases, including glyoxylases 517 FOG: CBS domain 535 Predicted Fe-S oxidoreductases 603 Predicted PP-loop superfamily ATPase 622 Predicted phosphoesterase 663 Carbonic anhydrases/acetyltransferases, isoleucine patch superfamily 714 MoxR-like ATPases 1011 Predicted hydrolase (HAD superfamily) 1019 Predicted nucleotidyltransferase 1078 HD superfamily phosphohydrolases 1084 Predicted GTPase 1094 Predicted RNA-binding protein (contains KH domains) 1100 GTPase SAR1 and related small G proteins 1163 Predicted GTPase 1201 Lhr-like helicases 1204 Superfamily II helicase 1205 Distinct helicase family with a unique C-terminal domain including a metal-binding cysteine cluster 1234 ATPase components of various ABC-type transport systems, contain duplicated ATPase 1235 Metal-dependent hydrolases of the beta-lactamase superfamily I 1237 Metal-dependent hydrolases of the beta-lactamase superfamily II 1245 Predicted ATPase, RNase L inhibitor (RLI) homolog 1313 Uncharacterized Fe-S protein PflX, homolog of pyruvate formate lyase activating proteins 1326 Uncharacterized archaeal Zn-finger protein 1355 Predicted dioxygenase 1365 Predicted ATPase (PP-loop superfamily) 1407 Predicted ICC-like phosphoesterases 1412 Uncharacterized proteins of PilT N-term./Vapc superfamily 1418 Predicted HD superfamily hydrolase 1439 Predicted nucleic acid-binding protein, consists of a PIN domain and a Zn-ribbon module 1458 Predicted DNA-binding protein containing PIN domain 1537 Predicted RNA-binding proteins 1545 Predicted nucleic-acid-binding protein containing a Zn-ribbon 1571 Predicted DNA-binding protein containing a Zn-ribbon domain 1608 Predicted archaeal kinase 1646 Predicted phosphate-binding enzymes, TIM-barrel fold 1759 ATP-utilizing enzymes of ATP-grasp superfamily (probably carboligases) 1779 C4-type Zn-finger protein 1782 Predicted metal-dependent RNase, consists of a metallo-beta-lactamase domain and an RNA-binding KH domain 1818 Predicted RNA-binding protein, contains THUMP domain 1829 Predicted metal-dependent RNase, consists of a metallo-beta-lactamase domain and an RNA-binding KH domain 1831 Predicted metal-dependent hydrolase (urease superfamily) 1855 ATPase (PilT family) 1907 Predicted archaeal sugar kinases 1938 Archaeal enzymes of ATP-grasp superfamily 1964 Predicted Fe-S oxidoreductases 1988 Predicted membrane-bound metal-dependent hydrolases 2047 Uncharacterized protein (ATP-grasp superfamily) 2102 Predicted ATPases of PP-loop superfamily 2118 DNA-binding protein 2129 Predicted phosphoesterases, related to the Icc protein 2151 Predicted metal-sulfur cluster biosynthetic enzyme 2220 Predicted Zn-dependent hydrolases of the beta-lactamase fold 2244 Membrane protein involved in the export of O-antigen and teichoic acid 2520 Predicted methyltransferase 3269 Predicted RNA-binding protein, contains TRAM domain (S) Unknown 11, 62, 32, 327, 392, 432, 585, 1303, 1371, 1379, 1373, 1422, 1430, 1432, 1433, 1460, 1469, 1578, proteins 1617, 1627, 1628, 1679, 1690, 1698, 1701, 1720, 1784, 1786, 1814, 1833, 1844, 1849, 1888, 1909, 1916, 1931, 1945, 1990, 1991, 1992, 2029, 2034, 2078, 2083, 2450, 2454, 2457, 2892 COG Nos. that are present in all of the ancient eight are shown in bold font; COG Nos. that are present in all of the ancient six but not in one or both of Ape and Pae are shown in non-bold font; COG Nos. that are not included in any of the minimal gene sets I-VI are shown in italics; the underlined COGs are common to the methanogenesis pathways of Mka, Mth and Mja.