Table 2.
Evolutionary history of trans-kingdom gene fusions
| COG A | Protein function | COG B | Protein function | Kingdom pattern* | Principal mode of evolution† | Fusion | Gene juxtaposition‡ | Evolutionary scenario |
| COG0046 | Phospho-ribosyl-formylglycinamidine (FGAM) synthase, synthetase domain | COG0047 | Phospho-ribosyl-formyl-glycinamidine (FGAM) synthase glutamine Amidotransferase domain | -be | HGT | Ecol, Paer, Vcho, Hinf, Xfas, Nmen | Pyro, Paby, Tmar, Drad, Bsub, Bhal | One fusion event, fused gene transfer between eukaryotes and proteobacteria |
| COG0067 | Glutamate synthase domain 1 | COG0069 | Glutamate synthase domain 2 | -be | HGT | Most bacteria | Aful, Mjan, Tmar | One fusion event, fused gene transfer between eukaryotes and bacteria |
| COG0067 | Glutamate synthase domain 1 | COG0070 | Glutamate synthase domain 3 | -be | HGT | Most bacteria | - | One fusion event, fused gene transfer between eukaryotes and bacteria |
| COG0069 | Glutamate synthase domain 2 | COG0070 | Glutamate synthase domain 3 | -be | HGT | Most bacteria | Aful, Mjan, Mthe | One fusion event, fused gene transfer between eukaryotes and bacteria |
| COG0139 | Phospho-ribosyl-AMP cyclohydrolase (histidine biosynthesis) | COG0140 | Phospho-ribosyl-ATP pyrophospho-hydrolase (histidine biosynthesis) | -be | Most bacteria | - | Uncertain | |
| COG0145 | N-methylhydaintoinase A | COG0146 | N-methylhydaintoinase B | -be | HGT | Mtub, Syne, Scer | Mjan, Aero, Hpyl | One fusion event, fused gene transfer between eukaryotes and (the ancestor of) Cyanobacteria and Actinomycetes |
| COG0147 | Anthranilate/para-aminobenzoate synthase component I | COG0512 | Anthranilate/para-aminobenzoate synthase component II | -be | IFE | Nmen, Cjej, Paer, Scer | Aful, Mthe, Taci, Aero, Tmar, Drad, Bsub, Bhal, Ecol, Vcho, Xfas | Independent fusion events in eukaryotes and bacteria |
| COG0169 | Shikimate 5-dehydrogenase | COG0710 | 3-dehydro-quinate dehydratase | -be | IFE | Ctra, Cpne, Scer | Paby¶Ecol | Independent fusion events in eukaryotes and bacteria |
| COG0294 | Dihydropteroate synthase | COG0801 | 7,8-dihydro-6-hydroxymethylpterin-pyrophosphokinase | -be | IFE | Ctra, Cpne, Scer | Llac¶, Tmar, Drad, Bsub, Bhal | Independent fusion events in eukaryotes and bacteria |
| COG0304 | 3-oxoacyl-(acyl-carrier-protein) synthase | COG0331 | (acyl-carrier-protein) S-malonyl-transferase | -be | HGT | Mtub, Scer | Drad, Ecol, Vcho | One fusion event, fused gene transfer between eukaryotes and bacteria |
| COG0331 | 3-oxoacyl-(acyl-carrier-protein) synthase | COG2030 | Acyl dehydratase | -be | HGT | Mtub, Bsub, Scer | - | Fused gene transfer between eukaryotes and Actinomycetes; additional, independent fusions in bacteria |
| COG0337 | 3-dehydroquinate synthetase | COG0703 | Shikimate kinase | -be | IFE | Tmar, Scer | Drad, Mtub, Proteo-bacteria, Ctra, Cpne | Independent fusion events in eukaryotes and bacteria (with different domain organizations) |
| COG0403 | Glycine cleavage system protein P (pyridoxal-binding), amino-terminal domain | COG1003 | Glycine cleavage system protein P (pyridoxal-binding), carboxy-terminal domain | -be | HGT | Drad, Mtub, Syne, Ecol, Paer, Xfas, Nmen | Hbsp, Pyro, Taci, Aero, Tmar, Bsub, Bhal | One fusion event, fused gene transfer between eukaryotes and proteobacteria |
| COG0439 | Biotin carboxylase | COG0511 | Biotin carboxyl carrier protein | -be | HGT | Hbsp, Mtub, Rpxx, Scer | Bhal, Ecol, Paer Vcho, Hinf, Xfas, Nmen, Hpyl, Ctra, Cpne | One fusion event, fused gene transfer between eukaryotes and bacteria; additional, independent fusions in bacteria |
| COG0439 | Biotin carboxylase | COG1038 | Pyruvate carboxylase, carboxy-terminal domain/subunit | -be | HGT | Bsub, Scer | Mjan | One fusion event, fused gene transfer between eukaryotes and bacteria; subsequent domain accretion in eukaryotes |
| COG0439 | Biotin carboxylase | COG0825 | Acetyl-CoA carboxylase α-subunit | -be | HGT | Mtub, Scer | Hbsp, Rpxx | One fusion event, fused gene transfer between eukaryotes and bacteria; subsequent domain accretion in eukaryotes |
| COG0476 | Dinucleotide-utilizing enzyme involved in molybdopterin and thiamine biosynthesis | COG0607 | Rhodanese-related sulfurtransferase | -be | IFE | Mtub, Syne, Paer, Scer | - | Independent fusion events in x sulfurtransferase |
| COG0511 | Biotin carboxyl carrier protein | COG0825 | Acetyl-CoA carboxylase α-subunit | -be | IFE | Drad, Paer, Scer | Pyro, Tmar, Hbsp¥ | Independent fusion events in eukaryotes and bacteria |
| COG0664 | cAMP-binding domain | COG1752 | Esterase | -be | HGT | Mtub, Ccre||, Scer | - | One fusion event, fused gene transfer between eukaryotes and actinomycetes; an additional, independent fusion event in bacteria |
| COG1984 | Allophanate hydrolase subunit 2 | COG2049 | Allophanate hydrolase subunit 1 | -be | IFE | Bsub, Scer | Most bacteria | Independent fusion events in eukaryotes and bacteria |
| COG1155 | Archaeal/vacuolar-type H+-ATPase subunit A | COG1372 | Intein | a-e | IFE | Taci, Pyro, Scer | - | Independent fusion events in eukaryotes and archaea |
| COG0025 | Na+/H+ and K+/H+ antiporters | COG0569 | K+ transport systems, NAD-binding component | ab- | Hbsp, Bhal, Syne | - | Uncertain | |
| COG0062 | Uncharacterized, conserved protein | COG0063 | Predicted sugar kinase | ab- | AF | All archaea; all bacteria that have COG0062 | NA | One ancestral fusion; fission in eukaryotes |
| COG0069 | Glutamate synthase domain 2 | COG1037 | Ferredoxin-like domain | ab- | HGT | Aful, Mjan, Mthe, Tmar; (all that have COG1037) | NA | One ancestral fusion; fused gene transfer from archaea to bacteria (Thermotoga) |
| COG0077 | Prephenate dehydratase | COG1605 | Chorismate mutase | ab- | HGT | Aful, Aqua, Tmar, Ecol, Vcho, Paer, Hinf, Xfas, Nmen, Cjej | - | Fused gene transfer between bacteria and archaea (Archaeoglobus and Thermotoga lineages); additional, independent fusions in bacteria |
| COG0108 | 3,4-dihydroxy-2-butanone 4-phosphate synthase | COG0807 | GTP cyclohydrolase II | ab- | Aful, Aqua, Tmar, Drad, Mtub, Bsub, Bhal, Syne, Paer, Vcho, Xfas, Nmen, Hpyl, Cjej, Ctra, Cpne | - | Uncertain | |
| COG0280 | Phosphotransacetylase | COG0281 | Malic enzyme | ab- | HGT | Hbsp, Ecol, Hinf, Xfas, Rpxx | - | One fusion event, fused gene transfer from bacteria to archaea (Halobacterium) |
| COG0287 | Prephenate dehydrogenase | COG1605 | Chorismate mutase | ab- | IFE | Aful, Ecol, Vcho, Hinf | Taci, Aero, Ccre | Independent fusion events in archaea and bacteria |
| COG0301 | ATP pyrophosphatase (thiamine biosynthesis) | COG0607 | Rhodanese-related sulfurtransferase | ab- | IFE | Taci, Ecol, Vcho, Paer, Hinf | - | Independent fusion events in archaea and bacteria |
| COG0340 | Biotin-(acetyl-CoA carboxylase) ligase | COG1654 | Biotin operon repressor | ab- | HGT | Aful, Paby, Drad, Bsub, Bhal, Ecol, Paer, Vcho, Xfas; (all that have COG1654) | NA | One fusion event, fused gene transfer from bacteria to archaea (Archaeoglobus) |
| COG0351 | Hydroxymethyl-pyrimidine/phospho-methylpyrimidine kinase | COG1992 | Uncharacterized conserved protein | ab- | HGT | Hbsp, Mjan, Pyro, Aero, Tmar | - | One fusion event, fused gene transfer from archaea to bacteria (Thermotoga) |
| COG0468 | RecA/RadA recombinase | COG1372 | Intein | ab- | IFE | Hbsp, Pyro, Mtub | NA | Independent fusion events in archaea and bacteria |
| COG0475 | Kef-type K+ transport systems, membrane component | COG1226 | Kef-type K+ transport systems, NAD-binding component | ab- | HGT | Mthe, Ecol, Paer, Hinf, Xfas, Nmen, Cjej, Rpxx | - | One fusion event, fused gene transfer from bacteria to archaea (Methanobacterium) |
| COG0550 | Topoisomerase IA | COG0551 | Zn-finger domain associated with topoisomerase type IA | ab- | AF | Most bacteria and archaea | - | One ancestral fusion with subsequent fission in Aper, Aqua |
| COG0558 | Phosphatidyl-glycerophosphate synthase | COG1213 | Predicted sugar nucleotidyltransferase | ab- | HGT | Aful, Pyro, Aqua | Aero | One fusion event, fused gene transfer from archaea to bacteria (AquIFEx) |
| COG0560 | Phosphoserine phosphatase | COG2716 | ACT-domain-containing protein | ab- | Aful, Mtub, Paer | - | Uncertain | |
| COG0649 | NADH:ubiquinone oxidoreductase subunit 7 | COG0852 | NADH:ubiquinone oxidoreductase 27 kD subunit | ab- | HGT | Hbsp, Aqua, Ecol, Paer | Most archaea and bacteria | One fusion event, fused gene transfer from bacteria to archaea (Halobacterium) |
| COG0662 | Mannose-6-phosphate isomerase | COG0836 | Mannose-1-phosphate guanylyltransferase | ab- | HGT | Aful, Pyro, Aqua, Ecol, Paer, Vcho, Xfas, Hpyl, Cjej | - | Fused gene transfer from bacteria to archaea; a second, independent fusion event in bacteria |
| COG0674 | Pyruvate:ferredoxin oxidoreductase and related 2-oxoacid:ferredoxin oxidoreductases, alpha subunit | COG1014 | Pyruvate:ferredoxin oxidoreductase and related 2-oxoacid:ferredoxin oxidoreductases, gamma subunit | ab- | HGT | Aful, Hbsp, Taci, Aero, Mtub, Bhal, Syne, Ecol, Vcho, Tpal | Mjan, Mthe, Aqua, Tmar, Hpyl, Cjej | Fused gene transfer from archaea to bacteria; a second, independent fusion event in bacteria |
| COG0777 | Acetyl-CoA carboxylase β subunit | COG0825 | Acetyl-CoA carboxylase α subunit | ab- | HGT | Aful, Hbsp, Pyro, Tmar, Drad, Mtub, Bsub, Bhal, Paer, Rpxx | - | Fused gene transfer from bacteria to archaea; a second, independent fusion event in bacteria |
| COG1013 | Pyruvate:ferredoxin oxidoreductase and related 2-oxoacid:ferredoxin oxidoreductases, beta subunit | COG1014 | Pyruvate:ferredoxin oxidoreductase and related 2-oxoacid:ferredoxin oxidoreductases, gamma subunit | ab- | IFE | Mthe, Syne, Ecol, Vcho, Tpal | Aful, Taci, Aero, Mtub, Bhal | Independent fusion events in archaea and bacteria |
| COG1112 | Superfamily I DNA and RNA helicases and helicase subunits | COG2251 | Predicted metal-binding domain | ab- | IFE | Pyro, Mtub | - | Independent fusion events in archaea and bacteria |
| COG1239 | Mg-chelatase subunit ChlI | COG1240 | Mg-chelatase subunit ChlD | ab- | HGT | Hbsp, Mthe, Taci, Mtub, Syne | Mjan, Paer | Fused gene transfer between bacteria and archaea, with subsequent fissions |
| COG1361 | S-layer domain | COG1470 | Predicted membrane protein | ab- | HGT | Aful, Pyro, Bhal | - | One fusion event, fused gene transfer from archaea to bacteria |
| COG1387 | Histidinol phosphatase and related hydrolases of the PHP family | COG1796 | DNA polymerase IV (family X) | ab- | HGT | Mthe, Taci, Drad, Bsub, Bhal; (all prokaryotes that have COG1796) | NA | One fusion event, fused gene transfer between archaea to bacteria |
| COG1683 | Uncharacterized conserved protein | COG3272 | Uncharacterized conserved protein | ab- | HGT | Mthe, Paer, Vcho | - | One fusion event, fused gene transfer between archaea and bacteria (Methanobacterium and Vibrio/Pseudomonas, respectively) |
| COG1788 | Acyl-CoA:acetate CoA transferase alpha subunit | COG2057 | Acyl-CoA:acetate CoA transferase beta subunit | ab- | HGT | Hbsp, Taci, Aero, Drad, Bhal, Ecol | Mtub, Bsub, Paer, Hinf, Hpyl | Fused gene transfer between bacteria and archaea; a second, independent fusion event in bacteria |
| COG3261 | Ni, Fe-hydrogenase III large subunit | COG3262 | Ni, Fe-hydrogenase III component G | ab- | HGT | Paby, Mtub, Ecol | Pyro | One fusion event, fused gene transfer from bacteria to archaea |
| COG0518 | GMP synthase - Glutamine amidotransferase domain | COG0519 | GMP synthase-PP-ATPase domain | abe | HGT | Aero, Scer, most bacteria | Mthe, Pyro, Paby | Fused gene transfer among bacteria, archaea, and eukaryotes |
| COG0674 | Pyruvate:ferredoxin oxidoreductase and related 2-oxoacid:ferredoxin oxidoreductases, alpha subunit | COG1013 | Pyruvate:ferredoxin oxidoreductase and related 2-oxoacid:ferredoxin oxidoreductases, beta subunit | abe | HGT | Aful, Mthe, Taci, Pyro, Paby, Scer, Syne, Ecol, Vcho, Cjej, Tpal | Hbsp, Mjan, Aero, Aqua, Tmar, Mtub, Hpyl | Fused gene transfer from archaea to bacteria (α-proteobacteria) |
*Abbreviations: a, archaea, b, bacteria, e, eukaryotes; a dash indicates that the given kingdom is not represented in at least one of the fusion-linked COGs. †AF, ancestral fusion, HGT, horizontal gene transfer, IFE, independent fusion events. ‡ In several cases, the indicated genes are separated by one to three genes or their order is switched compared to that of the fusion components. §Paby, Pyrococcus abyssi, an archaeal genome not included in the master set of genomes analyzed in this study. ¶Llac, Lactococcus lactis, a bacterial genome not included in the master set of genomes analyzed in this study. ||Ccre, Caulobacter crescentus, a bacterial genome not included in the master set of genomes analyzed in this study. ¥Hbsp, Halobacterium sp., an archaeal genome not included in the master set of genomes analyzed in this study.