Table 1.
Interkingdom domain fusions and their probable origins
| IKF gene | Best 'native' hit | Best 'alien' hit | Protein function | Stand-alone | Comment |
| (GI number and gene | (E-value, amino acid | (E-value, amino | paralog of the | ||
| name) and origin | residue range, | acid residue range, | alien domain | ||
| of domains | species)/domain | species)/domain | |||
| function | function | ||||
| Archaea | |||||
| Aeropyrum pernix | |||||
| 5106104_ | 2621953_Mth | 2633525_Bs | Hydroxymethyl- | None | Pyrococci encode proteins with |
| APE2400 | 5e-27; | 4e-54; | pyrimidine | the same domain organization | |
| Archaeal-bacterial | 282-445; | 16-272; | phosphate kinase | andclosest similarity to A. pernix; | |
| uncharacterized domain | hydroxymethyl- | involved in thiamine | M. jannaschii encodes a protein | ||
| conserved among | pyrimidine phosphate | biosynthesis | with the same domain | ||
| archaea (homolog | kinase | (additional function?) | organization but low similarity; | ||
| of the amino-terminal | Mt encodes a HMP-kinase with | ||||
| domain of sialic acid | moderate similarity | ||||
| synthase) | |||||
| Methanococcus jannaschii | |||||
| 1591138_ | 2128140_Mj; | 7270033_At; | Unknown; | None | The amino-terminal domain is |
| MJ0434 | 1e-19; | 0.003; | possible role | present in several stand-alone | |
| Archaeal- | 2-94; | 120-222; | in stress response | copies in M. jannaschii, but | |
| bacterial-eukaryotic | uncharacterized | AIG2-like | otherwise, is seen mostly in | ||
| domain | stress-related | bacteria; the possibility of | |||
| protein | acquisition of a bacterial gene | ||||
| by the Methanococcus lineage | |||||
| is conceivable | |||||
| Methanobacterium thermoautotrophicum | |||||
| 2621249_ | 5103547_Ap; | 1651798_Ssp; | Membrane-associated | None | In Ssp, the amino-terminal |
| MTH204 | 1e-34; | 0.002; | 5-formyl- | domain is fused to another | |
| Archaeal- | 137-326; | 8-139; | tetrahydrofolate | uncharacterized domain. An | |
| eukaryotic/ | 5-formyl- | uncharacterized | cyclo-ligase(?); | ortholog with conserved | |
| bacterial | tetrahydrofolate | membrane-associated | exact function | domain organization is seen | |
| cyclo-ligase | domain | unknown | in Mycobacterium, but many | ||
| other bacteria encode stand- | |||||
| alone versions of this domain, | |||||
| which could be the actual sources | |||||
| of horizontal gene transfer | |||||
| 2621673_ | 3256572_Ph; | 2984130_Aa; | GTPase, possible | 2621855 | |
| MTH594 | 3e-10; | 6e-19; | role in signal | ||
| Archaeal-bacterial | 5-137; | 233-390; | transduction | ||
| inactivated RecA | GTPase | ||||
| domain | |||||
| 2622642_ | 5105992_Ap; | 2569943_Axy; | Glucose-1-phosphate | None | |
| MTH1523 | 3e-36; | 2e-05; | thymidylyl transferase/ | ||
| Archaeal-bacterial | 5-226; | 226-334; | glucose-6-phosphate | ||
| glucose-1-phosphate | mannose-6- | isomerase | |||
| thymidylyl transferase | phosphate isomerase | ||||
| Bacteria | |||||
| Aquifex aeolicus | |||||
| 2983622_ | 2633696_Bs; | 2650176_Af; | Signal | None | |
| aq_1151 | 5e-65; | 0.005; | transduction | ||
| Bacterial-archaeal | 325-795; | 116-279; | c-di-GMP | ||
| c-di-GMP phospho- | PAS/PAC | phospho-diesterase | |||
| diesterase | domain | ||||
| 2984285_ | 586875_Bs; | 3915955_Mj; | Molybdenum | None | |
| aq_2060 | 4e-63 | 3e-09; | cofactor | ||
| Bacterial-archaeal | 1-252; | 270-441; | bisynthesis enzyme(?) | ||
| PHP superfamily | pyruvate | ||||
| hydrolase | formate-lyase | ||||
| activating enzyme | |||||
| (Fe-S cluster | |||||
| oxidoreductase) | |||||
| Bacillus subtilis | |||||
| 2632283_yaaH, | 4980914_Tm | 399377_Rn | Chitinase | 2635915 | B. subtilis encodes two |
| 1945087_ydhD | 1e-06 | 2e-11 | paralogous proteins with the | ||
| Bacterial-eukaryotic | 2-92; | 221-402; | same domain architecture | ||
| LysM repeat domain | chitinase | ||||
| 2633242_yhcR | 645819_Dr; | 2622704_Mth; | Nuclease-nucleotidase | None | |
| Bacterial-archaeal | 1e-64; | 0.008 | (probable repair | ||
| 584-1068; | 151-257; | enzyme) | |||
| 5'-nucleotidase; | nucleic acid-binding | ||||
| 1175987_ | domain (OB-fold) | ||||
| ECR100; | |||||
| 2e-09; | |||||
| 377-521; | |||||
| thermonuclease | |||||
| 2632325_yabN | 4981449_Tm; | 3873806_Ce; | Methyl-transferase/ | None | Other than in chlamydiae, |
| Bacterial-eukaryotic | 2e-62; | 0.003; | pyro-phosphatase | the SWI domain is seen | |
| 223-483; | 7-125; | (metabolic enzyme | in eukaryotic chromatin- | ||
| MazG (predicted pyro- | SAM-dependent | of an unknown | associated proteins, leading | ||
| phosphatase) | methyl-transferase | pathway?) | to the suggestion that | ||
| chlamydial topoisomerase | |||||
| is involved in chromosome | |||||
| condensation | |||||
| Chlamydophyla pneumoniae | |||||
| 4377077_ | 730965_Bs; | 3581917_Sp; | DNA topoisomerase I, | 7189103 | SWI is a typical eukaryotic |
| CPn0769 | e-148; | 3e-10; | possibly involved in | domain not found in | |
| Bacterial-eukaryotic | 1-727; | 792-866; | chromatin | prokaryotes other than | |
| DNA topoisomerase I | SWI domain | condensation | chlamydia (the ortholog | ||
| in Chlamydia trachomatis has the | |||||
| same domain architecture) | |||||
| Deinococcus radiodurans | |||||
| 6459294_ | 7248325_Sco; | 6754878_Mm; | DNase | None | The G9a domain is not |
| DR1533 | 0.001; | 9e-28; | detectable in other prokaryotes. | ||
| Bacterial-eukaryotic | 171-265; | 4-148; | In eukaryotes, this domain so | ||
| McrA family | G9a domain (DNA- | far has been found only as part | |||
| endonuclease | binding?) | of multidomain nuclear proteins, | |||
| including transcription factors | |||||
| Escherichia coli | |||||
| 1787179_ | 94933_Ppu; | 3747107_Rn; | Oxidoreductase | None | The eukaryotic domain is present |
| b0947 | 3e-10; | 3e-32; | (as a partial sequence) also in the | ||
| Bacterial-eukaryotic | 287-367; | 4-261; | beta-proteobacterium Vogesella. | ||
| ferredoxin | uncharacterized | This domain contains a conserved | |||
| domain (thiol | pair of cysteines, which together | ||||
| oxidoreductase?) | with the ferredoxin fusion, may | ||||
| suggest a thiol oxidoreductase | |||||
| activity. Most of the eukaryotic | |||||
| proteins containing this domain | |||||
| appear to be mitochondrial, | |||||
| suggesting the possibility of an | |||||
| alternative evolutionary scenario | |||||
| 1787678_ | 487713_Sli; | 5459012_Pab; | Methyl-transferase/ | None | |
| b1410 | 3e-05; | 1e-17; | Lipase (exact function | ||
| Bacterial-archaeal | 408-522; | 33-274; | unclear) | ||
| SAM-dependent | lyso-phospholipase | ||||
| methyl-transferase | |||||
| 1787679_ynbD | 1591375_Mj; | 7160233_Sp; | Membrane-associated | None | An unusual case of fusion |
| Archaeal-eukaryotic | 4e-04; | 1e-06; | bifunctional | between an apparently archaeal | |
| 50-218; | 346-415; | phosphatase | and a typical eukaryotic domain | ||
| membrane-associated | tyrosine phosphatase | in a bacterium | |||
| acid phosphatase | |||||
| 1788589_ | 5763950_Sco; | 3860247_At; | Bifunctional enzyme; | None | |
| b2255 | 4e-35; | 1e-55; | exact function unclear | ||
| Bacterial-eukaryotic | 1-259; | 318-652; | |||
| methionyl-tRNA | dTDP-glucose 4-6- | ||||
| formyl-transferase | dehydratase | ||||
| 1788938_yfiQ | 929735_Nsp; | 2649370_Af; | acetyl-CoA synthetase/ | None | |
| bacterial-Archaeal/ | 8e-32; | 4e-85; | acetyl-transferase; exact | ||
| eukaryotic | 637-874; | 6-689; | function unclear | ||
| acetyl-transferase | acetyl-CoA synthetase | ||||
| Mycobacterium tuberculosis | |||||
| 2909507_ | 6469244_Sco; | 4151109_Tbr; | Adenylate cyclase/ | 7476546, | M. tuberculosis encodes three |
| Rv2488c, | 5e-64; | 6e-04; | ATPase; probable | 7476738 | paralogous proteins that consist |
| 2791528_Rv1358, | 19-603; | 6-167; | transcription regulator | of three domains, the eukaryotic- | |
| 1419061_ | 4726088_Rer; | adenylate cyclase | type adenylate cyclase, AP | ||
| Rv1358 | 2e-12; | (apoptotic) ATPase and DNA- | |||
| Bacterial-eukaryotic | 818-1073 | binding response regulator, and | |||
| two stand-alone versions of | |||||
| adenylate cyclase, which show the | |||||
| closest similarity to the cyclase | |||||
| domain of the multidomain | |||||
| proteins | |||||
| 1314025_ | 120037_Tt; | 178213_Hs; | Ferredoxin/ | 2076681 | D. radiodurans also encodes the |
| Rv0886 | 1e-11; | 4e-65; | ferredoxin reductase | eukaryotic-type ferredoxin | |
| Bacterial-eukaryotic | 2-79; | 93-543; | reductase, but the ferredoxin | ||
| ferredoxin | ferredoxin reductase | fusion is unique to mycobacteria | |||
| 3261732_ | 2661695_Sco; | 279520_Dd; | cAMP-dependent | 4455714 | |
| Rv0998 | 3e-13; | 7e-07; | acetyl-transferase(?) | (M. leprae) | |
| Bacterial-eukaryotic | 148-328; | 30-105; | |||
| acetyl-transferase | cAMP-binding domain | ||||
| 2326726_ | 421331_Cvi; | 2645721_Mm; | Bifunctional enzyme of | 1929080 | |
| Rv1683 | 1e-24; | 6e-26; | poly (3-hydroxy-butyrate) | ||
| Bacterial-eukaryotic | 23-359; | 456-972; | synthesis | ||
| poly (3-hydroxy- | very-long-chain | ||||
| butyrate) synthase | acyl-CoA synthetase | ||||
| 1403447_ | 6752338_Sco; | 3892714_At; | Polyfunctional enzyme | 2661651 | In this protein, the domain of |
| Rv2006 | 2e-27; | 8e-27; | of trehalose metabolism | apparent eukaryotic origin | |
| Bacterial-eukaryotic | 23-240; | 264-521; | is flanked by bacterial domains | ||
| phosphatase; | trehalose-6-phosphate | from both sides | |||
| 6448751_Sco; | phosphatase | ||||
| 0.0; | |||||
| 534-1320; | |||||
| trehalose hydrolase | |||||
| 2896788_ | 117648_Ec; | 3073773_Mm; | Polyfunctional enzyme | 2337823 | The presence of the stand-alone |
| Rv2051c | 1e-16; | 4e-31; | of lipid metabolism | (M. leprae); | version of the eukaryotic |
| Bacterial-eukaryotic | 94-514; | 588-829; | 6468712 | domain in Streptomyces suggests | |
| apolipoprotein | dolichol-phosphate- | (Streptomyces | an ancient horizontal transfer | ||
| N-acyltransferase | mannose synthase | coelicolor) | |||
| 2791523_ | 6225563_Scy; | 1098605_Cnu; | Multifunctional enzyme | None | |
| Rv2483c | 7e-16; | 5e-22; | of phospholipid | ||
| Bacterial-eukaryotic | 36-253; | 289-492; | metabolism | ||
| phosphoserine | 1-acyl-sn- | ||||
| phosphatase | glycerol-3-phosphate | ||||
| acyltransferase | |||||
| 2894233_ | 2633801_Bs; | 4538974_At; | Molybdopterin synthase | 2076687 | The same domain organization |
| Rv3323c | 3e-19; | 7e-06; | is seen in D. radiodurans, but in | ||
| Bacterial-eukaryotic | 89-208; | 2-82; | this case, both components | ||
| molybdopterin | molybdopterin | appear to be of bacterial origin | |||
| synthase large subunit | synthase small subunit | ||||
| (MoaE) | (MoaD) | ||||
| 2960152_ | 4753872_Sco; | 466119_Ce; | cAMP-regulated | 2501688 | M. tuberculosis encodes two |
| Rv3728, | 1e-35; | 7e-20; | efflux pump(?) | strongly similar paralogs with | |
| 7477551_ | 56-428; | 549-964; | the same domain architecture | ||
| Rv3239c | transmembrane | cAMP-binding domain- | |||
| Bacterial-eukaryotic | efflux protein | phosphoesterase | |||
| 2960153_ | 4731342_Sl; | 1591330_Mj; | Bifunctional enzyme | 1806159 | The amino-terminal domain |
| Rv3729 | 3e-14; | 3e-58; | of molybdenum | stand-alone paralog is more | |
| Bacterial-archaeal | 510-776; | molybdenum | cofactor biosynthesis | similar to archaeal homologs | |
| C5-O-methyl- | cofactor biosynthesis | than to the stand-alone paralog, | |||
| Transferase | protein MoaA | but nevertheless, the latter | |||
| (mitomycin | (Fe-S oxidoreductase) | appears to be of archaeal origin | |||
| biosynthesis) | |||||
| 3261806_ | 40487_Cg; | 7304009_Dm; | Secreted protein | 7649504 | The stand-alone version of the |
| Rv3811 | 3e-12; | 2e-12; | (S. coelicolor) | eukaryotic domain is present | |
| Bacterial-eukaryotic | 404-494; | 198-384; | only in Streptomyces | ||
| major secreted | peptidoglycan | ||||
| protein | recognition protein | ||||
| Treponema pallidum | |||||
| 3322964_ | 7225946_Nm; | 320868_Sc; | Uridine kinase | None | A co-linear ortholog is present |
| TP0667 | 9e-04; | 2e-13; | in Thermotoga | ||
| Bacterial-eukaryotic | 10-154; | 290-488; | |||
| threonyl-tRNA | uridine kinase | ||||
| synthetase (TGS and | |||||
| H3H domains) | |||||
| Thermotoga maritima | |||||
| 4981276_ | 68516_Bs; | 3218401_Sp; | Uridine kinase | None | A co-linear ortholog is present |
| TM0751 | 3e-07; | 2e-11; | in Treponema | ||
| Bacterial-eukaryotic | 11-200; | 288-475; | |||
| threonyl-tRNA | uridine kinase | ||||
| synthetase (TGS and | |||||
| H3H domains) | |||||
| Eukaryotes | |||||
| Saccharomyces cerevisiae | |||||
| 536367_ | 586134_Bt; | 7450047_Aa; | Bifunctional signal- | 5249 | SurE homologs are not |
| Ybr094w | 9e-10; | 8e-09; | transduction protein | (Yarrowia | detectable in eukaryotes other |
| Eukaryotic/ | tubulin-tyrosine ligase | acid phosphatase | lipolytica) | than yeasts | |
| Bacterial-archaeal | (SurE) | ||||
| 1431219_ | 577625_Hs; | 3328426_Ct | |||
| YDL141w | 1e-39 | 5e-27; | |||
| Eukaryotic- | Biotin-[propionyl- | biotin protein ligase | Bifunctional biotin- | None | An ortholog with an identical |
| bacterial | CoA-carboxylase(ATP- | protein ligase | domain architecture is present | ||
| hydrolysing)] ligase | in S. pombe | ||||
| 458922_ | 477096_Gg; | 1653075_Ssp; | heat shock | NONE | An ortholog with an identical |
| YHR206W | 8e-18; | 7e-17; | transcription | domain architecture is present | |
| Eukaryotic-bacterial | 78-216 | 375-503; | factor | in S. pombe (3327019) | |
| heat shock | CheY domain | ||||
| transcription factor | |||||
| domain | 2983676_Aa; | Siroheme synthase | 2330809 | S. pombe also encodes a co-linear | |
| 486539_ | 1146165_At; | 1e-04; | (S. pombe) | ortholog (3581882); apparent | |
| YKR069w | 3e-34; | 22-188; | displacement of the bacterial | ||
| Eukaryotic-bacterial | 249-556; | precorrin-2 oxidase | precorrin-2 oxidase by a distinct | ||
| urophorphyrin III | Rossmann fold domain | ||||
| methylase | |||||
| 1302305_ | 4938476_At; | 3212189_Hi; | Multifunctional enzyme | None | Co-linear orthologs in S. pombe |
| YNL256w | 5e-65; | 5e-05; | of folate biosynthesis | (7490442) and Pneumocystis | |
| Eukaryotic-bacterial | 324-861 | 62-148; | carinii (283062) | ||
| 7,8-dihydro-6- | 187-297; | ||||
| hydroxymethylpterin- | dihydro-neopterin | ||||
| pyro-phosphokinase+ | aldolase | ||||
| Dihydro-pteroate | |||||
| synthase | |||||
| 1419887_ | 7297709_Dm; | 5918510_Sco; | Bifunctional RNA | 2213559 | The known bacterial homologs |
| YOL066c | 2e-72; | 2e-10; | modification enzyme | (S. pombe) | have a two-domain organization; |
| Eukaryotic-bacterial | 42-408; | 436-574; | the evolutionary scenario could | ||
| large ribosomal | pyrimidine deaminase | have included domain | |||
| subunit pseudoU | rearrangements | ||||
| synthase | |||||
| 1419865_ | 2462827_At; | 1075360_Hi; | Transcriptional regulator None | Yeast encodes three strongly | |
| YOL055c, | 1e-39; | 6e-24; | of thiamine biosynthesis | similar paralogs with identical | |
| 2132251_ | 22-390; | 342-549; | genes(?) | domain organization; co-linear | |
| YPL258c, | phosphomethyl | transcriptional | orthologs are present in other | ||
| 2132289_ | pyrimidinekinase | activator | ascomycetes | ||
| YPR121w | (thiamine biosynthesis) | ||||
| Eukaryotic-bacterial | |||||
| 1370444_ YPL214c | 2746079_Bn; | 2648451_Af; | Bifunctional thiamine | None | Except for the one from |
| Eukaryotic-archaeal/ | 1e-27; | 9e-27; | biosynthesis enzyme | A. fulgidus, all highly conserved | |
| Bacterial | 9-233; | 251-531; | homologs of the kinase domain | ||
| thiamin-phosphate | hydroxyethyl-thiazole | of this protein are bacterial; it | |||
| pyro-phosphorylase | kinase | appears likely that the A. fulgidus | |||
| gene is the result of horizontal | |||||
| transfer |
The following complete genomes were analyzed. Archaea: Aeropyrum pernix (Ap); Archaeoglobus fulgidus (Af); Methanococcus jannaschii (Mj); Methanobacterium thermoautotrophicum (Mth); Pyrococcus horikoshii (Ph); Bacteria: Aquifex aeolicus (Aa); Borrelia burgdorferi (Bb); Bacillus subtilis (Bs); Chlamydophila pneumoniae (Cp); Deinococcus radiodurans (Dr); Escherichia coli (Ec); Haemophilus influenzae (Hi); Helicobacter pylori (Hp); Mycobacterium tuberculosis (Mt); Mycoplasma pneumoniae (Mp); Rickettsia prowazekii (Rp); Synechocystis sp (Ssp); Thermotoga maritima (Tm); Treponema pallidum (Tp). No IKFs were detected in the genomes that are not shown in the table. Additional species name abbreviations: At, Arabidopsis thaliana; Axy, Acetobacter xylinus; Bn, Brassica napus; Ce, Caenorhabditis elegans; Cvi, Chromatium vinosum; Gg, Gallus gallus; Hs, Homo sapiens; Mm, Mus musculus; Rn, Rattus norvegicus; Sco, Streptomyces coelicolor; Sl, Streptomyces lavendulae.