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.

Wolf et al. Genome Biology 2000 1:research0013.1   doi:10.1186/gb-2000-1-6-research0013