Table 1 Interkingdom domain fusions and their probable origins

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