SupplementaryMaterial 2

List of DFI organisms (Total 74). The sequences were retrieved from GenBank by BLAST search (Supplementary Material 1), initially using T. gondiiFCBP protein sequence as query, but later other DFI sequences were also used in order to identify all sequences with various degrees of similarity. This list is not meant to be exhaustive, as new organisms continue to be discovered and more genomes are sequenced. Over time, several organisms were reclassified and renamed, underscoring the novelty and exotic nature of the organisms. Only for a few, randomly selected organisms, we have also listed the single immunophilin sequences (CYN or FKBP) found in their genome, which shows that there is no relation between the presence of a DFI gene and the presence of CYN and FKBP genes.

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SpeciesDomain structureAccession #Phylogeny Number of single CYNs and FKBPs (and domain information)

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Phylum Apicomplexa

Babesia bigeminaFKBP-TPR-CYNXP_012768359.1Apicomplexa0 FKBP, 9 CYN (CeCYN16, SYF2, Ubox RING, WD40)

Babesia bovis T2BoFKBP-TPR-CYNXP_001608690.1Apicomplexa0 FKBP, 9 CYN (Ubox, WD40)

Babesia microti RIFKBP-TPR-CYNXP_012648744.1Apicomplexa

Eimeria brunettiFKBP-TPR-CYNCDJ53046.1Apicomplexa

Eimeria maximaFKBP-TPR-CYNXP_013335079.1Apicomplexa

Eimeria tenella FKBP-TPR-CYNAET50588.1Apicomplexa2 FKBP, 11 CYN (SYF2, WD40, ZnF-NOSIP)

Hammondia hammondiFKBP-TPR-CYNXP_008888049.1Apicomplexa2 FKBP, 12 CYN (CeCYN16, RING, WD40)

Neospora caninumFKBP-TPR-CYNXP_003883131.1Apicomplexa

Theileria equiFKBP-TPR-CYNXP_004832922.1Apicomplexa

Theileria parvaFKBP-TPR-CYNXP_765469.1Apicomplexa0 FKBP, 9 CYN (RING, WD40)

Toxoplasma gondii(3 strains)FKBP-TPR-CYNAAX51680.1Apicomplexa2 FKBP, 13 CYN (CeCYN16, RING, SYF2, WD40)

Phylum Spirochaetes

Borrelia hermsii DAH CYN-FKBPWP_012422177.1Spirochaetes

Treponema caldaria CYN-FKBPWP_013967678.1Spirochaetes

DSM 7334

Spirochaeta Africana CYN-FKBPWP_014456714.1Spirochaetes 2 CYN, 1 FKBP

Spirochaeta sp. BuddyCYN-FKBP WP_013608701.1Spirochaetes

Spirochaeta coccoides CYN-FKBP WP_013740452.1Spirochaetes

DSM 17374

Spirochaeta lutea CYN-FKBPWP_037548329.1 Spirochete 0 CYN, 1 FKBP

Treponema azotonutricium CYN-FKBPWP_015710234.1Spirochaetes

ZAS-9

Treponema brennaborenseCYN-FKBPWP_013757191.1Spirochaetes

DSM 12168

Treponema denticolaCYN-FKBPWP_002680321.1Spirochaetes0 CYN, 1 FKBP

Treponema primitiaCYN-FKBPWP_015709565.1Spirochaetes0 CYN, 2 FKBP

ZAS-2

Treponema putidumCYN-FKBPWP_044979872.1Spirochaetes

Treponema succinifaciens CYN-FKBPWP_013700291.1Spirochaetes

DSM 2489

Treponema vincentii CYN-FKBPWP_006188840.1Spirochaetes0 CYN, 1 FKBP

ATCC 35580

Phylum Bacteroidetes (mostly Flavobacteria)

Aquimarina agarivoransCYN-FKBPWP_010523173.1Flavobacteria

Aequorivita sp. D-24CYN-FKBPWP_062622682.1Flavobacteria

Capnocytophaga canimorsusCYN-FKBPWP_013997216.1Flavobacteria

Cc5

Capnocytophaga canimorsusCYN-FKBPWP_013997324.1Flavobacteria

Cc5

Capnocytophaga CYN-FKBPWP_002665439.1Flavobacteria

gingivalis ATCC 33624

Capnocytophaga CYN-FKBPWP_002667121.1Flavobacteria

gingivalis ATCC 33624

Capnocytophaga sputigena CYN-FKBP WP_002679844.1Flavobacteria1 CYN, 0 FKBP

Capno

Capnocytophaga ochracea CYN-FKBP WP_015782565.1Flavobacteria0 CYN, 0 FKBP

F0287

Capnocytophaga sp. oralCYN-FKBP WP_009411812.1Flavobacteria

taxon 324

Capnocytophaga sp. oralCYN-FKBP WP_009411339.1Flavobacteria

taxon 324

Cellulophaga algicolaCYN-FKBPWP_013551507.1Flavobacteria

DSM 14237

Cellulophaga algicolaCYN-FKBPWP_013549201.1Flavobacteria

DSM 14237

Cellulophaga lyticaCYN-FKBPWP_013619851.1Flavobacteria

DSM 7489

Chryseobacterium gleumCYN-FKBP WP_002980016.1Flavobacteria0 CYN, 2 FKBP

ATCC 35910

Croceibacter atlanticusCYN-FKBP WP_013187883.1Flavobacteria2 CYN, 1 FKBP

Dokdonia donghaensisCYN-FKBPWP_021778660.1Flavobacteria

multiple strains

Flavobacteria bacterium CYN-FKBPEAZ96145.1 Flavobacteria0 CYN, 0 FKBP

Flavobacteria bacteriumCYN-FKBPWP_006795114.1Flavobacteria

BBFL7

Flavobacteriales bacterium CYN-FKBPWP_013306554.1Flavobacteria

HTCC2170

Flavobacterium chungangenseCYN-FKBPWP_031454950.1 Flavobacteria 0 CYN, 1 FKBP

Flavobacterium daejeonenseCYN-FKBPWP_055090896.1 Flavobacteria 0 CYN, 0 FKBP

Flavobacterium frigoris CYN-FKBPWP_007137991.1Flavobacteria 0 CYN, 1 FKBP

Flavobacterium hibernum CYN-FKBPWP_041519349.1 Flavobacteria 0 CYN, 1 FKBP

Flavobacterium hydatis CYN-FKBPWP_035626885.1Flavobacteria 0 CYN, 3 FKBP

Flavobacterium johnsoniaeCYN-FKBPAAM92026Flavobacteria0 CYN, 2 FKBP

Flavobacterium johnsoniaeCYN-FKBPAAM92027Flavobacteria0 CYN, 2 FKBP

Flavobacterium psychrophilumCYN-FKBPYP_001296758.1 Flavobacteria0 CYN, 0 FKBP

JIP02/86

Flavobacterium psychrophilumCYN-FKBPYP_001296759.1 Flavobacteria0 CYN, 0 FKBP

JIP02/86

Flavobacterium reichenbachiiCYN-FKBPWP_035684065.1Flavobacteria 0 CYN, 0 FKBP

Flavobacterium seoulenseCYN-FKBPWP_035658288.1 Flavobacteria 0 CYN, 1 FKBP

Flavobacterium succinicans CYN-FKBPWP_024981134.1Flavobacteria 0 CYN, 1 FKBP

Fluviicola taffensis CYN-FKBPWP_013686748.1Flavobacteria

DSM 16823

Gaetbulibacter saemankumensis CYN-FKBPWP_027136884.1Flavobacteria 1 CYN, 2 FKBP

Gelidibacter mesophilusCYN-FKBPWP_027126492.1 Flavobacteria 1 CYN, 2 FKBP

Gramella forsetiiCYN-FKBPCAL65762 Flavobacteria1 CYN, 2 FKBP

Gramella forsetiiCYN-FKBPWP_011710397.1Flavobacteria1 CYN, 2 FKBP

Gramella echinicola CYN-FKBPWP_026933765.1Flavobacteria 1 CYN, 1 FKBP

Kordia algicida OT-1CYN-FKBPWP_007093789.1Flavobacteria1 CYN, 1 FKBP

Lacinutrix sp.CYN-FKBPWP_013870480.1Flavobacteria

5H-3-7-4

Leeuwenhoekiella blandensisCYN-FKBPWP_009781285.1Flavobacteria1 CYN, ~6 FKBP

Leeuwenhoekiella palythoaeCYN-FKBPWP_072983594.1Flavobacteria

Leeuwenhoekiella marinoflavaCYN-FKBPWP_073099465.1Flavobacteria

Mesoflavibacter zeaxanthinifaciensCYN-FKBPWP_010517508.1Flavobacteria 2 CYN, 3 FKBP

Nonlabens marinusCYN-FKBPWP_041496246.1Flavobacteria1 CYN, 1 FKBP

Nonlabens ulvanivoransCYN-FKBPGAL75631.1Flavobacteria

Polaribacter dokdonensisCYN-FKBPWP_053975013.1Flavobacteria 2 CYN, 1 FKBP

Polaribacter irgensii CYN-FKBPWP_004570747.1Flavobacteria 0 CYN, 4 FKBP

Psychroflexus torquis CYN-FKBPAFU67563.1Flavobacteria 1 CYN, 1 FKBP

Psychroserpens damuponensis CYN-FKBPWP_040278254.1Flavobacteria 1 CYN, 0 FKBP

Riemerella anatipestiferCYN-FKBPWP_013446672.1Flavobacteria

DSM 15868

Riemerella anatipestiferCYN-FKBPEFT35731.1Flavobacteria

RA-YM

Robiginitalea biformataCYN-FKBPWP_015754216.1Flavobacteria

Robiginitalea biformataCYN-FKBPWP_015755540.1Flavobacteria

HTCC2501

Salinimicrobium catenaCYN-FKBPSDL76680.1Flavobacteria

Sediminicola spCYN-FKBPWP_062055259.1 Flavobacteria 1 CYN, ~2 FKBP

Tamlana nanhaiensis CYN-FKBPWP_044625819.1 Flavobacteria 1 CYN, 2 FKBP

Tenacibaculum ovolyticum CYN-FKBPWP_028889491.1Flavobacteria 0 CYN, 3 FKBP

Tenacibaculum sp. CYN-FKBPWP_028891023.1Flavobacteria 0 CYN, 8 FKBP

Ulvibacter litoralisCYN-FKBPSDE92800.1Flavobacteria

Weeksella virosaCYN-FKBP WP_013598693.1Flavobacteria

DSM 16922

Winogradskyella spCYN-FKBPWP_045468090.1Flavobacteria 2 CYN, 0 FKBP

Zobellia galactanivoransCYN-FKBPWP_013994175.1Flavobacteria

Zobellia galactanivoransCYN-FKBPWP_013995030.1Flavobacteria

Zunongwangia mangroviCYN-FKBPSFC62278.1Flavobacteria

Zunongwangia profundaCYN-FKBPWP_013071163.1Flavobacteria1 CYN, 2 FKBP

SM-A87

Zunongwangia profunda CYN-FKBPWP_013070348.1Flavobacteria

SM-A87

Superphylum Heterokonta

Albugo candidaFKBP-TPR-CYNCCI40768.1Oomycetes

Albugo laibachiiFKBP-TPR-CYNCCA14206.1Oomycete

Phytophthora infestansFKBP-TPR-CYNXP_002906896.1Oomycetes5 FKBP (EF hand, TPR), 21 CYN (RRM, U-box, WD40)

Phytophthora parasitica FKBP-TPR-CYNETK71084.1Oomycetes

Phytophthora sojaeFKBP-TPR-CYNXP_009516060.1Oomycetes Similar to P. infestans

Plasmopara halstediiFKBP-TPR-CYNCEG39850.1Oomycetes

Saprolegnia diclinaFKBP-TPR-CYNXP_008614859.1Oomycetes

Aphanomyces invadans FKBP-TPR-CYNXP_008864835.1Oomycetes

Others

Candidatus Ruthia magnificaCYN-FKBPWP_011737713.1γ-proteobacteria1 CYN, 0 FKBP

Candidatus ThioglobusCYN-FKBPWP_053820422.1γ-proteobacteria1 CYN, 0 FKBP

Desulfotalea psychrophilaCYN-FKBPWP_011188886.1Proteobacteria0 CYN, 1 FKBP

Desulfobulbus propionicus CYN-FKBP WP_015723644.1Proteobacteria

DSM 2032

Ichthyophthirius multifiliisFKBP-TPR-CYNXP_004031957.1Ciliophora

Oxytricha trifallaxFKBP-TPR-CYNEJY68739.1Ciliophora

Paramecium tetraureliaFKBP-TPR-CYNXP_001444554.1Ciliophora

Paramecium tetraureliaFKBP-TPR-CYNXP_001445268.1Ciliophora

Perkinsus marinusFKBP-TPR-CYNXP_002768449.1Dinoflagellate

Phaeodactylum tricornutumFKBP-TPR-CYNXP_002184174.1Diatom

Pseudocohnilembus persalinusFKBP-TPR-CYNKRX10096.1Ciliophora

Stylonychia lemnaeFKBP-TPR-CYNCDW88109.1Ciliophora

Tetrahymena thermophilaFli-ATPase-FKBP-TPR-CYN XP_976669.2Ciliophora

Thalassiosira oceanicaFKBP-TPR-CYNXP_002286257.1Diatom

Thalassiosira pseudonanaFKBP-TPR-CYNXP_002286257.1Diatom

*Uncultured archaeonFKBP-CYNAAU82569 Archea?

GZfos18C8

*Uncultured archaeonFKBP-CYNCAI64202Archea?

GZfos18C8

Unidentified eubacteriumCYN-FKBPEDM43472.1Eubacteria?

SCB49

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*The genome of this single uncultured and tentatively characterized archaea, code-named GZfos18C8, contained two FCBP sequences, both lacking TPR. These two paralogs are highly similar to each other, with 85% amino acid identity, the major difference being the lack of 12-residue peptide sequence in one of them. According to PRED-SIGNAL, which predicts archaeal signal peptides with Hidden Markov Model, both proteins contain nearly identical signal peptides at the N-terminus (Reliability score >0.9, a perfect score being 1.0). These two FCBP paralogs possibly have a common but uncertain origin. We have ignored these two sequences in the rest of the paper, and until more definitive archaeal examples are found, we will maintain that the DFIs are absent in archaea.