Supplementary Information

Table 1. Catalogue of homologs to immune-related genes in Chinese amphioxus.

ID Similarity to Species Accession no. Function Genes may be involved in rearrangement 1132 /RAG cohort 1 Homo sapiens AAH53343.1 V(D)J recombination, of 2806 recombination activating gene 1 Mus musculus NP_033083.1 Putatively involved in activation and expression gene activation, recombination of recombination activation genes (RAGs). activating gene 1 inducing Genes of immunoglobulin superfamily 2234 Variable region-containing Branchiostoma AAN62910.1 IgSF like protein chitin-binding protein 4 floridae 2372 T cell receptor V delta 2 Rattus norvegicus AF196201_1 IgSF like protein Genes controlling lymphocyte ontogeny 1367 Max dimerization protein Mus musculus NP_034881.1 another basic helix-loop-helix protein that binds to MYC and is required for its function.

1368 max interacting protein 1 Rattus norvegicus NP_037292.1 HLH protein that binds to MYC 1809 receptor protein Notch1 Cynops BAC 41349.1 a receptor for membrane bound ligands, and may pyrrhogaster play multiple roles during development

2890 MYC PROTEIN (C-MYC) pir; Homo sapiens Q17103 v-myc myelocytomatosis viral related oncogene, neuroblastoma derived 3767 Myb-like DNA-binding domain Mus musculus BAB22140.1 Regulate the expression of CD34,CD13, c-myc, containing protein cdc2, CD4,TCR 898 ETS homologue Strongylocentrotus AAA30048.1 Transcription factor purpuratus 4966 early B-cell factor 3; Olf-1/EBF-like Mus musculus NP_034226.1 early B-cell development 2 6151 Myc homolog Crassostrea AAB34577.1 Expression of the c-myc, produces an oncogenic virginica transcription factor, is regulated in normal cells but is frequently deregulated in human cancers.

6296 interferon regulatory factor 2 Homo sapiens AAH15803 inhibits the IRF1-mediated transcriptional activation of interferons alpha and beta

6655 Notch homolog protein sea squirt T30201 as a receptor for membrane bound ligands, and (Halocynthia may play multiple roles during development roretzi) Genes involved in lymphocyte signaling 25 CD63 antigen; melanoma 1 antigen Mus musculus NP_031679.1 Tetraspanin receptors, participation in cell migration and adhesion 354 casein kinase I alpha LS Gallus gallus AAB96334.1 cell surface receptor linked signal transduction ID Similarity to Species Accession no. Function 525 RAN_BRARE GTP-BINDING Danio rerio P79735 GTP-binding protein NUCLEAR PROTEIN 535 Activated protein kinase C receptor Rattus norvegicus A36986 PRKC-mediated signaling (RACK1) 1187 ras homolog gene family, member Homo sapiens NP_001655.1 Rho protein signal transduction A; GTP-binding protein 1206 mitogen-activated protein kinase Homo sapiens NP_002749.2 mitogen-activated protein (MAP) kinase kinase kinase 6 isoform 1 1600 ADP-ribosylation factor-like 2 Homo sapiens AAH02530 small GTP-binding proteins of the RAS superfamily 1857 Protein tyrosine phosphatase IVA1 Homo sapiens NP_003454.1 Protein tyrosine phosphatase 2195 Leukocyte surface antigen CD53 Mus musculus NP_031677.1 transduction of CD2-generated signals in T cells and natural killer cells 2236 tumor necrosis factor alpha induced Mus musculus NP_033424.1 Hyaluronan-binding protein protein 6 2368 Tumor necrosis factor Homo sapiens AAD24202 intracellular trafficking receptor-associated factor 4(TRAF4)-associated factor 2 2723 tumor necrosis factor alpha induced Mus musculus NP_033424.1 Hyaluronan-binding protein protein 6 4229 mitogen activated protein kinase Mus musculus NP_035970.1 growth factor stimulated cell proliferation and kinase 5 muscle cell differentiation.

4530 CD3 associated protein; antisense Homo sapiens AF017633_1 T-cell activation to ERCC-1 (CAST) 5104 Casein kinase II, alpha chain Homo sapiens P21868 Actin binding 5404 mitogen-activated protein kinase 10 Homo sapiens NP_002744.1 plays regulatory roles in the signaling pathways isoform 1 during neuronal apoptosis 5661 TNF receptor associated factor 3 Mus musculus AAC52175.1 a critical component of the lymphotoxin-beta (CD40 receptor associated factor 1) receptor (LTbetaR) signaling complex

5977 B cell phosphoinositide 3-kinase Petromyzon AAN64296.2 Links BCR-associated kinases with adaptor (BCAP) marinus phosphatidylinositol 3-kinase 6024 pre-B-cell colony-enhancing factor Suberites CAB65409.1 up-regulated in activated lymphocytes, domuncula nicotinamide phosphoribosyltransferase

6570 LPS-induced TNF-alpha factor Mus musculus NP_064364.1 small integral of lysosome/late endosome 6827 kangai 1,CD82 antigen Rattus norvegicus NP_113985.1 metastasis suppressor Genes required for lymphocyte proliferation and migration 1492 CD81 antigen (target of Rattus norvegicus NP_037219.1 Tetraspanin receptors, participation in cell antiproliferative antibody 1) migration and adhesion 3308 CD9 antigen Sus scrofa Q8WMQ3 Tetraspanin receptors, participation in cell migration and adhesion Genes involving in antigen processing and ID Similarity to Species Accession no. Function presentation 221 proteasome (prosome, macropain) Mus musculus NP_036098.1 Protein degradation subunit, alpha type 6, PSMA6 484 HLA-B-associated transcript 1A Homo sapiens AAB94615.1 DEAD protein family of ATP-dependent RNA helicases 512 ribosome associated membrane Homo sapiens AAH29067.1 Controls glycosylation of MHC class protein 4 II-associated invariant chain 676 proteasome (prosome, macropain) Homo sapiens AAP88811.1 Protein degradation subunit, beta type, 6 PSMB6 972 interferon gamma inducible; Mus musculus NP_075552.1 MHC class II-restricted antigen processing lysosomal thiol reductase protein 30 988 allograft inflammatory factor 1 Suberites CAC38780.1 ionized calcium binding adapter domuncula 1082 calreticulin Mus musculus NP_031617.1 major Ca(2+)-binding (storage) protein 1100 proteosome PSMB5/8 protein Branchiostoma AAL74417.1 Protein degradation lanceolatum 1467 nuclear factor of kappa light Mus musculus NP_035039.1 unknown, Lies in MHC class I region polypeptide gene enhancer in B-cells inhibitor-like 1 1628 proteasome (prosome, macropain) Homo sapiens AAH00509 Protein degradation subunit, beta type, 7 , PSMB7 2255 cathepsin L Sus scrofa CAC44793.1 Cysteine protease 2438 Cathepsin B precursor Araneus AAP59456.1 Cysteine protease ventricosus 2776 cathepsin Z Mus musculus CAB44494.1 Cysteine protease 3311 HLA class II region expressed gene Homo sapiens NP_055075.1 chaperone activity, Lies in MHC region KE2 3316 cathepsin D Apriona germari AF454831_1 Cysteine protease 3349 heat shock protein hsp70-related Homo sapiens NP_057383.1 Chaperone protein 4667 source of immunodominant Homo sapiens AAL71884.1 oligosaccharyl transferase activity MHC-associated peptides 5021 IK cytokine, down-regulator of HLA Mus musculus XP_128899.1 down-regulate HLA II molecular II 5552 novel protein similar to Danio rerio CAD54662.1 Lies in MHC region hydroxysteroid (17-beta) dehydrogenase 8, RING2 (KE6) 6292 ABC-C transporter Homo sapiens CAA65825.1 ABC transporter 6935 HLA-B associated transcript 5 Homo sapiens NP_066983 involved in some aspects of immunity. Other immune-related genes 190 peptidylprolyl isomerase-like 1 Mus musculus NP_081121.1 Binds cyclosporin A 839 chaperonin containing TCP1, Homo sapiens NP_006420.1 chaperone activity ID Similarity to Species Accession no. Function subunit 7 (eta); chaperonin containing t-complex polypeptide 1, eta subunit 840 chaperonin-containing T-complex Danio rerio AF506229_1 chaperone activity protein 1 zeta subunit 873 90 kDa heat-shock protein Homo sapiens CAA33259.1 Chaperone 1613 macrophage migration inhibitory Amblyomma AF126688_1 Regulation of macrophage function in factor americanum inflammation 1930 peptidylprolyl isomerase-like 3; Mus musculus NP_081627.1 Binds cyclosporin A cyclophilin-like 3 2586 mature T-cell proliferation 1 Mus musculus NP_034969.1 mature T cell proliferation 2813 mitogen-activated protein-binding Mus musculus NP_112538.1 late endosomal/lysosomal MP1 interacting protein-interacting protein protein 3086 T-complex protein 1, zeta subunit Oryctolagus AAC19379.1 chaperone activity, cytoplasm (TCP-1-zeta) (CCT-zeta) cuniculus 3245 DnaJ (Hsp40) homolog, subfamily Mus musculus NP_032324.1 Chaperone A, member 1 3297 dnaK-type molecular chaperone Dictyostelium S37394 Chaperone hsc70 discoideum 3555 peptidyl prolyl isomerase H; Homo sapiens NP_006338.1 Binds cyclosporin A cyclophilin H 3905 basic, immunoglobulin-like variable Strongylocentrotus AF411391_1 immunoglobulin-like variable motif-containing motif-containing protein purpuratus protein 4462 TGF-beta receptor binding protein Mus musculus XP_216619.1 translation initiation factor activity

5132 ferritin Branchiostoma AAN77903.1 Iron storage and cellular regulation belcheri 5445 Chaperone protein dnaK Porphyromonas BAA35087.1 Chaperone gingivalis 5709 Alpha-2-macroglobulin Mus musculus NP_783327.1 protease inhibitor and cytokine transporter

5748 paired box protein Pax-2 beta Branchiostoma AAC12734.1 critical regulators that specify the nephric isoform floridae lineage. 6160 B lymphocyte cell adhesion Mus musculus AF102134_1 cell adhesion molecule activity molecule, CD22 antigen 6232 dendritic cells-lysosome associated Mus musculus CAD52824.1 provides selectins with carbohydrate ligands membrane glycoprotein 6779 Thioredoxin Branchiostoma AAK72483.1 Redox reactions, augments expression of IL-2 belcheri receptor 7056 natural killer cell enhancement Oncorhynchus AF250193_1 Immunoregulation of natural killer cell activity factor mykiss 242 Peptidyl-prolyl cis-trans isomerase Drosophila AAB03701.1 Binds cyclosporin A melanogaster Adhesion molecules ID Similarity to Species Accession no. Function 2115 cadherin 1 Danio rerio NP_571895.1 calcium dependent cell-cell adhesion glycoprotein 2668 E-selectin Equus caballus AF307972_1 Adhesion molecules participate in the interaction between leukocytes and the endothelium

4643 cell adhesion molecule RST Drosophila virilis AF419620_1 homophilic cell adhesion 6637 similar to protocadherin LKC Homo sapiens XP_193722.1 calcium dependent cell-cell adhesion precursor glycoprotein Apoptosis related genes 324 programmed cell death 10; TF-1 cell Mus musculus NP_062719.1 Apoptosis related apoptosis related protein-15 1461 baculoviral IAP repeat-containing 5; Mus musculus NP_033819.1 cysteine protease inhibitor activity;apoptosis urviving; apoptosis inhibitor 4 inhibitor activity 1900 requiem; ubi-d4; apoptosis response Homo sapiens NP_006259.1 transcription factor for apoptotic response; zinc finger protein regulator in hematopoietic cell growth and turnover. 1907 cytotoxic granule-associated Homo sapiens NP_071320.1 possesses nucleolytic activity against cytotoxic RNA-binding protein lymphocyte (CTL) target cells

2651 FAS-associated factor 1 isoform b Homo sapiens NP_572051.1 binds to FAS antigen and can initiate apoptosis

3791 Fas apoptotic inhibitory molecule Mus musculus BAB24225.1 Apoptosis related 4050 apoptotic chromatin condensation Mus musculus BAB28171.1 regulation of HSP 27 transcription; estrogen inducer receptor corepressor 4410 programmed cell death 4 (neoplastic Homo sapiens AAH26104.1 involved in protein-protein interactions in transformation inhibitor) eukaryotic translation regulators other CD molecules 24 CD163 antigen; Homo sapiens NP_004235.2 scavenger receptor activity macrophage-associate 47 B cell antigen CD75, CD76 antigen Homo sapiens CAA38246.1 humoral immune response; regulate galectin-1-induced CD45 clustering, phosphatase modulation, and T cell death 1961 L-type amino acid transporter1 Homo sapiens NP_003477.2 neutral amino acid transporter activity (CD98 light chain) (Integral membrane 2233 CD2 homolog African swine NP_042752 regulation of striated muscle contraction fever virus 2364 stabilin 2; CD44-like precursor Homo sapiens NP_060034.8 fasciclin-like adhesion; FELL hyaluronan receptor for endocytosis 5709 similar to CD109; Homo sapiens XP_050563.2 alpha(2) macroglobulin;endopeptidase inhibitor alpha-2-macroglobulin activity 5738 CD5 antigen-like precursor Mus musculus Q9QWK4 scavenger receptor, cellular defense response

6174 CD49e; CD51 Homo sapiens P08648 integrin-mediated signaling pathway cell Mus musculus NP 032428 1 adhesion receptor activity ID Similarity to Species Accession no. Function Mus musculus NP_032428.1 adhesion receptor activity

6384 Ectonucleoside triphosphate Mus musculus AAB81014.1 G-protein coupled receptor protein signaling diphosphohydrolase 2; CD39 pathway;magnesium ion binding antigen-like 1 6592 platelet glycoprotein V; CD42D; Rattus norvegicus NP_036927.1 cell adhesion; blood coagulation