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Molecular characterization of the immune system: emergence of proteins, processes, and domains

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Abstract

Many genes and proteins are required to carry out the processes of innate and adaptive immunity. For many studies, including systems biology, it is necessary to have a clear and comprehensive definition of the immune system, including the genes and proteins that take part in immunological processes. We have identified and cataloged a large portion of the human immunology-related genes, which we call the essential immunome. The 847 identified genes and proteins were annotated, and their chromosomal localizations were compared to the mouse genome. Relation to disease was also taken into account. We identified numerous pseudogenes, many of which are expressed, and found two putative new genes. We also carried out an evolutionary analysis of immune processes based on gene orthologs to gain an overview of the evolutionary past and molecular present of the human immune system. A list of genes and proteins were compiled. A comprehensive characterization of the member genes and proteins, including the corresponding pseudogenes is presented. Immunome genes were found to have three types of emergence in independent studies of their ontologies, domains, and functions.

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References

  • Abbas AR, Baldwin D, Ma Y, Ouyang W, Gurney A, Martin F, Fong S, van Lookeren Campagne M, Godowski P, Williams PM, Chan AC, Clark HF (2005) Immune response in silico (IRIS): immune-specific genes identified from a compendium of microarray expression data. Genes Immun 6:319–331

    Article  PubMed  CAS  Google Scholar 

  • Aderem A, Smith KD (2004) A systems approach to dissecting immunity and inflammation. Semin Immunol 16:55–67

    Article  PubMed  CAS  Google Scholar 

  • Arakawa H, Buerstedde JM (2004) Immunoglobulin gene conversion: insights from bursal B cells and the DT40 cell line. Dev Dyn 229:458–464

    Article  PubMed  CAS  Google Scholar 

  • Ashburner M, Ball CA, Blake JA, Botstein D, Butler H, Cherry JM, Davis AP, Dolinski K, Dwight SS, Eppig JT, Harris MA, Hill DP, Issel-Tarver L, Kasarskis A, Lewis S, Matese JC, Richardson JE, Ringwald M, Rubin GM, Sherlock G (2000) Gene ontology: tool for the unification of biology. The Gene Ontology Consortium. Nat Genet 25:25–29

    Article  PubMed  CAS  Google Scholar 

  • Ausubel FM (2005) Are innate immune signaling pathways in plants and animals conserved? Nat Immunol 6:973–979

    Article  PubMed  CAS  Google Scholar 

  • Balakirev ES, Ayala FJ (2003) Pseudogenes: are they “junk” or functional DNA? Annu Rev Genet 37:123–151

    Article  PubMed  CAS  Google Scholar 

  • Burge C, Karlin S (1997) Prediction of complete gene structures in human genomic DNA. J Mol Biol 268:78–94

    Article  PubMed  CAS  Google Scholar 

  • Caenepeel S, Charydczak G, Sudarsanam S, Hunter T, Manning G (2004) The mouse kinome: discovery and comparative genomics of all mouse protein kinases. Proc Natl Acad Sci USA 101:11707–11712

    Article  PubMed  CAS  Google Scholar 

  • Carrington M (2003) The KIR gene cluster. National Library of Medicine U.S. National Center for Biotechnology Information, Bethesda

    Google Scholar 

  • Chen F, Mackey AJ, Stoeckert CJ Jr, Roos DS (2006) OrthoMCL–DB: querying a comprehensive multi-species collection of ortholog groups. Nucleic Acids Res 34:D363–D368

    Article  PubMed  CAS  Google Scholar 

  • Cunchillos C, Lecointre G (2003) Evolution of amino acid metabolism inferred through cladistic analysis. J Biol Chem 278:47960–47970

    Article  PubMed  CAS  Google Scholar 

  • De Tomaso AW, Nyholm SV, Palmeri KJ, Ishizuka KJ, Ludington WB, Mitchel K, Weissman IL (2005) Isolation and characterization of a protochordate histocompatibility locus. Nature 438:454–459

    Article  PubMed  CAS  Google Scholar 

  • Du Pasquier L (2004) Innate immunity in early chordates and the appearance of adaptive immunity. C R Biol 327:591–601

    Article  PubMed  CAS  Google Scholar 

  • Eason DD, Cannon JP, Haire RN, Rast JP, Ostrov DA, Litman GW (2004) Mechanisms of antigen receptor evolution. Semin Immunol 16:215–226

    Article  PubMed  CAS  Google Scholar 

  • Feolo M, Helmberg W, Sherry S, Maglott DR (2000) NCBI genetic resources supporting immunogenetic research. Rev Immunogenet 2:461–467

    PubMed  CAS  Google Scholar 

  • Friedman R, Hughes AL (2002) Molecular evolution of the NF–κB signaling system. Immunogenetics 53:964–974

    Article  PubMed  CAS  Google Scholar 

  • Harrison PM, Gerstein M (2002) Studying genomes through the aeons: protein families, pseudogenes and proteome evolution. J Mol Biol 318:1155–1174

    Article  PubMed  CAS  Google Scholar 

  • Harrison PM, Hegyi H, Balasubramanian S, Luscombe NM, Bertone P, Echols N, Johnson T, Gerstein M (2002) Molecular fossils in the human genome: identification and analysis of the pseudogenes in chromosomes 21 and 22. Genome Res 12:272–280

    Article  PubMed  CAS  Google Scholar 

  • Huising MO, Stet RJ, Savelkoul HF, Verburg-van Kemenade BM (2004) The molecular evolution of the interleukin-1 family of cytokines; IL-18 in teleost fish. Dev Comp Immunol 28:395–413

    Article  PubMed  CAS  Google Scholar 

  • Hurst LD (2002) The Ka/Ks ratio: diagnosing the form of sequence evolution. Trends Genet 18:486

    Article  PubMed  Google Scholar 

  • Hutton JJ, Jegga AG, Kong S, Gupta A, Ebert C, Williams S, Katz JD, Aronow BJ (2004) Microarray and comparative genomics-based identification of genes and gene regulatory regions of the mouse immune system. BMC Genomics 5:82

    Article  PubMed  CAS  Google Scholar 

  • Hyatt G, Melamed R, Park R, Seguritan R, Laplace C, Poirot L, Zucchelli S, Obst R, Matos M, Venanzi E, Goldrath A, Nguyen L, Luckey J, Yamagata T, Herman A, Jacobs J, Mathis D, Benoist C (2006) Gene expression microarrays: glimpses of the immunological genome. Nat Immunol 7:686–691

    Article  PubMed  CAS  Google Scholar 

  • Janeway CA, Travers P (2001) Immunobiology. Garland, New York

    Google Scholar 

  • Kasahara M, Suzuki T, Pasquier LD (2004) On the origins of the adaptive immune system: novel insights from invertebrates and cold-blooded vertebrates. Trends Immunol 25:105–111

    Article  PubMed  CAS  Google Scholar 

  • Kelley J, de Bono B, Trowsdale J (2005) IRIS: a database surveying known human immune system genes. Genomics 85:503–511

    Article  PubMed  CAS  Google Scholar 

  • Khalturin K, Bosch TC (2007) Self/nonself discrimination at the basis of chordate evolution: limits on molecular conservation. Curr Opin Immunol 19:4–9

    Google Scholar 

  • Krause CD, Pestka S (2005) Evolution of the class 2 cytokines and receptors, and discovery of new friends and relatives. Pharmacol Ther 106:299–346

    Article  PubMed  CAS  Google Scholar 

  • Lee Y, Sultana R, Pertea G, Cho J, Karamycheva S, Tsai J, Parvizi B, Cheung F, Antonescu V, White J, Holt I, Liang F, Quackenbush J (2002) Cross-referencing eukaryotic genomes: TIGR orthologous gene alignments (TOGA). Genome Res 12:493–502

    Article  PubMed  CAS  Google Scholar 

  • Lefranc MP, Giudicelli V, Ginestoux C, Bosc N, Folch G, Guiraudou D, Jabado-Michaloud J, Magris S, Scaviner D, Thouvenin V, Combres K, Girod D, Jeanjean S, Protat C, Yousfi-Monod M, Duprat E, Kaas Q, Pommie C, Chaume D, Lefranc G (2004) IMGT—ontology for immunogenetics and immunoinformatics. In Silico Biol 4:17–29

    PubMed  CAS  Google Scholar 

  • Litman GW, Cannon JP, Dishaw LJ (2005) Reconstructing immune phylogeny: new perspectives. Nat Rev Immunol 5:866–879

    Article  PubMed  CAS  Google Scholar 

  • Marchalonis JJ, Schluter SF (1994) Development of an immune system. In: Beck G (ed) Primordial immunity: foundations for the vertebrate immune system. New York Academy of Sciences, New York, pp 1–12

    Google Scholar 

  • Menezes H, Jared C (2002) Immunity in plants and animals: common ends through different means using similar tools. Comp Biochem Physiol C Toxicol Pharmacol 132:1–7

    Article  PubMed  Google Scholar 

  • Miller MM, Wang C, Parisini E, Coletta RD, Goto RM, Lee SY, Barral DC, Townes M, Roura-Mir C, Ford HL, Brenner MB, Dascher CC (2005) Characterization of two avian MHC-like genes reveals an ancient origin of the CD1 family. Proc Natl Acad Sci USA 102:8674–8679

    Article  PubMed  CAS  Google Scholar 

  • Nei M, Gojobori T (1986) Simple methods for estimating the numbers of synonymous and nonsynonymous nucleotide substitutions. Mol Biol Evol 3:418–426

    PubMed  CAS  Google Scholar 

  • Nicholas HR, Hodgkin J (2004) Responses to infection and possible recognition strategies in the innate immune system of Caenorhabditis elegans. Mol Immunol 41:479–493

    Article  PubMed  CAS  Google Scholar 

  • Nonaka M, Kimura A (2006) Genomic view of the evolution of the complement system. Immunogenetics 58:701–713

    Article  PubMed  CAS  Google Scholar 

  • Nonaka M, Yoshizaki F (2004) Evolution of the complement system. Mol Immunol 40:897–902

    Article  PubMed  CAS  Google Scholar 

  • Ollila J, Vihinen M (2003) Stimulation-induced gene expression in Ramos B-cells. Genes Immun 4:343–350

    Article  PubMed  CAS  Google Scholar 

  • Parra G, Blanco E, Guigo R (2000) GeneID in Drosophila. Genome Res 10:511–515

    Article  PubMed  CAS  Google Scholar 

  • Pearson WR (2000) Flexible sequence similarity searching with the FASTA3 program package. Methods Mol Biol 132:185–219

    PubMed  CAS  Google Scholar 

  • Pederson T (1999) The immunome. Mol Immunol 36:1127–1128

    Article  PubMed  CAS  Google Scholar 

  • Piirilä H, Väliaho J, Vihinen M (2006) Immunodeficiency mutation databases (IDbases). Human Mutat 27:1200–1208

    Article  CAS  Google Scholar 

  • Remm M, Storm CE, Sonnhammer EL (2001) Automatic clustering of orthologs and in-paralogs from pairwise species comparisons. J Mol Biol 314:1041–1052

    Article  PubMed  CAS  Google Scholar 

  • Rinkevich B (2004) Primitive immune systems: are your ways my ways? Immunol Rev 198:25–35

    Article  PubMed  Google Scholar 

  • Rodgers JR, Cook RG (2005) MHC class Ib molecules bridge innate and acquired immunity. Nat Rev Immunol 5:459–471

    Article  PubMed  CAS  Google Scholar 

  • Royet J (2004) Infectious non-self recognition in invertebrates: lessons from Drosophila and other insect models. Mol Immunol 41:1063–1075

    Article  PubMed  CAS  Google Scholar 

  • Scherf M, Klingenhoff A, Werner T (2000) Highly specific localization of promoter regions in large genomic sequences by PromoterInspector: a novel context analysis approach. J Mol Biol 297:599–606

    Article  PubMed  CAS  Google Scholar 

  • Schulenburg H, Kurz CL, Ewbank JJ (2004) Evolution of the innate immune system: the worm perspective. Immunol Rev 198:36–58

    Article  PubMed  CAS  Google Scholar 

  • Smit AFA, Hubley R, Green P (1996–2004) RepeatMasker open-3.0

  • Smith LC (2001) The complement system in sea urchins. In: Beck G (ed) Phylogenetic perspectives on the vertebrate immune system. Springer, Berlin Heidelberg New York, pp 363–372

    Google Scholar 

  • Smith KD, Bolouri H (2005) Dissecting innate immune responses with the tools of systems biology. Curr Opin Immunol 17:49–54

    Article  PubMed  CAS  Google Scholar 

  • Stajich JE, Block D, Boulez K, Brenner SE, Chervitz SA, Dagdigian C, Fuellen G, Gilbert JG, Korf I, Lapp H, Lehväslaiho H, Matsalla C, Mungall CJ, Osborne BI, Pocock MR, Schattner P, Senger M, Stein LD, Stupka E, Wilkinson MD et al (2002) The Bioperl toolkit: perl modules for the life sciences. Genome Res 12:1611–1618

    Article  PubMed  CAS  Google Scholar 

  • Staudt LM, Brown PO (2000) Genomic views of the immune system*. Annu Rev Immunol 18:829–859

    Article  PubMed  CAS  Google Scholar 

  • Swofford DL (2003) PAUP*. Phylogenetic analysis using parsimony (*and other methods). Sinauer Associates, Sunderland, Massachusetts

    Google Scholar 

  • Trowsdale J, Parham P (2004) Mini-review: defense strategies and immunity-related genes. Eur J Immunol 34:7–17

    Article  PubMed  CAS  Google Scholar 

  • Väliaho J, Pusa M, Ylinen T, Vihinen M (2002) IDR: the ImmunoDeficiency resource. Nucleic Acids Res 30:232–234

    Article  PubMed  Google Scholar 

  • Vargas-Madrazo E, Almagro JC, Lara-Ochoa F (1995) Structural repertoire in VH pseudogenes of immunoglobulins: comparison with human germline genes and human amino acid sequences. J Mol Biol 246:74–81

    Article  PubMed  CAS  Google Scholar 

  • Vetvicka V, Sima P (1998) Evolutionary mechanisms of defense reactions. Birkhuser, Basel

    Google Scholar 

  • Vihinen M, Arredondo-Vega FX, Casanova JL, Etzioni A, Giliani S, Hammarström L, Hershfield MS, Heyworth PG, Hsu AP, Lähdesmäki A, Lappalainen I, Notarangelo LD, Puck JM, Reith W, Roos D, Schumacher RF, Schwarz K, Vezzoni P, Villa A, Väliaho J et al (2001) Primary immunodeficiency mutation databases. Adv Genet 43:103–188

    PubMed  CAS  Google Scholar 

  • Yamaoka K, Saharinen P, Pesu M, Holt VE III, Silvennoinen O, O’Shea JJ (2004) The Janus kinases (Jaks). Genome Biol 5:253

    Article  PubMed  Google Scholar 

  • Yang S, Doolittle RF, Bourne PE (2005) Phylogeny determined by protein domain content. Proc Natl Acad Sci USA 102:373–378

    Article  PubMed  CAS  Google Scholar 

  • Zhang Z, Harrison P, Gerstein M (2002) Identification and analysis of over 2000 ribosomal protein pseudogenes in the human genome. Genome Res 12:1466–1482

    Article  PubMed  CAS  Google Scholar 

  • Zhang Z, Harrison PM, Liu Y, Gerstein M (2003) Millions of years of evolution preserved: a comprehensive catalog of the processed pseudogenes in the human genome. Genome Res 13:2541–2558

    Article  PubMed  CAS  Google Scholar 

  • Zola H, Swart B, Nicholson I, Aasted B, Bensussan A, Boumsell L, Buckley C, Clark G, Drbal K, Engel P, Hart D, Horejsi V, Isacke C, Macardle P, Malavasi F, Mason D, Olive D, Saalmueller A, Schlossman SF, Schwartz-Albiez R et al (2005) CD molecules 2005: human cell differentiation molecules. Blood 106:3123–3126

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

We thank Martti Tolvanen for sharing with us his expertise on the content of immunome list, and Kathryn Rannikko for her help in collecting and handling the immunome data. We also thank the Medical Research Fund of Tampere University Hospital and the CAMKIN Research Network of the European Commission for the financial support.

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Correspondence to Mauno Vihinen.

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Ortutay, C., Siermala, M. & Vihinen, M. Molecular characterization of the immune system: emergence of proteins, processes, and domains. Immunogenetics 59, 333–348 (2007). https://doi.org/10.1007/s00251-007-0191-0

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