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High degree of conservation of the multigene tryptase locus over the past 150–200 million years of mammalian evolution

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Abstract

Activated mast cells release a number of potent inflammatory mediators including histamine, proteoglycans, cytokines, and serine proteases. The proteases constitute the majority of the mast cell granule proteins, and they belong to either the chymase or the tryptase family. In mammals, these enzymes are encoded by two different loci, the mast cell chymase and the multigene tryptase loci. In mice and humans, a relatively large number of tryptic enzymes are encoded from the latter locus. These enzymes can be grouped into two subfamilies, the group 1 tryptases, with primarily membrane-anchored enzymes, and the group 2 tryptases, consisting of the soluble mast cell tryptases. In order to study the appearance of these enzymes during vertebrate evolution, we have analyzed the dog, cattle, opossum, and platypus genomes and sought orthologues in the genomes of several bird, frog, and fish species as well. Our results show that the overall structure and the number of genes within this locus have been well conserved from marsupial to placental mammals. In addition, two relatively distantly related group 2 tryptase genes and several direct homologues of some of the group 1 genes are present in the genome of the platypus, a monotreme. However, no direct homologues of the individual genes of either group 1 or 2 enzymes were identified in bird, amphibian, or fish genomes. Our results indicate that the individual genes within the multigene tryptase locus, in their present form, are essentially mammal-specific.

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Abbreviations

aa:

Amino acid

mMCP:

Mouse mast cell protease

nt:

Nucleotide

Sim.:

Similar to

corr:

Corrected

SP:

Serine protease

hypo. pr.:

Hypothetical protein

References

  • Bhagwandin VJ, Hau LW, Mallen-St Clair J, Wolters PJ, Caughey GH (2003) Structure and activity of human pancreasin, a novel tryptic serine peptidase expressed primarily by the pancreas. J Biol Chem 278:3363–3371

    Article  CAS  PubMed  Google Scholar 

  • Caughey GH (2004) Genetic insights into mast cell chymase and tryptase function. Clin Exp All Rev 4:96–101

    Article  CAS  Google Scholar 

  • Caughey GH, Raymond WW, Blount JL, Hau LW, Pallaoro M, Wolters PJ, Verghese GM (2000) Characterization of human gamma-tryptases, novel members of the chromosome 16p mast cell tryptase and prostasin gene families. J Immunol 164:6566–6575

    CAS  PubMed  Google Scholar 

  • Daniels RJ, Peden JF, Lloyd C, Horsley SW, Clark K, Tufarelli C, Kearney L, Buckle VJ, Doggett NA, Flint J, Higgs DR (2001) Sequence, structure and pathology of the fully annotated terminal 2 Mb of the short arm of human chromosome 16. Hum Mol Genet 10:339–352

    Article  CAS  PubMed  Google Scholar 

  • Echtenacher B, Mannel DN, Hultner L (1996) Critical protective role of mast cells in a model of acute septic peritonitis. Nature 381:75–77

    Article  CAS  PubMed  Google Scholar 

  • Fajardo I, Pejler G (2003) Formation of active monomers from tetrameric human beta-tryptase. Biochem J 369:603–610

    Article  CAS  PubMed  Google Scholar 

  • Gallwitz M, Hellman L (2006) Rapid lineage-specific diversification of the mast cell chymase locus during mammalian evolution. Immunogenetics 58:641–654

    Article  CAS  PubMed  Google Scholar 

  • Gallwitz M, Reimer JM, Hellman L (2006) Expansion of the mast cell chymase locus over the past 200 million years of mammalian evolution. Immunogenetics 58:655–669

    Article  PubMed  Google Scholar 

  • Gallwitz M, Enoksson M, Hellman L (2007) Expression profile of novel members of the rat mast cell protease (rMCP)-2 and (rMCP)-8 families, and functional analyses of mouse mast cell protease (mMCP)-8. Immunogenetics 59:391–405

    Article  CAS  PubMed  Google Scholar 

  • Hallgren J, Karlson U, Poorafshar M, Hellman L, Pejler G (2000) Mechanism for activation of mouse mast cell tryptase: dependence on heparin and acidic pH for formation of active tetramers of mouse mast cell protease 6. Biochemistry 39:13068–13077

    Article  CAS  PubMed  Google Scholar 

  • Hallgren J, Spillmann D, Pejler G (2001) Structural requirements and mechanism for heparin-induced activation of a recombinant mouse mast cell tryptase, mouse mast cell protease-6: formation of active tryptase monomers in the presence of low molecular weight heparin. J Biol Chem 276:42774–42781

    Article  CAS  PubMed  Google Scholar 

  • Hallgren J, Backstrom S, Estrada S, Thuveson M, Pejler G (2004) Histidines are critical for heparin-dependent activation of mast cell tryptase. J Immunol 173:1868–1875

    CAS  PubMed  Google Scholar 

  • Hooper JD, Nicol DL, Dickinson JL, Eyre HJ, Scarman AL, Normyle JF, Stuttgen MA, Douglas ML, Loveland KA, Sutherland GR, Antalis TM (1999) Testisin, a new human serine proteinase expressed by premeiotic testicular germ cells and lost in testicular germ cell tumors. Cancer Res 59:3199–3205

    CAS  PubMed  Google Scholar 

  • Hooper JD, Bowen N, Marshall H, Cullen LM, Sood R, Daniels R, Stuttgen MA, Normyle JF, Higgs DR, Kastner DL, Ogbourne SM, Pera MF, Jazwinska EC, Antalis TM (2000) Localization, expression and genomic structure of the gene encoding the human serine protease testisin. Biochim Biophys Acta 1492:63–71

    CAS  PubMed  Google Scholar 

  • Huang C, Li L, Krilis SA, Chanasyk K, Tang Y, Li Z, Hunt JE, Stevens RL (1999) Human tryptases alpha and beta/II are functionally distinct due, in part, to a single amino acid difference in one of the surface loops that forms the substrate-binding cleft. J Biol Chem 274:19670–19676

    Article  CAS  PubMed  Google Scholar 

  • Inoue M, Isobe M, Itoyama T, Kido H (1999) Structural analysis of esp-1 gene (PRSS 21). Biochem Biophys Res Commun 266:564–568

    Article  CAS  PubMed  Google Scholar 

  • Knight PA, Wright SH, Lawrence CE, Paterson YY, Miller HR (2000) Delayed expulsion of the nematode Trichinella spiralis in mice lacking the mucosal mast cell-specific granule chymase, mouse mast cell protease-1. J Exp Med 192:1849–1856

    Article  CAS  PubMed  Google Scholar 

  • O’Sullivan CM, Liu SY, Rancourt SL, Rancourt DE (2001a) Regulation of the strypsin-related proteinase ISP2 by progesterone in endometrial gland epithelium during implantation in mice. Reproduction 122:235–244

    Article  Google Scholar 

  • O’Sullivan CM, Rancourt SL, Liu SY, Rancourt DE (2001b) A novel murine tryptase involved in blastocyst hatching and outgrowth. Reproduction 122:61–71

    Article  Google Scholar 

  • Pallaoro M, Gambacurta A, Fiorucci L, Mignogna G, Barra D, Ascoli F (1996) cDNA cloning and primary structure of tryptase from bovine mast cells, and evidence for the expression of bovine pancreatic trypsin inhibitor mRNA in the same cells. Eur J Biochem 237:100–105

    Article  CAS  PubMed  Google Scholar 

  • Pallaoro M, Fejzo MS, Shayesteh L, Blount JL, Caughey GH (1999) Characterization of genes encoding known and novel human mast cell tryptases on chromosome 16p13.3. J Biol Chem 274:3355–3362

    Article  CAS  PubMed  Google Scholar 

  • Pereira PJ, Bergner A, Macedo-Ribeiro S, Huber R, Matschiner G, Fritz H, Sommerhoff CP, Bode W (1998) Human beta-tryptase is a ring-like tetramer with active sites facing a central pore. Nature 392:306–311

    Article  CAS  PubMed  Google Scholar 

  • Raymond WW, Sommerhoff CP, Caughey GH (2005) Mastin is a gelatinolytic mast cell peptidase resembling a mini-proteasome. Arch Biochem Biophys 435:311–322

    Article  CAS  PubMed  Google Scholar 

  • Sakai K, Ren S, Schwartz LB (1996) A novel heparin-dependent processing pathway for human tryptase. Autocatalysis followed by activation with dipeptidyl peptidase I. J Clin Invest 97:988–995

    Article  CAS  PubMed  Google Scholar 

  • Sato M, Yoshida S, Iida K, Tomozawa T, Kido H, Yamashita M (2003) A novel influenza A virus activating enzyme from porcine lung: purification and characterization. Biol Chem 384:219–227

    Article  CAS  PubMed  Google Scholar 

  • Shaw-Smith CJ, Coffey AJ, Leversha M, Freeman TC, Bentley DR, Walters JR (2000) Characterisation of a novel murine intestinal serine protease. DISP. Biochim Biophys Acta 1490:131–136

    CAS  PubMed  Google Scholar 

  • Tang L, Rancourt DE (2005) Murine implantation serine proteinases 1 and 2: structure, function and evolution. Gene 364:30–36

    Article  CAS  PubMed  Google Scholar 

  • Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) The CLUSTAL_X windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25:4876–4882

    Article  CAS  PubMed  Google Scholar 

  • Trivedi NN, Tong Q, Raman K, Bhagwandin VJ, Caughey GH (2007) Mast cell alpha and beta tryptases changed rapidly during primate speciation and evolved from gamma-like transmembrane peptidases in ancestral vertebrates. J Immunol 179:6072–6079

    CAS  PubMed  Google Scholar 

  • Trivedi NN, Raymond WW, Caughey GH (2008) Chimerism, point mutation, and truncation dramatically transformed mast cell delta tryptases during primate evolution. J Allergy Clin Immunol 121:1262–1268

    Article  CAS  PubMed  Google Scholar 

  • Vanderslice P, Craik CS, Nadel JA, Caughey GH (1989) Molecular cloning of dog mast cell tryptase and a related protease: structural evidence of a unique mode of serine protease activation. Biochemistry 28:4148–4155

    Article  CAS  PubMed  Google Scholar 

  • Vernersson M, Ledin A, Johansson J, Hellman L (2002) Generation of therapeutic antibody responses against IgE through vaccination. Faseb J 16:875–877

    CAS  PubMed  Google Scholar 

  • Vernersson M, Aveskogh M, Hellman L (2004) Cloning of IgE from the echidna (Tachyglossus aculeatus) and a comparative analysis of epsilon chains from all three extant mammalian lineages. Dev Comp Immunol 28:61–75

    Article  CAS  PubMed  Google Scholar 

  • Wang HW, McNeil HP, Husain A, Liu K, Tedla N, Thomas PS, Raftery M, King GC, Cai ZY, Hunt JE (2002) Delta tryptase is expressed in multiple human tissues, and a recombinant form has proteolytic activity. J Immunol 169:5145–5152

    PubMed  Google Scholar 

  • Wernersson S, Reimer JM, Poorafshar M, Karlson U, Wermenstam N, Bengten E, Wilson M, Pilstrom L, Hellman L (2006) Granzyme-like sequences in bony fish shed light on the emergence of hematopoietic serine proteases during vertebrate evolution. Dev Comp Immunol 30:901–918

    Article  CAS  PubMed  Google Scholar 

  • Wong GW, Tang Y, Feyfant E, Sali A, Li L, Li Y, Huang C, Friend DS, Krilis SA, Stevens RL (1999) Identification of a new member of the tryptase family of mouse and human mast cell proteases which possesses a novel COOH-terminal hydrophobic extension. J Biol Chem 274:30784–30793

    Article  CAS  PubMed  Google Scholar 

  • Wong GW, Yasuda S, Madhusudhan MS, Li L, Yang Y, Krilis SA, Sali A, Stevens RL (2001) Human tryptase epsilon (PRSS22), a new member of the chromosome 16p13.3 family of human serine proteases expressed in airway epithelial cells. J Biol Chem 276:49169–49182

    Article  CAS  PubMed  Google Scholar 

  • Wong GW, Yasuda S, Morokawa N, Li L, Stevens RL (2004) Mouse chromosome 17A3.3 contains 13 genes that encode functional tryptic-like serine proteases with distinct tissue and cell expression patterns. J Biol Chem 279:2438–2452

    Article  CAS  PubMed  Google Scholar 

  • Yezzi MJ, Hsieh IE, Caughey GH (1994) Mast cell and neutrophil expression of dog mast cell protease-3. A novel tryptase-related serine protease. J Immunol 152:3064–3072

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

This investigation was supported by grants from the Swedish Natural Sciences Research Council (VR-NT) and grant RR-014214 from the US National Institutes of Health (PBS). We would also like to thank Michael Thorpe for linguistic revision and valuable comments on the manuscript.

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Author notes

  1. Jenny M. Reimer

    Present address: , Isconova AB, 751 83, Uppsala, Sweden

Authors and Affiliations

  1. Department of Cell and Molecular Biology, Program for Immunology, Uppsala University, Uppsala, Sweden

    Jenny M. Reimer & Lars Hellman

  2. Department of Veterinary Integrative Biosciences, Texas A&M University, College Station, TX, USA

    Paul B. Samollow

  3. Department of Cell and Molecular Biology, University of Uppsala, The Biomedical Center, Box 596, 751 24, Uppsala, Sweden

    Lars Hellman

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  1. Jenny M. Reimer
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Correspondence to Lars Hellman.

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Reimer, J.M., Samollow, P.B. & Hellman, L. High degree of conservation of the multigene tryptase locus over the past 150–200 million years of mammalian evolution. Immunogenetics 62, 369–382 (2010). https://doi.org/10.1007/s00251-010-0443-2

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  • DOI: https://doi.org/10.1007/s00251-010-0443-2

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