Skip to main content
SpringerLink
Log in

The evolution of the thrombospondin gene family

  • Published:
Journal of Molecular Evolution Aims and scope Submit manuscript

Summary

Thrombospondin-1 is an adhesive glycoprotein that is involved in cellular attachment, spreading, migration, and proliferation. To date, four genes have been identified that encode for the members of the thrombospondin gene family. These four genes are homologous to each other in the EGF-like (type 2) repeats, the calcium-binding (type 3) motifs, and the COOH-terminal. The latter has been reported to be a cell-binding domain in thrombospondin-1. Phylogenetic trees have been constructed from the multisequence alignment of thrombospondin sequences from human, mouse, chicken, and frog. Two different algorithms generate comparable results in terms of the topology and the branch lengths. The analysis indicates that an early form of the thrombospondin gene duplicated about 925 million years ago. The gene duplication that produced the thrombospondin-1 and -2 branches of the family is predicted to have occurred 583 million years ago, whereas the gene duplication that produced the thrombospondin-3 and -4 branches of the family is predicted to have occurred 644 million years ago. These results indicate that the members of the thrombospondin gene family have existed throughout the evolution of the animal kingdom and thus probably participate in functions that are common to most of its members.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Asch AS, Tepler J, Silbiger S, Nachman RL (1991) Cellular attachment to thrombospondin: cooperative interactions between receptor systems. J Biol Chem 266:1740–1745

    Google Scholar 

  • Bisbee CA, Baker MA, Wilson AC, Hadji-Azimi I, Fischberg M (1977) Albumin phylogeny for clawed frogs (Xenopus). Science 105:785–787

    Google Scholar 

  • Bornstein P, Alfi D, Devarayala S, Framson P, Li P (1990) Characterization of the mouse thrombospondin gene and evaluation of the role of the first intron in human gene expression. J Biol Chem 265:16691–16698

    Google Scholar 

  • Bornstein P, Devarayalu S, Li P, Disteche CM, Framson P (1991b) A second thrombospondin gene in the mouse is similar in organization to thrombospondin-1 but does not respond to serum. Proc Natl Acad Sci USA 88:8636–8640

    Google Scholar 

  • Bornstein P, O'Rourke K, Wikstrom K, Wolf FW, Katz R, Li P, Dixit VM (1991a) A second, expressed thrombospondin gene (Thbs2) exists in the mouse genome. J Biol Chem 266:12821–12824

    Google Scholar 

  • Culotti JG, Spence A, Zhou Y, Scott L, Leung-Hagesteijn B, Hedgecook E (1991) Theunc-5 axon guidance gene ofC. elegans has features of a cell adhesion receptor. J Cell Biol 115(2):122a

    Google Scholar 

  • DeSimone DW, Hynes RO (1988)Xenopus laevis integrins: Structural conservation and evolutionary divergence of integrin ß subunits. J Biol Chem 263:5333–5340

    Google Scholar 

  • Dixit VM, Haverstick DM, O'Rourke KM, Hennessy SW, Grant GA, Santoro SA, Frazier WA (1985) A monoclonal antibody against human thrombospondin inhibits platelet aggregation. Proc Natl Acad Sci USA 82:3472–3476

    Google Scholar 

  • Dixit VM, Hennessy SW, Grant GA, Rotwein P, Frazier WA (1986) Characterization of a cDNA encoding the heparin and collagen binding domains of human thrombospondin. Proc Natl Acad Sci USA 83:5449–5453

    Google Scholar 

  • Engel J (1989) EGF-like domains in extracellular matrix proteins: Localized signals for growth and differentiation. FEBS Lett 251:1–7

    Google Scholar 

  • Feng D-F, Doolittle RF (1987) Progressive sequence alignment as a prerequisite to correct phylogenetic trees. J Mol Evol 25:351–360

    Google Scholar 

  • Galvin NJ, Dixit VM, O'Rourke KM, Santoro SA, Grant GA, Frazier WA (1985) Mapping of epitopes for monoclonal antibodies against human platelet thrombospondin with electron microscopy and high sensitivity amino acid sequencing. J Cell Biol 101:1434–1441

    Google Scholar 

  • Gartner TK, Walz DA, Aiken M, Starr-Spires L, Ogivie ML (1984) Antibodies against a 23kd heparin-binding fragment of thrombospondin inhibit platelet aggregation. Biochem Biophys Res Commun 124:290–295

    Google Scholar 

  • Gilbert W (1978) Why genes in pieces? Nature 271:501–503

    Google Scholar 

  • Goundis D, Reid KBM (1988) Properdin, the terminal complement components, thrombospondin and the circumsporozoite protein of malaria parasites. Nature 335:82–85

    Google Scholar 

  • Hillis DM, Bull JJ, White ME, Badgett MR, Molineux IJ (1992) Experimental phylogenetics: generation of a known phylogeny. Science 255:589–592

    Google Scholar 

  • Jaffe E, Bornstein P, Disteche CM (1990) Mapping of the thrombospondin gene to human chromosome 15 and mouse chromosome 2 byin situ hybridization. Genomics 7:123–126

    Google Scholar 

  • Kaesberg PR, Ershler WB, Esko JD, Mosher DF (1989) Chinese hamster ovary cell adhesion to human platelet thrombospondin is dependent on cell surface heparin sulfate proteoglycan. J Clin Invest 83:994–1001

    Google Scholar 

  • Kimura M (1980) A simple method for estimating evolutionary rate of base substitution. J Mol Evol 16:111–120

    Google Scholar 

  • Klar A, Baldassare M, Jessell TM (1992) F-spondin: a gene expressed at high levels in floor plate encodes a secreted protein that promotes neural cell adhesion and neurite extension. Cell 69:95–110

    Google Scholar 

  • Kobayashi S, Eden-McCutchan F, Framson P, Bornstein P (1986) Partial amino acid sequence of human thrombospondin as determined by analysis of cDNA clones: homology to malarial circumsporozoite proteins. Biochemistry 25:8418–8425

    Google Scholar 

  • Kobel HR, DuPasquier L (1986) Genetics of polyploidXenopus Trends Genet 2:310–315

    Google Scholar 

  • Kornblihtt AR, Gutman A (1988) The molecular biology of the extracellular matrix proteins. Biol Rev 63:465–507

    Google Scholar 

  • LaBell TL, McGookey-Milewicz DJ, Disteche CM, Byers PH (1992) Thrombospondin II: partial cDNA sequence, chromosome location and expression of a second member of the thrombospondin gene family in humans. Genomics 12:421–429

    Google Scholar 

  • Laherty CD, O'Rourke K, Wolf FW, Katz R, Seldin MF, Dixit VM (1992) Characterization of mouse thrombospondin 2 sequences and expression during cell growth. J Biol Chem 267:3274–3281

    Google Scholar 

  • Lawler J (1986) The structural and functional properties of thrombospondin. Blood 67:1197–1209

    Google Scholar 

  • Lawler J, Derick LH, Connolly JE, Chen JH, Chao FC (1985) The structure of human platelet thrombospondin. J Biol Chem 260:3762–3772

    Google Scholar 

  • Lawler J, Simons E (1983) Cooperative binding of calcium to thrombospondin: the effect of calcium on the circular dichroism and limited tryptic digestion of thrombospondin. J Biol Chem 258:12098–12101

    Google Scholar 

  • Lawler J, Duquette M, Ferro P (1991) Cloning and sequencing of chicken thrombospondin. J Biol Chem 266:8039–8043

    Google Scholar 

  • Lawler J, Duquette M, Ferro P, Copeland NG, Gilbert DJ, Jenkins NA (1991) Characterization of the murine thrombospondin gene. Genomics 11:587–600

    Google Scholar 

  • Lawler J, Ferro P, Duquette M (1992) Expression and mutagenesis of thrombospondin. Biochemistry 31:1173–1180

    Google Scholar 

  • Lawler J, Hynes RO (1986) The structure of human thrombospondin, and adhesive glycoprotein with multiple calcium-binding sites and homologies with several different proteins. J Cell Biol 103:1635–1648

    Google Scholar 

  • Lawler J, Weinstein R, Hynes RO (1988) Cell attachment to thrombospondin: the role of Arg-Gly-Asp, calcium and integrin receptors. J Cell Biol 107:2351–2361

    Google Scholar 

  • Murphy-Ullrich JE, Hook M (1989) Thrombospondin modulates focal adhesions in endothelial cells. J Cell Biol 109:1309–1319

    Google Scholar 

  • Patthy L (1988) Detecting distant homologies of mosaic proteins: analysis of the sequences of thrombomodulin, thrombospondin, complement components C9, C8a, C8b, vitronectin and plasma cell membrane glycoprotein PC-1. J Mol Biol 202: 689–696

    Google Scholar 

  • Pratter CA, Plotkin J, Jaye D, Frazier WA (1991) The properdinlike type 1 repeats of human thrombospondin contain a cell attachment site. J Cell Biol 112:1031–1040

    Google Scholar 

  • Rich KA, George FW IV, Law JL, Martin WJ (1990) Cell-adhesive motif in region 11 of malarial circumsporozoite protein. Science 249:1574–1577

    Google Scholar 

  • Robson KJH, Hall JRS, Jennings MW, Harris TJR, Marsh K, Newbold CI, Tate VE, Wetherall DV (1988) A highly conserved amino acid sequence in thrombospondin, properdin and in proteins from sporozoites and blood stages of a human malaria parasite. Nature 335:79–82

    Google Scholar 

  • Sanger F, Nicklen S, Coulson AR (1977) DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci USA 74: 5463–5467

    Google Scholar 

  • Schonbaum CP, Organ EL, Qu S, Cavener DR (1992) The Drosophila melanogaster stranded at second (SAS) gene encodes a putative epidermal cell surface receptor required for larval development. Dev Biol 151:431–445

    Google Scholar 

  • Smith TF, Waterman MS (1981) Comparison of biosequences. Adv Applied Math 2:482–189

    Google Scholar 

  • Smith TF, Srinivasan A, Schochetman G, Marcus M, Myers G (1988) The phylogenetic history of immunodeficiency viruses. Nature 333:573–575

    Google Scholar 

  • Smith RF, Smith TF (1990) Automatic generation of primary sequence patterns from sets of related protein sequences. Proc Natl Acad Sci USA 87:118–122

    Google Scholar 

  • Smith RF, Smith TF (1992) Pattern-induced multi-sequence alignment (PIMA) algorithm employing secondary structure-dependent gap penalties for use in comparative protein modelling. Prot Enginee 5:35–41

    Google Scholar 

  • Sun X, Mosher DF, Rapraeger A (1989) Heparin sulfate-mediated binding of epithelial cell surface proteoglycan to thrombospondin. J Biol Chem 264:2885–2889

    Google Scholar 

  • Swofford DL (1990) Phylogenetic analysis using parsimony. Illinois Natural History Survey, Champaign

    Google Scholar 

  • Taraboletti G, Roberts D, Liotta LA, Giavazzi R (1990) Platelet thrombospondin modulates endothelial cell adhesion, mobility and growth: a potential angiogenesis regulatory factor. J Cell Biol 111:765–772

    Google Scholar 

  • Tuszynski GP, Karczewski J, Smith L, Murphy A, Rothman VL, Knudsen KA (1989) The GPIIb-IIIa-like complex may function as a human melanoma cell adhesion receptor for thrombospondin. Exp Cell Res 182:473–481

    Google Scholar 

  • Tuszynski GP, Rothman VL, Deutch AH, Hamilton BK, Eyal J (1992) Biological activities of peptides and peptide analogues derived from common sequences present in thrombospondin, properdin and malarial proteins. J Cell Biol 116:209–217

    Google Scholar 

  • Urry LA, Ramos J, Duquette M, DeSimone DW, Lawler J (1991) Cloning, characterization and expression of thrombospondin inXenopus laevis embryos. J Cell Biol 115(2):295a

    Google Scholar 

  • Vos HL, Devarayalu S, de Vries Y, Bornstein P (1992) Thrombospondin-3 (Thbs3), a new member of the thrombospondin gene family. J Biol Chem 267:12192–12196

    Google Scholar 

  • Wilson AC, Carlson SS, White TJ (1977) Biochemical evolution. Ann Rev Biochem 46:573–639

    Google Scholar 

  • Wolf FW, Eddy RL, Shows TB, Dixit VM (1990) Structure and chromosomal localization of the human thrombospondin gene. Genomics 6:685–691

    Google Scholar 

  • Yabkowitz R, Dixit VM (1991) Human carcinoma cells express receptors for distinct domains of thrombospondin. Can Res 51:1645–1650

    Google Scholar 

Download references

Author information

Author notes

  1. Lisa Urry

    Present address: Department of Biology, Tufts University, Packard Avenue, 02155, Medford, MA, USA

Authors and Affiliations

  1. The Vascular Research Division, Department of Pathology, Brigham and Women's Hospital and Harvard Medical School, LMRC-Room 414, 221 Longwood Avenue, 02115, Boston, MA, USA

    Jack Lawler, Mark Duquette, Lisa Urry & Katherine McHenry

  2. Biomolecular Engineering Research Center, Boston University, 36 Cummington St., 02215, Boston, MA, USA

    Temple F. Smith

Authors
  1. Jack Lawler
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Mark Duquette
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Lisa Urry
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Katherine McHenry
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Temple F. Smith
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

About this article

Cite this article

Lawler, J., Duquette, M., Urry, L. et al. The evolution of the thrombospondin gene family. J Mol Evol 36, 509–516 (1993). https://doi.org/10.1007/BF00556355

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF00556355

Key words

Search

Navigation