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Evolution of the mannose-binding lectin gene in primates

Abstract

The mannose-binding lectin MBL2 plays an important role in the innate immune system. It binds carbohydrates surface, acts as an opsonin and activates the complement system. With the aim of studying the evolution of the MBL2 gene in primates, we sequenced its coding region in 12 non-human primate species and compared them with the human sequence. We demonstrated that nucleotide and amino-acidic sequences of the MBL2 among primates are highly homologous, underlining the importance of this molecule in the defense system against pathogen invasions. In particular, in the collagen-like domain that confers the characteristic structure to MBL2 protein, the identity among primates is really high. In the carbohydrate recognition domain, we evidenced some primates' group-specific amino-acidic mutations not resulting in changes of the structure or function of this MBL2 domain. Phylogenetic analysis did not evidence any positive selective pressure in MBL2 gene among non-human primates. Our findings indicate that MBL2 is well conserved in agreement with its important role in the immune system: in non-human primates, we did not observe the same ‘plasticity’ of the MBL2 human gene, where a frequency of more than 1% of nucleotide variations was described in the coding and promoter regions.

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References

  1. Kuhlman M, Joiner K, Ezekowitz RA . The human mannose-binding protein functions as an opsonin. J Exp Med 1989; 169: 1733–1745.

    Article  CAS  Google Scholar 

  2. Hajela K, Kojima M, Ambrus G et al. The biological functions of MBL-associated serine proteases (MASPs). Immunobiology 2002; 205: 467–475.

    Article  CAS  Google Scholar 

  3. Petersen SV, Thiel S, Jensenius JC . The mannose-binding lectin pathway of complement activation: biology and disease association. Mol Immunol 2001; 38: 133–149.

    Article  CAS  Google Scholar 

  4. Turner MW, Hamvas RM . Mannose-binding lectin: structure, function, genetics and disease associations. Rev Immunogenet 2000; 2: 305–322.

    CAS  Google Scholar 

  5. Garred P, Larsen F, Madsen HO, Koch C . Mannose-binding lectin deficiency-revisited. Mol Immunol 2003; 40: 73–84.

    Article  CAS  Google Scholar 

  6. Larsen F, Madesn HO, Sim RB, Koch C, Garred P . Disease-associated mutations in human mannose-binding lectin compromise oligomerization and activity of the final protein. J Biol Chem 2004; 279: 21302–21311.

    Article  CAS  Google Scholar 

  7. Garred P, Thiel S, Madsen HO, Ryder LP, Jensenius JC, Svejgaard A . Gene frequency and partial protein characterization of an allelic variant of mannan binding protein associated with low serum concentrations. Clin Exp Immunol 1992; 90: 517–521.

    Article  CAS  Google Scholar 

  8. Garred P, Madsen HO, Kurtzhals JA et al. Diallelic polymorphism may explain variations of the blood concentration of mannose-binding protein in Eskimos, but not in black Africans. Eur J Immunogenet 1992; 19: 403–412.

    Article  CAS  Google Scholar 

  9. Bernig T, Taylor JG, Foster CB, Staats B, Yeager M, Chanock SJ . Sequence analysis of the mannose-binding lectin (MBL2) gene reveals a high degree of heterozygosity with evidence of selection. Genes Immun 2004; 5: 461–476.

    Article  CAS  Google Scholar 

  10. Garred P, Madsen HO, Balslev U et al. Susceptibility to HIV infection and progression of AIDS in relation to variant alleles of mannose-binding lectin. Lancet 1997; 349: 236–240.

    Article  CAS  Google Scholar 

  11. Madsen HO, Garred P, Thiel S et al. Interplay between promoter and structural gene variants control basal serum level of mannan-binding protein. J Immunol 1995; 155: 3013–3020.

    CAS  Google Scholar 

  12. Koch A, Melbye M, Sorensen P et al. Acute respiratory tract infections and mannose-binding lectin insufficiency during early childhood. JAMA 2001; 285: 1316–1321.

    Article  CAS  Google Scholar 

  13. Garred PM, Strom J, Quist L, Taaning E, Madsen HO . Association of mannose-binding lectin polymorphisms with sepsis and fatal outcome, in patients with systemic inflammatory response syndrome. J Infect Dis 2003; 188: 1394–1403.

    Article  CAS  Google Scholar 

  14. Garred P, Madsen HO, Halberg P et al. Mannose-binding lectin polymorphisms and susceptibility to infection in systemic lupus erythematosus. Arthritis Rheum 1999; 42: 2145–2152.

    Article  CAS  Google Scholar 

  15. Jacobsen S, Madsen HO, Klarlund M et al. The influence of mannose binding lectin polymorphisms on disease outcome in early polyarthritis. J Rheumatol 2001; 28: 935–942.

    CAS  Google Scholar 

  16. Glockner FO, Kube M, Bauer M et al. Complete genome sequence of the marine planctomycete Pirelulla sp. Strain 1. Proc Natl Acad Sci USA 2003; 100: 8298–8303.

    Article  CAS  Google Scholar 

  17. Holmskov U, Holt P, Reid KB, Willis AC, Teisner B, Jensenius JC . Purification and characterization of bovine mannan-binding protein. Glycobiology 1993; 3: 147–153.

    Article  CAS  Google Scholar 

  18. Storgaard P, Nielsen EH, Andersen O et al. Isolation and characterization of porcine mannan-binding proteins of different size and ultrastructure. Scand J Immunol 1996; 43: 289–296.

    Article  CAS  Google Scholar 

  19. Kozutsumi Y, Kawasaki T, Yamashina I . Isolation and characterization of mannan-binding protein from rabbit serum. Biochem Biophys Res Commun 1980; 95: 658–664.

    Article  CAS  Google Scholar 

  20. Sastry K, Zahedi K, Lelias JM, Whitehead AS, Ezekowitz RA . Molecular characterization of the mouse mannose-binding proteins. The mannose-binding protein A but not C is an acute phase reactant. J Immunol 1991; 147: 692–697.

    CAS  PubMed  Google Scholar 

  21. Oka S, Ikeda K, Kawasaki T, Yamashina I . Isolation and characterization of two distinct mannan-binding proteins from rat serum. Arch Biochem Biophys 1988; 260: 257–266.

    Article  CAS  Google Scholar 

  22. Laursen SB, Dalgaard TS, Thiel S et al. Coning and sequencing of a cDNA encoding chicken mannose-binding lectin (MBL) and comparison with mammalian analogues. Immunology 1998; 93: 421–430.

    Article  CAS  Google Scholar 

  23. Vitved L, Holmskov U, Koch C, Teisner B, Hansen S, Skjodt K . The homologue of mannose-binding lectin in the carp family Cyprinidae is expressed at high level in spleen, and the deduced primary structure predicts affinity for galactose. Immunogenetics 2000; 51: 955–964.

    Article  CAS  Google Scholar 

  24. Nair SV, Pearce S, Green PL, Mahajan D, Newton RA, Raftos DA . A collectin-like protein from tunicates. Comp Biochem Physiol B Biochem Mol Biol 2000; 125: 279–289.

    Article  CAS  Google Scholar 

  25. Kurata H, Sannoh T, Kozutsumi Y, Yokota Y, Kawasaki T . Structure and function of mannose-binding proteins isolated from human liver and serum. J Biochem 1994; 115: 1148–1154.

    Article  CAS  Google Scholar 

  26. Wallis R, Shaw JM, Uitdehaag J, Chen CB, Torgersen D, Drickamer K . Localization of the serine protease-binding sites in the collagen-like domain of mannose-binding protein. J Biol Chem 2004; 279: 14065–14073.

    Article  CAS  Google Scholar 

  27. Del Pero M, Boniotto M, Zuccon D et al. Defensin 1 gene variability among non-human primates. Immunogenetics 2002; 53: 907–913.

    Article  CAS  Google Scholar 

  28. Boniotto M, Tossi A, Del Pero M et al. Evolution of beta defensin 2 gene in primates. Genes Immun 2003; 4: 251–257.

    Article  CAS  Google Scholar 

  29. Aiyar A . The use of CLUSTAL W and CLUSTAL X for multiple sequence alignment. Methods Mol Biol 2000; 132: 221–241.

    CAS  Google Scholar 

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

    CAS  Google Scholar 

  31. Kumar S, Tamura K, Jakobsen IB, Nei M . MEGA2: molecular evolutionary genetics analysis software. Bioinformatics 2001; 17: 1244–1245.

    Article  CAS  Google Scholar 

  32. Kimura M . Preponderance of synonymous changes as evidence for the neutral theory of molecular evolution. Nature 1977; 267: 275–276.

    Article  CAS  Google Scholar 

  33. Hughes AL, Nei M . Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals over-dominant selection. Nature 1988; 335: 167–170.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported by an MIUR grant COFIN 2003. Maria Vittoria Verga Falzacappa is recipient of a long-term fellowship from the University of Trieste. We thank Dr S Vellayan and the animal keepers of the Zoo Negara Malaysia (Kuala Lumpur) for their great help in the collection of non-human primates' biological samples.

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Correspondence to M V Verga Falzacappa.

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Verga Falzacappa, M., Segat, L., Puppini, B. et al. Evolution of the mannose-binding lectin gene in primates. Genes Immun 5, 653–661 (2004). https://doi.org/10.1038/sj.gene.6364140

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