Glycoconjugate Journal

, Volume 15, Issue 2, pp 115–130 | Cite as

NetOglyc: Prediction of mucin type O-glycosylation sites based on sequence context and surface accessibility

  • Jan E Hansen
  • Ole Lund
  • Niels Tolstrup
  • Andrew A Gooley
  • Keith L Williams
  • Søren Brunak
Article

Abstract

The specificities of the UDP-GalNAc:polypeptide N-acetylgalactosaminyltransferases which link the carbohydrate GalNAc to the side-chain of certain serine and threonine residues in mucin type glycoproteins, are presently unknown. The specificity seems to be modulated by sequence context, secondary structure and surface accessibility. The sequence context of glycosylated threonines was found to differ from that of serine, and the sites were found to cluster. Non-clustered sites had a sequence context different from that of clustered sites. Charged residues were disfavoured at position – 1 and +3. A jury of artificial neural networks was trained to recognize the sequence context and surface accessibility of 299 known and verified mucin type O-glycosylation sites extracted from O-GLYCBASE. The cross-validated NetOglyc network system correctly found 83% of the glycosylated and 90% of the non-glycosylated serine and threonine residues in independent test sets, thus proving more accurate than matrix statistics and vector projection methods. Predictions of O-glycosylation sites in the envelope glycoprotein gp120 from the primate lentiviruses HIV-1, HIV-2 and SIV are presented. The most conserved O-glycosylation signals in these evolutionary-related glycoproteins were found in their first hypervariable loop, V1. However, the strain variation for HIV-1 gp120 was significant. A computer server, available through WWW or E-mail, has been developed for prediction of mucin type O-glycosylation sites in proteins based on the amino acid sequence. The server addresses are http://www.cbs.dtu.dk/services/NetOGlyc/ and netOglyc@cbs.dtu.dk.

mucin type O-glycosylation specificity GalNAc transferase prediction neural networks gp120 SIV HIV 

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References

  1. 1.
    Hounsell E, Davies M, Renouf D (1996) Glycoconj J 13: 19-26.PubMedGoogle Scholar
  2. 2.
    Varki A (1993) Glycobiology 3: 97-130.PubMedGoogle Scholar
  3. 3.
    Jentoft N (1990) Trends in Biochemical Sciences 15: 291-4.PubMedGoogle Scholar
  4. 4.
    Hart GW (1992) Curr Opin Cell Biol 4: 1017-23.PubMedGoogle Scholar
  5. 5.
    Fukuda M (1991) Glycobiology 1: 337-356.PubMedGoogle Scholar
  6. 6.
    Kinloch RA, Sakai Y, Wassarman PM (1995) Proc Natl Acad Sci USA 92: 263-67.PubMedGoogle Scholar
  7. 7.
    Muramatsu T (1993) Glycobiology 3: 294-6.Google Scholar
  8. 8.
    Strous GJ, Dekker J (1992) Crit Rev Biochem Mol Biol 27: 57-92.PubMedGoogle Scholar
  9. 9.
    Carraway K, Hull SR (1991) Glycobiology 1: 131-8.PubMedGoogle Scholar
  10. 10.
    Clausen H, Bennett E (1996) Glycobiology 6: 635-46.PubMedGoogle Scholar
  11. 11.
    Gooley AA, Williams KL (1994) Glycobiology 4: 413-17.PubMedGoogle Scholar
  12. 12.
    Wilson IBH, Gavel Y, Heijne GV (1991) Biochem J 275: 529-34.PubMedGoogle Scholar
  13. 13.
    Wang Y, Abernethy JL, Eckhardt AE, Hill RL (1992) J Biol Chem 267: 12709-16.PubMedGoogle Scholar
  14. 14.
    Hansen JE, Lund O, Engelbrecht J, Bohr H, Nielsen JO, Hansen JES, Brunak S (1995) Biochem J 308: 801-13.PubMedGoogle Scholar
  15. 15.
    O'Connell BC, Hagen FK, Tabak LA (1992) J Biol Chem 267: 25010-18.PubMedGoogle Scholar
  16. 16.
    Wang Y, Agwral N, Eckhard AE, Stevens RD, Hill R (1993) J Biol Chem 268: 22979-83.PubMedGoogle Scholar
  17. 17.
    Nishimori I, Johnson NR, Sanderson SD, Perini F, Mountjoy K, Cerny R, Gros ML, Hollingsworth MA (1994) J Biol Chem 269: 16123-30.PubMedGoogle Scholar
  18. 18.
    O'Connell BC, Tabak LA, Ramasubbu N (1991) Biochem Biophys Res Com 180: 1024-30.PubMedGoogle Scholar
  19. 19.
    Nehrke K, Hagen FK, Tabak LA (1996) J Biol Chem 271: 7061-65.PubMedGoogle Scholar
  20. 20.
    Roth J, Wang Y, Eckhardt AE, Hill RL (1994) Proc Natl Acad Sci USA 91: 8935-9.PubMedGoogle Scholar
  21. 21.
    Asker N, Baeckstrom D, Axelsson MA, Carlstedt I, Hansson GC (1995) Biochem J 308: 873-80.PubMedGoogle Scholar
  22. 22.
    Hansen JE, Lund O, Rapacki K, Clausen H, Mosekilde E, Nielsen JO, Hansen JES (1994) In Protein Structure by Distance Analysis (Bohr H. and Brunak S eds), pp 247-54. Amsterdam: IOS Press.Google Scholar
  23. 23.
    Dahms NM, Hart GW (1986) J Biol Chem 261: 13186-96.PubMedGoogle Scholar
  24. 24.
    Yamada T, Uyeda A, Takao T, Shimonishi Y, Matsushima M, Kikuchi M (1995) Eur J Biochem 230: 965-70.PubMedGoogle Scholar
  25. 25.
    Elliott S, Bartley T, Delorme E, Derby P, Hunt R, Lorenzini T, Parker V, Rohde M, Stoney K (1994) Biochemistry 33: 11237-45.PubMedGoogle Scholar
  26. 26.
    Hagen FK, Van-Wuyckhuyse B, Tabak LA (1993) J Biol Chem 268: 18960-5.PubMedGoogle Scholar
  27. 27.
    Zara J, Hagen FK, Hagen KGT, Van-Wuyckhuyse BC, Tabak LA (1996) Biochem Biophys Res Commun 228: 38-44.PubMedGoogle Scholar
  28. 28.
    Sorensen T, White T, Wandall HH, Kristensen AK, Roepstorff P, Clausen H (1995) J Biol Chem 270: 24166-73.PubMedGoogle Scholar
  29. 29.
    White T, Bennett EP, Takio K, Sorensen T, Bonding N, Clausen H (1995) J Biol Chem 270: 24156-65.PubMedGoogle Scholar
  30. 30.
    Homa FL, Hollander T, Lehman DJ, Thomsen DR, Elharmmer AP (1993) J Biol Chem 268: 12609-16.PubMedGoogle Scholar
  31. 31.
    Meurer JA, Naylor JM, Baker CA, Thomsen DR, Homa FL, Elhammer AP (1995) J Biochemistry 118: 568-74.Google Scholar
  32. 32.
    Hennet T, Hagen F, Tabak L, Marth J (1995) Proc Natl Acad Sci USA 92: 12070-74.PubMedGoogle Scholar
  33. 33.
    Hagen FK, Gregoire CA, Tabak LA (1995) Glycoconj J 12: 901-9.PubMedGoogle Scholar
  34. 34.
    Yoshida A, Hara T, Ikenaga H, Takeuchi M(1995) Glycoconj J 12: 824-82.PubMedGoogle Scholar
  35. 35.
    Bennett E, Hassan H, Clausen H (1996) J Biol Chem 271: 17006-12.PubMedGoogle Scholar
  36. 36.
    Meurer J, Drong R, Homa F, Slightom J, Elhammer A (1996) Glycobiology 6: 231-41.PubMedGoogle Scholar
  37. 37.
    Hansen JE, Lund O, Rapacki K, Brunak S (1997) Nucleic Acid Research 25: 278-82.Google Scholar
  38. 38.
    Elhammer AP, Poorman RA, Brown E, Maggiora LL, Hoogerheide JG, Kzdy FD (1993) J Biol Chem 268: 10029-38.PubMedGoogle Scholar
  39. 39.
    Chou KC (1995) Protein Sci 4: 1365-83.PubMedGoogle Scholar
  40. 40.
    Chou KC, Zhang CT, Kezdy FJ, Poorman RA (1995) Proteins 21: 118-26.PubMedGoogle Scholar
  41. 41.
    Hansen JE, Nielsen C, Arendrup M, Olofsson S, Mathiesen L, Nielsen JO, Clausen H (1991) J Virol 65: 6461-7.PubMedGoogle Scholar
  42. 42.
    Hansen JE, Clausen H, Hu SL, Nielsen JO, Olofsson S (1992) Arch Virol 126: 11-20.PubMedGoogle Scholar
  43. 43.
    Bernstein HB, Tucker SP, Hunter E, Schutzbach JS, Compans RW (1994) J Virol 68: 463-8.PubMedGoogle Scholar
  44. 44.
    Overbaugh J, Rudensey LM (1992) J Virol 66: 5937-48.PubMedGoogle Scholar
  45. 45.
    Pearson WR (1994) Methods Mol Biol 25: 365-89.PubMedGoogle Scholar
  46. 46.
    Hobohm U, Scharf M, Schneider R, Sander C (1992) Protein Sci 1: 409-17.PubMedGoogle Scholar
  47. 47.
    Connolly ML (1983) Science 221: 709-13.PubMedGoogle Scholar
  48. 48.
    Rose GD, Geselowitz AR, Lesser GJ, Lee RH, Zehfus MH (1985) Science 229: 834-8.PubMedGoogle Scholar
  49. 49.
    Blom N, Hansen JE, Blaas D, Brunak S (1996) Protein Sci 5: 2203-16.PubMedGoogle Scholar
  50. 50.
    Shannon CE (1948) Bell System Tech J 27: 379–23, 623-56.Google Scholar
  51. 51.
    Schneider TD, Stephens RM (1990) Nucleic Acids Res 18: 6097-100.PubMedGoogle Scholar
  52. 52.
    Presnell SR, Cohen FE (1993) Annu Rev Biophys Biomol Struct 22: 283-98.PubMedGoogle Scholar
  53. 53.
    Rost B, Sander C (1994) Proteins 19: 55-72.PubMedGoogle Scholar
  54. 54.
    Bohr H, Bohr J, Brunak S, Cotterill RMC, Lautrup B, Nùrskov L, Olsen O, Hsen SB, Peters B (1988) FEBS Lett 241: 223-8.PubMedGoogle Scholar
  55. 55.
    Qian N, Sejnowski TJ (1988) J Mol Biol 202: 865-84.PubMedGoogle Scholar
  56. 56.
    Holley LH, Karplus M (1989) Proc Natl Acad Sci 86: 152-6.PubMedGoogle Scholar
  57. 57.
    MacGregor MJ, Flores TP, Sternberg MJE (1989) Protein Engineering 2: 521-6.PubMedGoogle Scholar
  58. 58.
    Kneller DG, Cohen FE, Langridge R (1990) J Mol Biol 214: 171-82.PubMedGoogle Scholar
  59. 59.
    Rost B, Sander C (1994) Proteins 20: 216-26.PubMedGoogle Scholar
  60. 60.
    Rose B, Casadio R, Fariselli P, Sander C (1995) Protein Sci 4: 521-33.PubMedGoogle Scholar
  61. 61.
    Korning PG, Hebsgaard S, Tolstrup N, Engelbrecht J, Rouzé P, Brunak S (1996) Nucl Acids Res 24: 3439-52.PubMedGoogle Scholar
  62. 62.
    Brunak S, Engelbrecht J, Knudsen S (1991) J Mol Biol 220: 49-65.PubMedGoogle Scholar
  63. 63.
    Rumelhart DE, Hinton GE, Williams RJ (1986) Nature 323: 533-6.Google Scholar
  64. 64.
    Mathews BW (1975) Biochim Biophys Acta 405: 442-51.PubMedGoogle Scholar
  65. 65.
    Nielsen H, Engelbrecht J, Brunak S, von Heijne G (1997) Protein Eng 10: 1-6.Google Scholar
  66. 66.
    Rost B, Sander C (1993) J Mol Biol 232: 584-99.PubMedGoogle Scholar
  67. 67.
    Rost B, Sander C, Schneider R (1994) Comput Appl Biosci 10: 53-60.PubMedGoogle Scholar
  68. 68.
    Hollosi M, Perczel A, Fasman GD (1990) Biopolymers 29: 1549-64.PubMedGoogle Scholar
  69. 69.
    Wragg S, Hagen FK, Tabak LA (1995) J Biol Chem 270: 16947-54.PubMedGoogle Scholar
  70. 70.
    Brockhausen I, Toki D, Brockhausen J, Peters S, Bielfeldt T, Kleen A, Paulsen H, Meldal M, Hagen F, Tabak LA (1996) Glycoconj J 13: 849-56.PubMedGoogle Scholar
  71. 71.
    Hansen JE, Clausen H, Nielsen C, Teglbjaerg LS, Hansen LL, Nielsen CM, Dabelsteen E, Mathiesen L, Hakomori SI, Nielsen JO (1990) J Virol 64: 2833-40.PubMedGoogle Scholar
  72. 72.
    Chackerian B, Rudensey L, Overbaugh J (1997) J Virol 71: 7719-27.PubMedGoogle Scholar
  73. 73.
    Hansen JES, Jansson B, Gram GJ, Clausen H, Nielsen JO, Olofsson S (1996) Arch Virol 141: 291-300.PubMedGoogle Scholar
  74. 74.
    O'Connell B, Tabak L (1993) J Dent Res 72: 1554-8.PubMedGoogle Scholar
  75. 75.
    Geyer R, Dabrowski J, Dabrowski U, Linder D, Schlueter M, Schott HH, Stirm S (1990) Eur J Biochem 187: 95-110.PubMedGoogle Scholar
  76. 76.
    Barker WC, George DG, Mewes HW, Pfeiffer F, Tsugita A (1993) Nucleic Acids Res 21: 3089-96.PubMedGoogle Scholar
  77. 77.
    Bairoch A, Apweiler R (1996) Nucleic Acids Res 24: 21-5.PubMedGoogle Scholar
  78. 78.
    Dahr W, Beyreuther K (1985) Biol Chem Hoppe-Seyler 366: 1067-70.PubMedGoogle Scholar
  79. 79.
    Pisano A, Redmond JW, Williams KL, Gooley AA (1993) Glycobiology 3: 429-35.PubMedGoogle Scholar
  80. 80.
    Murayama J, Yamashita T, Tomita M, Hamada A (1983) Biochim Biophys Acta 742: 477-83.PubMedGoogle Scholar
  81. 81.
    Murayama JI, Tomita M, Hamada A (1982) J Membr Biol 64: 205-15.PubMedGoogle Scholar
  82. 82.
    HonmaK, TomitaM, Hamada A (1980) J Biochem 88: 1679-91.PubMedGoogle Scholar
  83. 83.
    Killeen N, Barclay AN, Willis AC, Williams AF (1987) EMBO J 6: 4029-34.PubMedGoogle Scholar
  84. 84.
    Schmid K, Heidiger MA, Brossmer R, Collins JH, Haupt H, Marti T, Offner GD, Schaller J, Takagaki K, Walsh MT, Schwick HG, Rose FS, Remold-O'Donnell E (1992) Proc Natl Acad Sci 89: 663-7.PubMedGoogle Scholar
  85. 85.
    Putnam FW, Liu YSV, Low TLK (1979) J Biol Chem 254: 2865-74.PubMedGoogle Scholar
  86. 86.
    Robinson EA, Appella E (1979) J Biol Chem 254: 11418-30.PubMedGoogle Scholar
  87. 87.
    Takayasu T, Suzuki S, Kametani F, Takahashi N, Shinoda T, Okuyama T, Munekata E (1982) Biochem Biophys Res Commun 105: 1066-71.PubMedGoogle Scholar
  88. 88.
    Kaushansky K, Lopez JA, Brown CB (1992) Biochemistry 31: 1881-6.PubMedGoogle Scholar
  89. 89.
    Takeuchi M, Kobata A (1991) Glycobiology 1: 337-46.PubMedGoogle Scholar
  90. 90.
    Birken S, Agosto G, Amr S, Nisula B, Cole L, Lewis J, Canfield R (1988) Endocrinology 122: 2054-6.PubMedGoogle Scholar
  91. 91.
    Morgan FJ, Birken S, Canfield RE (1975) J Biol Chem 250: 5247-58.PubMedGoogle Scholar
  92. 92.
    Seidah NG, Chretien M (1981) Proc Natl Acad Sci 78: 4236-40.PubMedGoogle Scholar
  93. 93.
    Bennett HP, Seidah NG, Benjannet S, Solomon S, Chretien M (1986) Int J Pept Protein Res 27: 306-13.PubMedGoogle Scholar
  94. 94.
    Fiat AM, Jolles J, Aubert JP, Loucheux-Lefebvre MH, Jolles P (1980) Eur J Biochem 111: 333-9.PubMedGoogle Scholar
  95. 95.
    Yan SB, Wold F (1984) Biochemistry 23: 3759-65.PubMedGoogle Scholar
  96. 96.
    Schaller J, Marti T, Rosselet SJ, Kampfer U, Rickli EE (1987) Fibrinolysis 1: 91-102.Google Scholar
  97. 97.
    Robb RJ, Kutny RM, Panico M, Morris HR, Chowdhry V (1984) Proc Natl Acad Sci 81: 6486-90.PubMedGoogle Scholar
  98. 98.
    Lottspeich F, Kellermann J, Henschen A, Foertsch B, Muller-Esterl W (1985) Eur J Biochem 152: 307-14.PubMedGoogle Scholar
  99. 99.
    Kellermann J, Lottspeich F, Henschen A, Muller-Esterl W (1986) Adv Exp Med Biol 198: 85-9.PubMedGoogle Scholar
  100. 100.
    Hill HD, Schwyzer M, Steinman HM, Hill RL (1977) J Biol Chem 252: 3799-804.PubMedGoogle Scholar
  101. 101.
    Takahashi N, Takahashi Y, Putnam FW (1985) Proc Natl Acad Sci 82: 1906-10.PubMedGoogle Scholar
  102. 102.
    Brewer Jr HB, Shulman R, Herbert P, Ronan R, Wehrly K (1974) J Biol Chem 249: 4975-84.PubMedGoogle Scholar
  103. 103.
    Kellerman J, Lottspeich F, Geiger R, Deutzmann R (1989) Adv Exp Med Biol 247A: 519-25.PubMedGoogle Scholar
  104. 104.
    Walsh KA, Titani K, Takio K, Kumar S, Hayes R, Petra PH (1986) Biochemistry 25: 7584-90.PubMedGoogle Scholar
  105. 105.
    Lopez Otin C, Grubb A, Mendez E (1984) Arch Biochem Biophys 228: 544-54.PubMedGoogle Scholar
  106. 106.
    Hochstrasser K, Schonberger OL, Rossmanith I, Wachter E (1981) Hoppe-Seyler's Z Physiol Chem 372: 1357-62.Google Scholar
  107. 107.
    Young JD, Tsuchiya D, Sandlin DE, Holroyde MJ (1979) Biochemistry 18: 4444-8.PubMedGoogle Scholar
  108. 108.
    Titani K, Takio K, Handa M, Ruggeri ZM (1987) Proc Natl Acad Sci 84: 5610-14.PubMedGoogle Scholar
  109. 109.
    Gejyo F, Chang JL, Burgi W, Zand Schmid K, Offner GD, Troxler R, Van Halbeek H, Dorland L, Gerwig G, Vliegenthart F (1983) J Biol Chem 258: 4966-71.PubMedGoogle Scholar
  110. 110.
    Watzlawick H, Walsh MT, Yoshioka Y, Schmid K, Brossmer R (1992) Biochemistry 31: 12198-203.PubMedGoogle Scholar
  111. 111.
    Perkins SJ, Smith KF, Amatayakuul S, Ashford D, Rademacher TW, Dwek RA, Lachmann PJ, Harrison RA (1990) J Mol Biol 214: 751-63.PubMedGoogle Scholar
  112. 112.
    Bock SC, Skriver K, Nielsen E, Thogersen HC, Wiman B, Donaldson VH, Eddy RL, Marrinan J, Radziejwska E, Huber R (1986) Biochemistry 25: 4292-301.PubMedGoogle Scholar
  113. 113.
    De Caro AM, Adrich Z, Fournet B, Capon C, Bonicel JJ, De Caro JD, Rovery M(1989) Biochim Biophys Acta 994: 281-84.PubMedGoogle Scholar
  114. 114.
    Wernette-Hammond ME, Lauer S, Corsini A, Walker D, Taylor J, Rall SC (1989) J Biol Chem 264: 9094-101.PubMedGoogle Scholar
  115. 115.
    Hayes GR, Enns CA, Lucas JJ (1992) Glycobiology 2: 355-9.PubMedGoogle Scholar
  116. 116.
    Do SI, Cummings RD (1992) Glycobiology 2: 345-53.PubMedGoogle Scholar
  117. 117.
    Adolf GR, Kalsner I, Ahorn H, Maurer Fogy I, Cantell K (1991) Biochem J 276: 511-18.PubMedGoogle Scholar
  118. 118.
    Voigt CG, Maurer-Fogy I, Adolf GR (1992) FEBS Lett 314: 85-8.PubMedGoogle Scholar
  119. 119.
    Fujiwara S, Shinkai H, Mann K, Timpl R (1993) Matrix 13: 215-22.PubMedGoogle Scholar
  120. 120.
    Clogston CL, Hu S, Boone TC, Lu HS (1993) J Chromatogr 637: 55-62.PubMedGoogle Scholar
  121. 121.
    Minamitake Y, Kodama S, Katayama T, Ada H, Tanaka S, Tsujtmoto M (1990) J Biochem 107: 292-7.PubMedGoogle Scholar
  122. 122.
    Daughaday WH, Trivedi B, Baxter RC (1993) Proc Natl Acad Sci 90: 5823-7.PubMedGoogle Scholar
  123. 123.
    Peters B, Krzesicki R, Perini F, Ruddon R (1989) Endocrinology 124: 1602-12.PubMedGoogle Scholar
  124. 124.
    Pisano A, Jardine DR, Packer NH, Farnsworth V, Carson W, Cartier P, Redmond JW, Williams KL, Gooley AA, (1996) In Techniques in Glycobiology (Townsend R and Hotchkiss A eds). New York: Marcel Dekker Inc.Google Scholar
  125. 125.
    Gooley AA, Classon BJ, Marshcalek R, Williams KL (1991) Biochem Biophys Res Com 178: 1194-1200.PubMedGoogle Scholar
  126. 126.
    Carlsson SR, Lycksell PO, Fukuda M (1993) Arch Biochem Biophys 304: 65-73.PubMedGoogle Scholar
  127. 127.
    Calvete JJ, Muniz-Diaz E (1993) FEBS Lett 328: 30-4.PubMedGoogle Scholar
  128. 128.
    Murayama JI, Utsumi H, Hamada A (1989) Biochim Biophys Acta 999: 273-80.PubMedGoogle Scholar
  129. 129.
    Pisano A, Packer NH, Redmond JW, Williams KL, Gooley AA (1994) Glycobiology 4: 837-44.PubMedGoogle Scholar
  130. 130.
    Shimizu N, Hara H, Sogabe T, Sakai H, Ihara I, Inoue H, Nakamura T, Shimizu S (1992) Biochem Biophys Res Commun 189: 1329-35.PubMedGoogle Scholar
  131. 131.
    Schindler PA, Settineri CA, Collet X, Fielding CJ, Burlingame AL (1995) Protein Sci 4: 791-803.PubMedGoogle Scholar
  132. 132.
    Stadie TR, Chai W, Lawson AM, ByÞeld PG, Hanisch FG (1995) Eur J Biochem 229: 140-7.PubMedGoogle Scholar
  133. 133.
    Wang CS, Dashti A, Jackson KW, Yeh JC, Cummings RD, Tang J (1995) Biochemistry 34: 10639-44.PubMedGoogle Scholar
  134. 134.
    Inoue K, Morita T (1993) Eur J Biochem 218: 153-63.PubMedGoogle Scholar
  135. 135.
    Mizuochi T, Yamashita K, Fujikawa K, Titani K, Kobata A (1980) J Biol Chem 255: 3526-31.PubMedGoogle Scholar

Copyright information

© Kluwer Academic Publishers 1998

Authors and Affiliations

  • Jan E Hansen
    • 1
  • Ole Lund
    • 1
  • Niels Tolstrup
    • 1
  • Andrew A Gooley
    • 2
  • Keith L Williams
    • 2
  • Søren Brunak
    • 1
  1. 1.Center for Biological Sequence AnalysisThe Technical University of DenmarkLyngbyDenmark
  2. 2.School of Biological SciencesMacquarie University SydneyAustralia

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