Module Organization in Proteins and Exon Shuffling



Molecular mechanisms leading to drastic evolutionary change is essentially a recombination of genetic information. Exon shuffling, is one such mechanism used in the creation of novel proteins. The remnants of the shuffling are observed in the split gene structures of eukaryotic cells. Since it was found that the introns in the genes of the globin family corresponded to module joints of the globin chains, such correspondence has been widely observed in various genes. Modules are defined as compact conformational units in the three-dimensional structures of globular proteins. This article focuses on the close correlation between intron positions and module boundaries in several genes and their products. The intron-module relationship shows that exon shuffling is module shuffling in protein language. However, no introns are found at some module joints. It is suggested that many introns were lost during evolution. Though most of the eukaryotic genes are split by introns, introns are located in only a few exceptional genes in the case of prokaryotes. Module organization in proteins is observed also in prokaryotes as well as in eukaryotes. It is highly possible that prokaryotic genes were split by introns and these introns were lost after prokaryote-eukaryote divergence. Imperfect conservation of introns in eukaryotes shows that the module organization, conserved in the three-dimensional structures of contemporary proteins, gives us useful information concerning the evolutionary history of exon shuffling


Module Organization Globin Gene Globular Domain Module Boundary Triosephosphate Isomerase 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 1.
    Gilbert W (1978) Why genes in pieces? Nature 271: 501–501PubMedCrossRefGoogle Scholar
  2. 2.
    Doolittle WF (1978) Genes in pieces: Were they ever together? Nature 272: 581–582CrossRefGoogle Scholar
  3. 3.
    Darnell JE Jr (1978) Implications of RNA* RNA splicing in evolution of eukaryotic cells. Science 202: 1257–1260PubMedCrossRefGoogle Scholar
  4. 4.
    Blake CCC (1978) Do genes-in-pieces imply proteins-in-pieces? Nature 273: 267–267CrossRefGoogle Scholar
  5. 5.
    Crick F (1979) Split genes and RNA splicing. Science 204: 264–271PubMedCrossRefGoogle Scholar
  6. 6.
    Mount SM (1982) A catalogue of splice junction sequences. Nucleic Acid Res 10: 459–472PubMedCrossRefGoogle Scholar
  7. 7.
    Perler F, Efstratiadis A, Lomedico P, Gilbert W, Kolodner R, Dodgson J (1980) The evolution of genes: The chicken preproinsulin gene. Cell 20: 555–566PubMedCrossRefGoogle Scholar
  8. 8.
    Stein JP, Carterall JF, Kristo P, Means AR, O’Malley BW (1980) Ovomucoid intervening sequences specify functional domains and generate protein polymorphism. Cell 21: 681–687PubMedCrossRefGoogle Scholar
  9. 9.
    Eiferrman FA, Young PR, Scott RW, Tilghman SM (1981) Intragenic amplification and divergence in the mouse a-fetoprotein gene. Nature 294: 713–718CrossRefGoogle Scholar
  10. 10.
    Tonegawa S, Maxam AM, Tizard R, Bernard O, Gilbert W (1978) Sequence of a mouse germ-line gene for a variable region of an immunoglobulin light chain. Proc Natl Acad Sci USA 75: 1485–1489PubMedCrossRefGoogle Scholar
  11. 11.
    Gō M (1981) Correlation of DNA exonic regions with protein structural units in haemoglobin. Nature 291: 90–92PubMedCrossRefGoogle Scholar
  12. 12.
    Richardson J (1981) The anatomy and taxonomy of protein structure. Adv Protein Chem 34: 167–339PubMedCrossRefGoogle Scholar
  13. 13.
    Gō M (1983) Modular structural units, exons, and function in chicken lysozyme. Proc Natl Acad Sci USA 80: 1964–1968PubMedCrossRefGoogle Scholar
  14. 14.
    Gō M (1985) Protein structures and split genes. Adv Biophys 19: 91–131PubMedCrossRefGoogle Scholar
  15. 15.
    Leder A, Miller HI, Hamer DH, Seidman JG, Norman B, Sullivan M, Leder P (1978) Comparison of cloned mouse α- and ß-globin genes: Conservation of intervening sequence location and extragenic homology. Proc Natl Acad Sci USA. 74: 6187–6191CrossRefGoogle Scholar
  16. 16.
    Perutz MF, Muirhead H, Cox JM, Goaman LCG (1968) Three-dimensional Fourier synthesis of horse oxyhaemoglobin at 2.8Å resolution: The atomic model. Nature 219: 131–139PubMedCrossRefGoogle Scholar
  17. 17.
    Jensen EØ, Paludan K, Hyldig-Niellsen JJ, Jørgensen P, Marcker KA (1981) The structure of chromosomal leghaemoglobin gene from soybean. Nature 291: 677–679CrossRefGoogle Scholar
  18. 18.
    Blanchetot A, Wilson V, Wood D, Jeffreys AJ (1983) The seal myoglobin gene: An unusually long globin gene. Nature 301: 732–734PubMedCrossRefGoogle Scholar
  19. 19.
    Antoine M, Niessing J (1984) Intron-less globin genes in the insect Chironomus thummi thummi. Nature 310: 795–798CrossRefGoogle Scholar
  20. 20.
    Jhiang SM, Garey JR, Riggs AF (1988) Exon-intron organization in genes of earthworm and vertebrate globins. Science 240: 334–336PubMedCrossRefGoogle Scholar
  21. 21.
    Landsmann J, Dennis ES, Higgins TJV, Appleby CA, Kortt AA, Peacock WJ (1986) Common evolutionary origin of legume and nonlegume plant haemoglobin. Nature 324: 166–168CrossRefGoogle Scholar
  22. 22.
    Bogusz D, Appleby CA, Landsmann J, Dennis ES, Trinick MJ, Peacock WJ (1988) Functional haemoglobin genes in non-nodulating plants. Nature 331: 178–180PubMedCrossRefGoogle Scholar
  23. 23.
    Dayhoff MO, Hunt LT, McLaughlin PJ, Jones DD (1972) Gene duplications in evolution: The globins. In: Dayhoff M (ed) Atlas of protein sequence and structure. Natl Biomed Found Washington DC, vol 5, pp 17–30Google Scholar
  24. 24.
    Wakabayashi S, Matsubara H, Webster DA (1986) Primary sequence of a dimeric bacterial haemoglobin from Vitreoscilla. Nature 322: 481–483PubMedCrossRefGoogle Scholar
  25. 25.
    Jung A, Sippel AE, Greg M, Schütz G (1980) Exons encode functional and structural units of chicken lysozyme. Proc Natl Acad Sci USA 77: 5759–5763PubMedCrossRefGoogle Scholar
  26. 26.
    Qasba PK, Safaya SK (1984) Similarity of the nucleotide sequences of rat α- lactalubumin and chicken lysozyme genes. Nature 308: 377–380PubMedCrossRefGoogle Scholar
  27. 27.
    Gō M, Nosaka M (1987) Protein architecture and the origin of introns. Cold Spring Harbor Symp Quant Biol 52: 915–924PubMedGoogle Scholar
  28. 28.
    Banner DW, Bloomer AC, Petsko GA, Phillips DC, Pogson CI, Wilson IA, Corran PH, Furth AJ, Milman JD, Offord RE, Priddle JD, Waley SG (1975) Structure of chicken muscle triose phosphate isomerase determined crystallographically at 2.5Å resolution using amino acid sequence data. Nature 255: 609–614PubMedCrossRefGoogle Scholar
  29. 29.
    Zaug AJ, Been MD, Cech TR (1986) The Tetrahymena ribozyme acts like an RNA restriction endonuclease. Nature 324: 429–433PubMedCrossRefGoogle Scholar
  30. 30.
    Guerrier-Takada C, Lumelsky N, Altman S (1989) Specific interactions in RNA enzyme-substrate complexes. Science 246: 1578–1584PubMedCrossRefGoogle Scholar
  31. 31.
    Yanagawa H, Kojima K, Ito M, Handa N (1990) Synthesis of poly-peptides by microwave heating I. Formation of polypeptides during repeated hydration-dehydration cycles and their characterization. J Mol Evol 31: 180–186PubMedCrossRefGoogle Scholar
  32. 32.
    Acevedo OL, Orgel LE (1986) Template-directed oligonucleotide ligation on hydroxylapatite. Nature 321: 790–792PubMedCrossRefGoogle Scholar
  33. 33.
    Blake CCC (1981) Exons and the structure, function, and evolution of haemoglobin. Nature 291: 616–616PubMedCrossRefGoogle Scholar
  34. 34.
    Levin R (1982) On the origin of introns. Science 217:921–922CrossRefGoogle Scholar
  35. 35.
    Straus D, Gilbert W (1985) Genetic engineering in the Precambrian: Structure of chicken triosephosphate isomerase gene. Mol Cell Biol 5: 3497–3506PubMedGoogle Scholar
  36. 36.
    Marchionni M, Gilbert W (1986) The triosephosphate isomerase gene from maize: Introns antedate the plant-animal divergence. Cell 46: 133–141PubMedCrossRefGoogle Scholar
  37. 37.
    McKnight GL, O’Hara PJ, Parker ML (1986) Nucleotide sequence of the triosephosphate isomerase gene from Aspergillusnidulans: Implications for a differential loss of introns. Cell 46: 143–147PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag Tokyo 1991

Authors and Affiliations

  1. 1.Department of Biology, Faculty of ScienceNagoya UniversityFuro-cho, Chikusa-ku, NagoyaJapan

Personalised recommendations