Journal of Molecular Evolution

, Volume 7, Issue 1, pp 1–57 | Cite as

The appearance of new structures and functions in proteins during evolution

  • Emile Zuckerkandl


The likelihood of a de novo generation of classes of efficient proteins through neoformation of DNA, through modification of expressed DNA, and through modification of nonexpressed DNA is examined. So is the likelihood that newly formed inefficient enzymes be turned into efficient enzymes. The conclusions are that neither gene duplicates nor dormant genes represent promising materials for a de novo generation of protein classes, that (with exceptions) such generation is unlikely to have taken place in recent evolution, that new structural genes must nearly consistently derive from preexisting structural genes, and that new functions can be evolved only on the basis of old proteins. Conditions of protein evolution in prokaryotes suggest that the saltatory formation of protein classes is as unlikely in prokaryotes as in eukaryotes. Data on the history of a few protein classes are reviewed to illustrate the preceding inferences. The analysis leads to the hypothesis that most protein classes originated before the major elements of the translation apparatus of modern cells were fully evolved. If simple sequence DNA is turned into structural genes by evolution, this process (again with exceptions) is considered to have taken place only at that very remote period. A polyphyletic origin of proteins is thought to date back to the same era. It is proposed that the development of genic multiplicity and of marked structural and functional diversity of proteins may have come about in the earliest cells primarily through the independent generation of structurally different polymerases in different protocells, followed by cell conjugation and the subsequent use by enriched cells of supernumerary types of polymerase for evolving further functions. Functional growth, as it took place at early times, is briefly discussed as well as functional change. The foundations for new functional developments in old proteins are analyzed. In considering the evolutionary recovery of lost functions, aspects of cell differentiation and gene regulation are linked with the evolutionary picture. The distinction between eurygenic and stenogenic control of gene activity is used. Next to gene deletion, cell and tissue deletion is held to be an event of general evolutionary significance, through cell and tissue origination that presumably accompanies the restoration of a lost molecular function.

Key words

Protein Evolution Protein Classes Protein Function Biogenesis Cell Differentiation Gene Control 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. Appleby, C.A. (1969). Biochim.Biophys.Acta 172, 88Google Scholar
  2. August, J.T., Eoyang, L., Franze de Fernandez, M.T., Hayward, W.S., Kuo, C.H., Silverman, P.M. (1972). In: International Symposium on Protein Synthesis and Nucleic Acids, Proc.XI Latin Am.Symp., La Plata 1971. New York: Plenus PressGoogle Scholar
  3. Barker, W.C., McLaughlin, P.J., Dayhoff, M.O. (1972). Evolution of a complex system. In: Atlas of protein sequence and structure, Vol. 5, M.O. Dayhoff, ed., p. 31. Washington, D.C.: National Biomedical Research FoundationGoogle Scholar
  4. Barnard, E.A., Cohen, M.S., Gold, M.H., Kim, J.-K. (1972). Nature 240, 395Google Scholar
  5. Bendich, A.J., McCarthy, B.J. (1970). Proc.Natl.Acad.Sci. 65, 349Google Scholar
  6. Benvenista, R., Davies, J. (1973). Ann.Rev.Biochem. 42, 471Google Scholar
  7. Birnstiel, M.L., Weinberg, E.S., Pardue, M.L. (1973). In: Molecular cytogenetics, B.A. Hamkalo, J. Papaconstantinou, eds., p. 75. New York: Plenum PressGoogle Scholar
  8. Bishop, J.O., Freeman, K.B. (1973). Cold Spring Harbor Symp.Quant.Biol. 38, 707Google Scholar
  9. Bishop, J.O., Morton, J.C., Rosbash, M., Richardson, M. (1974). Nature 250, 199Google Scholar
  10. Britten, R.J., Davidson, E.H. (1969). Science 165, 349Google Scholar
  11. Britten, R.J., Kohne, D.E. (1968). Science 161, 529Google Scholar
  12. Broda, E. (1971). Bioenergetic evolution. In: Biochemical evolution and the origin of life, E. Schoffeniels, ed., p. 224. Amsterdam: North HollandGoogle Scholar
  13. Brown, A.K., Wilmore, P.J. (1974). Chromosoma 47, 379Google Scholar
  14. Campbell, J.H., Lengyel, J.A., Langridge, J. (1973). Proc.Natl.Acad.Sci. 70, 1841Google Scholar
  15. Cantor, C.R., Jukes, T.H. (1966). Proc.Natl.Acad.Sci. 56, 177Google Scholar
  16. Capon, B. (1964). Quart.Revs. 18, 45Google Scholar
  17. Cavadore, J.C. (1971). Polycondensation d'α-amino acides en milieu aqueux. Thèse doctorat ès sciences physiques, Université des Sciences et Techniques du Languedoc, MontpellierGoogle Scholar
  18. Cavadore, J.C., Previero, A. (1969). Bull.Soc.Chim.Biol. 51, 1245Google Scholar
  19. Coletti-Previero, M.A., Previero, A., Zuckerkandl, E. (1969). J.Mol.Biol. 39, 493Google Scholar
  20. Colman, P.M., Jansonius, J.N., Matthews, B.W. (1972). J.Mol.Biol. 70, 701Google Scholar
  21. Corbin, K.W., Uzzell, T. (1970). Am.Nat. 104, 37Google Scholar
  22. Davidson, E.H., Britten, R.J. (1973). Quart.Revs.Biol. 48, 565Google Scholar
  23. Davidson, E.H., Hough, B.R. (1971). J.Mol.Biol. 56, 491Google Scholar
  24. Dayhoff, M.O. (1972). Atlas of protein sequence and structure, Vol. 5. Washington, D.C.: National Biomedical Research FoundationGoogle Scholar
  25. Dayhoff, M.O. (1974). Fed.Proc. 33, 2314Google Scholar
  26. Dickerson, R.E. (1971). J.Mol.Biol. 57, 1Google Scholar
  27. Eck, R.V., Dayhoff, M.O. (1966). Science 152, 363Google Scholar
  28. Epstein, C.J. (1964). Nature 203, 1350Google Scholar
  29. Farquhar, M.N., McCarthy, B.J. (1973). Biochem. 12, 4113Google Scholar
  30. Faye, G., Fukuhara, H., Grandchamp, C., Lazowska, J., Michel, F., Casey, J., Getz, G.S., Locker, J., Rabinowitz, M., Balotin-Fukuhara, M., Coen, D., Deutsch, J., Dujou, B., Netter, P., Slonimski, P.P. (1973). Biochim. 55, 779Google Scholar
  31. Fitch, W.M. (1970a). System.Zool. 19, 99Google Scholar
  32. Fitch, W.M. (1970b). J.Mol.Biol. 49, 15Google Scholar
  33. Fox, S.W. (1973). Naturwiss. 60, 359Google Scholar
  34. Fox, S.W., McCauley, R.J., Wood, A. (1967). Comp.Biochem.Physiol. 20, 773Google Scholar
  35. Galau, G.A., Britten, R.J., Davidson, E.H. (1974). Cell 2, 9Google Scholar
  36. Gall, J.G., Cohen, E.H., Polan, M.L. (1971). Chromosoma 33, 319Google Scholar
  37. Gatlin, L.L. (1974). J.Mol.Evol. 3, 189Google Scholar
  38. Goodman, M. (1961). Human Biol. 33, 131Google Scholar
  39. Goodman, M. (1964). The specificity of proteins and the process of primate evolution. In: Protides of the biological fluids, H. Peeters, ed., p.70. Amsterdam: ElsevierGoogle Scholar
  40. Goldberg, R.B., Galau, G.A., Britten, R.J., Davidson, E.H. (1973). Proc.Natl.Acad.Sci. 70, 3516Google Scholar
  41. Goldfine, H. (1972). Advan.Microbiol.Physiol. 8, 1Google Scholar
  42. Greenberg, J.R., Perry, R.P. (1971). J.Cell Biol. 50, 774Google Scholar
  43. Grey, H.M. (1971). Phylogeny of immunoglobulins. In: Biochemical evolution and the origin of life, E. Schoffeniels, ed., p.96. Amsterdam: North HollandGoogle Scholar
  44. Grigliatti, T.A., White, B.N., Tener, G.M., Kaufman, T.C., Holden, J.J., Suzuki, D.T. (1973). Cold Spring Harbor Symp.Quant.Biol. 38, 461Google Scholar
  45. Hartley, B.S., Burleigh, B.D., Midwinter, C.G., Moore, C.H., Morris, H.R., Rigby, P.W.J., Smith, M.J., Taylor, S.S. (1972). Proc.FEBS Meetings 29, 151Google Scholar
  46. Hennig, W., Hennig, I., Stein, H. (1970). Chromosoma 32, 31Google Scholar
  47. Horowitz, N.H. (1965). The evolution of biochemical syntheses -retrospect and prospect. In: Evolving genes and proteins, V. Bryson, H.J. Vogel, eds., p. 15. New York: Academic PressGoogle Scholar
  48. Ingram, V.M. (1961). Nature 189, 704Google Scholar
  49. Jeuniaux, Ch. (1971). On some biochemical aspects of regressive evolution in animals. In: Biochemical evolution and the origin of life, E.Schoffeniels, ed., p. 304. Amsterdam: North HollandGoogle Scholar
  50. Kedes, L., Birnstiel, M.L. (1971). Nature New Biol. 230, 165Google Scholar
  51. Kimura, M. (1968). Genet.Res. 11, 247Google Scholar
  52. King, J.L. (1972). The role of mutation in evolution. In: Proceedings of the Sixth Berkeley Symposium on Mathematical Statistics and Probability, Vol. 5, p. 69. Berkeley: University of California PressGoogle Scholar
  53. King, J.L., Jukes, T.H. (1969). Science 164, 788Google Scholar
  54. Klippenstein, G.L. (1972). Biochem. 11, 372Google Scholar
  55. Koch, H.J.A., Bergström, E., Evans, J.C. (1964). Mededel.Koninkl. Vlaamse Acad.Wetenschap.Belg. 26, 1Google Scholar
  56. Koch, A.I. (1972). Genetics 72, 297Google Scholar
  57. Kohne, D.E. (1970). Quart.Revs.Biophys. 3, 327Google Scholar
  58. Laird, C.D., McConaughy, B.L., McCarthy, B.J. (1969). Nature 224, 149Google Scholar
  59. Lee, C.C., Thomas, C.A.,Jr. (1973). J.Mol.Biol. 77, 25Google Scholar
  60. Lewis, E.B. (1951). Cold Spring Harbor Symp.Quant.Biol. 16, 159Google Scholar
  61. Lucas, F., Rudall, K.M. (1968). In: Comprehensive biochemistry, M. Florkin, E.H. Stotz, eds., Vol. 26, part B, p. 475. Amsterdam: ElsevierGoogle Scholar
  62. Lwoff, A. (1943). L'Evolution physiologique. Etude des pertes de fonctions chez les microorganismes. Paris: HermannGoogle Scholar
  63. Maden, B.E.H. (1971). Progr.Biophys.Mol.Biol. 22, 129Google Scholar
  64. Manwell, C., Baker, C.M.A. (1970). Molecular biology and the origin of species. London: Sidgwick and JacksonGoogle Scholar
  65. Margoliash, E., Fitch, W.M. (1970). Miami Winter Symp. 1, 33. Amsterdam: North HollandGoogle Scholar
  66. Margulis, L. (1970). Origin of eukaryotic cells. New Haven: Yale University PressGoogle Scholar
  67. Markland, F.S., Smith, E.L. (1967). J.Biol.Chem. 242, 5198Google Scholar
  68. Martin, F. (1974). Etude de l'hémoglobine d'un Sélacien,Scylliorhinus canicula. Thèse de doctorat ès-sciences physiques, Université des Sciences et Techniques du Languedoc, MontpellierGoogle Scholar
  69. Matsubara, H., Jukes, T.H., Cantor, C.R. (1969). Brookhaven Symp.Biol. 21, 201Google Scholar
  70. McCarthy, B.J., Nishiura, J.T., Doenecke, D., Nasser, D.S., Johnson, C.B. (1973). Cold Spring Harbor Symp.Quant.Biol. 38, 763Google Scholar
  71. McLachlan, A.D., Shotton, D.M. (1971). Nature New Biol. 229, 202Google Scholar
  72. McLaughlin, P.J., Dayhoff, M.O. (1973). J.Mol.Evol. 2, 99Google Scholar
  73. Medvedev, Z.A. (1972). J.Mol.Evol. 1, 270Google Scholar
  74. Metz, C.W. (1947). Am.Nat. 81, 81Google Scholar
  75. Miller, O.L., Hamkalo, B.A. (1972).Google Scholar
  76. Monod, J. (1971). Chance and necessity. New York: KnopfGoogle Scholar
  77. Neurath, H., Bradshaw, R.A., Arnon, R. (1970). Homology and phylogeny of proteolytic enzymes. In: Structure-function relationships of proteolytic enzymes, P. Desnuelle, H. Neurath, M. Ottesen, eds., p. 113. Copenhagen: MunksgaardGoogle Scholar
  78. Ohno, S. (1970). Evolution by gene duplication. Berlin, Heidelberg, New York: SpringerGoogle Scholar
  79. Ohta, T., Kimura, M. (1971). Nature 233, 118Google Scholar
  80. Pauling, L., Zuckerkandl, E. (1963). Acta Chem.Scand. 17, S9Google Scholar
  81. Pauling, L., Zuckerkandl, E. (1972). Chance in evolution - some philosophical remarks. In: Molecular evolution, D.L. Rohlfing, A.I. Oparin, eds., p. 113. New York: PlenumGoogle Scholar
  82. Perutz, M.F., Kendrew, J.C., Watson, H.C. (1965). J.Mol.Biol. 13, 669Google Scholar
  83. Plagens, U. (1971). Vergleichende Untersuchungen der Hämoglobine verschiedener Chironomiden. Inaugural-Dissertation, Ludwig-Maximilians Universität, MunichGoogle Scholar
  84. Prokofyeva-Belgovskaya, A.A. (1947). J.Genet. 48, 80Google Scholar
  85. Prosser, C.Ladd (1973). Comparative animal physiology, 3rd edition. Philadelphia: W.B. SaundersGoogle Scholar
  86. Quincey, R.V. (1971). Biochem.J. 123, 227Google Scholar
  87. Rae, P.M.M. (1972). Advan.Cell Mol.Biol. 2, 109Google Scholar
  88. Rice, N.R. (1972). Change in repeated DNA in evolution. In: Evolution of genetic systems, H.H. Smith, ed., p. 44. New York: Gordon and BreachGoogle Scholar
  89. Ris, H., Kubai, D.F. (1970). Ann.Rev.Genet. 4, 263Google Scholar
  90. Robertus, J.D., Alden, R.A., Birktoft, J.J., Kraut, J., Powers, J.C., Wilcox, P.E. (1972). Biochem. 11, 3439Google Scholar
  91. Rohlfing, D.L., Fox, S.W. (1967). Arch.Biochem.Biophys. 118, 122Google Scholar
  92. Rohlfing, D.L. (1969). Advan.Catalysis 20, 373Google Scholar
  93. Rossmann, M.G., Moras, D., Olsen, K.W. (1974). Nature 250, 194Google Scholar
  94. Russel, R.L., Abelson, J.N., Landy, A., Gefter, M.L., Brenner, S., Smith, J.D. (1970). J.Mol.Biol. 47, 1Google Scholar
  95. Ruud, J.T. (1954). Nature 173, 848Google Scholar
  96. Sallei, J.P., Zuckerkandl, E. (1975). Biochim. 57, 343Google Scholar
  97. Schachman, H.K., Adler, J., Radding, C.M., Lehmann, I.R., Kornberg, A. (1960). J.Biol.Chem. 235, 3242Google Scholar
  98. Schroeder, W.A., Huisman, T.H.J. (1970). Investigations of molecular variation in human fetal hemoglobin in the infant and in certain hematological conditions in the adult. In: Protides of the biological fluids, H. Peeters, ed., p. 249. Oxford: PergamonGoogle Scholar
  99. Schulz, G.E., Schirmer, R.H. (1974). Nature 250, 144Google Scholar
  100. Simoni, R.D., Criddle, R.S., Stumpf, D.K. (1967). J.Biol.Chem. 242, 573Google Scholar
  101. Slizynski, B.M. (1945). Proc.Roy.Soc.Edinburgh B, 62, 114Google Scholar
  102. Smith, E.L., De Lange, R.J., Bonner, J. (1970). Physiol.Rev. 50, 159Google Scholar
  103. Spradling, A., Penman, S., Campo, M.S., Bishop, J.O. (1974). Cell 3, 23Google Scholar
  104. Stebbins, G. Ledyard (1971). Processes of organic evolution, 2nd ed., Englewood Cliffs, N.J.: Prentice HallGoogle Scholar
  105. Steen, J.B., Berg, T. (1966). Comp.Biochem.Physiol. 18, 517Google Scholar
  106. Stenzel, P. (1974). Nature 252, 62Google Scholar
  107. Suzuki, Y., Gage, L.P., Brown, D.B. (1972). J.Mol.Biol. 70, 637Google Scholar
  108. Thomas, C.A., Jr. (1966). Progr.Nucl.Ac.Res.Mol.Biol. 5, 315Google Scholar
  109. Titani, K., Hermodson, M.A., Ericsson, L.H., Walsh, K.K., Neurath, H. (1972). Nature New Biol. 238, 35Google Scholar
  110. Walker, P.M.B. (1968). Nature 219, 228Google Scholar
  111. Walker, P.M.B. (1971). Progr.Biophys.Mol.Biol. 23, 147Google Scholar
  112. Walker, P.M.B., Flamm, W.G., Mclaren, A. (1969). Highly repetitive DNA in rodents. In: Handbook of molecular cytology, A. Lima de Faria, ed., p. 52. Amsterdam: North HollandGoogle Scholar
  113. Walvig, F. (1958). Nytt Magasin Zool. 6, 111Google Scholar
  114. Watts, D.C. (1971). Evolution of phosphagen kinases. In: Biochemical evolution and the origin of life, E. Schoffeniels, ed., p. 150. Amsterdam: North HollandGoogle Scholar
  115. Welling, G.W., Leijenaar-van den Berg, G., van Dijk, B., van den Berg, A., Groen, G., Gaastra, W., Emmens, M., Beintema, J.J. (1975). BioSystems 6, 239Google Scholar
  116. Woese, C.R. (1965). Proc.Natl.Acad.Sci. 54, 1546Google Scholar
  117. Woese, C.R. (1969). J.Mol.Biol. 43, 235Google Scholar
  118. Woese, C.R. (1971). J.Theoret.Biol. 33, 29Google Scholar
  119. Ycas, M. (1972). J.Mol.Evol. 2, 17Google Scholar
  120. Ycas, M. (1974). J.Theoret.Biol. 44, 145Google Scholar
  121. Yunis, J.J., Yasmineh, W.G. (1971). Science 174, 1200Google Scholar
  122. Zamenhof, S., Eichorn, H.H. (1967). Nature 216, 456Google Scholar
  123. Zubay, G., Watson, M.R. (1959). J.Biophys.Biochem.Cytol. 5, 51Google Scholar
  124. Zuckerkandl, E. (1960). Ann.Inst.Oceanog. 38, 1Google Scholar
  125. Zuckerkandl, E. (1965). Sci.Am. 212, 110Google Scholar
  126. Zuckerkandl, E. (1970). European J.Clin.Biol.Res. 15, 369Google Scholar
  127. Zuckerkandl, E. (1972). Biochim. 54, 1095Google Scholar
  128. Zuckerkandl, E. (1974a). Biochim. 56, 937Google Scholar
  129. Zuckerkandl, E. (1974b). Accomplissements et perspectives de la paleogenetique chimique. In: Ecole de Roscoff - 1974, p. 69. Paris: Centre National de la Recherche ScientifiqueGoogle Scholar
  130. Zuckerkandl, E. (1976a). J.Mol.Evol., in pressGoogle Scholar
  131. Zuckerkandl, E. (1976b). Programs of gene action and progressive evolution. In: Molecular anthropology, M. Goodman, R.E. Tashian, eds. New York: Plenum, in pressGoogle Scholar
  132. Zuckerkandl, E., Derancourt, J., Vogel, H. (1971). J.Mol.Biol. 59, 473Google Scholar
  133. Zuckerkandl, E., Pauling, L. (1962). Molecular disease, evolution, and genic heterogeneity. In: Horizons in biochemistry, M. Kasha, B. Pullman, eds., p. 189. New York: Academic PressGoogle Scholar
  134. Zuckerkandl, E., Pauling, L. (1965a). J.Theoret.Biol. 8, 357Google Scholar
  135. Zuckerkandl, E., Pauling, L. (1965b). Evolutionary divergence and convergence in proteins. In: Evolving genes and proteins., V. Bryson, H.J. Vogel, eds., p. 97. New York: Academic PressGoogle Scholar

Copyright information

© Springer-Verlag 1975

Authors and Affiliations

  • Emile Zuckerkandl
    • 1
  1. 1.Marine Biological LaboratoryWoods HoleUSA

Personalised recommendations