Journal of Molecular Evolution

, Volume 12, Issue 3, pp 219–236

Two types of amino acid substitutions in protein evolution


  • Takashi Miyata
    • Department of BiologyKyushu University
  • Sanzo Miyazawa
    • Department of BiologyKyushu University
  • Teruo Yasunaga
    • Department of BiologyKyushu University

DOI: 10.1007/BF01732340

Cite this article as:
Miyata, T., Miyazawa, S. & Yasunaga, T. J Mol Evol (1979) 12: 219. doi:10.1007/BF01732340


The frequency of amino acid substitutions, relative to the frequency expected by chance, decreases linearly with the increase in physico-chemical differences between amino acid pairs involved in a substitution. This correlation does not apply to abnormal human hemoglobins. Since abnormal hemoglobins mostly reflect the process of mutation rather than selection, the correlation manifest during protein evolution between substitution frequency and physico-chemical difference in amino acids can be attributed to natural selection. Outside of ‘abnormal’ proteins, the correlation also does not apply to certain regions of proteins characterized by rapid rates of substitution. In these cases again, except for the largest physico-chemical differences between amino acid pairs, the substitution frequencies seem to be independent of the physico-chemical parameters. The limination of the substituents involving the largest physicochemical differences can once more be attributed to natural selection. For smaller physico-chemical differences, natural selection, if it is operating in the polypeptide regions, must be based on parameters other than those examined.

Key words

Amino acid substitutionPhysico-chemical differenceConservativeLow-constraintProtein evolution

Copyright information

© Springer-Verlag 1979