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Proc Natl Acad Sci U S A. Aug 1969; 63(4): 1181–1188.
PMCID: PMC223447



The rate of amino acid substitutions in the evolution of homologous proteins is remarkably constant. Furthermore, estimated rates of amino acid substitutions based on comparisons of the alpha hemoglobin chains of various mammals with that of the carp are about the same as those based on comparisons of the carp alpha and mammalian beta or the alpha and beta chains in mammals. These uniformities are regarded as evidence for the hypothesis that a majority of amino acid substitutions that occurred in these proteins are the result of random fixation of selectively neutral or nearly neutral mutations.

Two implications of this possibility are discussed: (a) Random gene frequency drift is playing an important role in determining the genetic structure of biological populations and (b) genes in “living fossils” may be expected to have undergone as many DNA base (and therefore amino acid) substitutions as corresponding genes (proteins) in more rapidly evolving species.

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Selected References

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  • Ohno S, Wolf U, Atkin NB. Evolution from fish to mammals by gene duplication. Hereditas. 1968;59(1):169–187. [PubMed]
  • Kimura M. Evolutionary rate at the molecular level. Nature. 1968 Feb 17;217(5129):624–626. [PubMed]
  • King JL, Jukes TH. Non-Darwinian evolution. Science. 1969 May 16;164(3881):788–798. [PubMed]
  • Kimura M, Ohta T. The Average Number of Generations until Fixation of a Mutant Gene in a Finite Population. Genetics. 1969 Mar;61(3):763–771. [PMC free article] [PubMed]
  • Kimura M. Genetic variability maintained in a finite population due to mutational production of neutral and nearly neutral isoalleles. Genet Res. 1968 Jun;11(3):247–269. [PubMed]
  • VOGEL F. A PRELIMINARY ESTIMATE OF THE NUMBER OF HUMAN GENES. Nature. 1964 Feb 22;201:847–847. [PubMed]
  • Cox EC, Yanofsky C. Altered base ratios in the DNA of an Escherichia coli mutator strain. Proc Natl Acad Sci U S A. 1967 Nov;58(5):1895–1902. [PMC free article] [PubMed]
  • SUEOKA N. On the genetic basis of variation and heterogeneity of DNA base composition. Proc Natl Acad Sci U S A. 1962 Apr 15;48:582–592. [PMC free article] [PubMed]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences


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