Neutral Evolution



By “neutral evolution” I mean the process of substitutions of selectively neutral (i. e., selectively equivalent) mutants in the species through random genetic drift under continued mutation pressure. According to the neutral theory of molecular evolution, the great majority of evolutionary changes at the molecular level (such as DNA base substitutions and amino acid replacements) are the result of such neutral evolution, rather than the result of Darwinian adaptive evolution. The neutral theory also claims that most of the genetic variability within species at the molecular level (such as protein and DNA polymorphism) is selectively neutral or very nearly neutral so that the majority of polymorphic alleles are maintained in the species by the balance between mutational input and random extinction, but not by balancing natural selection. The neutral theory is based on simple assumptions, and this enables us to develop mathematical theories based on population genetics to treat these phenomena of evolution and variation in quantitative terms. This permits the theory to be tested against actual observations. In this paper, I review some recent data strongly suggesting neutral evolution, including such topics as pseudoglobin genes of the mouse, αA-crystallin genes of the blind mole rat and genes of RNA viruses. I also discuss some problems of DNA polymorphism in the light of the neutral theory. Finally, I emphasize the importance of population genetics in understanding the mechanisms of molecular evolution. It is concluded that, since the origin of life on Earth, the great majority of evolutionary changes have been neutral rather than Darwinian.


Molecular Evolution Neutral Theory Nucleotide Site Neutral Evolution Average Heterozygosity 
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  1. 1.
    Kimura M (1968) Evolutionary rate at the molecular level. Nature 217: 624–626PubMedCrossRefGoogle Scholar
  2. 2.
    Kimura M (1983) The neutral theory of molecular evolution. Cambridge University Press, CambridgeGoogle Scholar
  3. 3.
    Kimura M, Crow JF (1964) The number of alleles that can be maintained in a finite population. Genetics 49: 725–738PubMedGoogle Scholar
  4. 4.
    Kimura M (1968) Genetic variability maintained in a finite population due to mutational production of neutral and nearly neutral alleles. Genet Res 11: 247–269PubMedCrossRefGoogle Scholar
  5. 5.
    Kimura M (1969) The number of heterozygous nucleotide sites maintained in a finite population due to steady flux of mutations. Genetics 61: 893–903PubMedGoogle Scholar
  6. 6.
    Kimura M (1971) Theoretical foundation of population genetics at the molecular level. Theor Popul Biol 2: 174–208PubMedCrossRefGoogle Scholar
  7. 7.
    Nei M (1987) Molecular evolutionary genetics. Columbia University Press, New YorkGoogle Scholar
  8. 8.
    Ohta T, Aoki K (eds) (1985) Population genetics and molecular evolution. Japan Scientific Societies, Tokyo and Springer, BerlinGoogle Scholar
  9. 9.
    Takahata N, Crow JF (eds) (1990) Population biology of genes and molecules. Baifukan, TokyoGoogle Scholar
  10. 10.
    Kimura M, Ohta T (1971) Theoretical aspects of population genetics. Princeton University Press, PrincetonGoogle Scholar
  11. 11.
    Kimura M, Ohta T (1969) The average number of generations until fixation of a mutant gene in a finite population. Genetics 61: 763–771PubMedGoogle Scholar
  12. 12.
    Kimura M, Ohta T (1974) On some principles governing molecular evolution. Proc Natl Acad Sci USA 71: 2848–2852PubMedCrossRefGoogle Scholar
  13. 13.
    Kimura M (1977) Preponderance of synonymous changes as evidence for the neutral theory of molecular evolution. Nature 267: 275–276PubMedCrossRefGoogle Scholar
  14. 14.
    Miyata T, Yasunaga T (1981) Rapidly evolving mouse a-globin-related pseudogene and its evolutionary history. Proc Natl Acad Sci USA 78: 450–453PubMedCrossRefGoogle Scholar
  15. 15.
    Li W-H, Gojobori T, Nei M (1981) Pseudogenes as a paradigm of neutral evolution. Nature 292: 237–239PubMedCrossRefGoogle Scholar
  16. 16.
    Wu C-I, Li W-H (1985) Evidence for higher rates of nucleotide substitution in rodents than in man. Proc Natl Acad Sci USA 82: 1741–1745PubMedCrossRefGoogle Scholar
  17. 17.
    Kikuno R, Hayashida H, Miyata T (1985) Rapid rate of rodent evolution. Proc Jpn Acad 61 (B): 153–156CrossRefGoogle Scholar
  18. 18.
    Kimura M (1987) Molecular evolutionary clock and the neutral theory. J Mol Evol 26: 24–33PubMedCrossRefGoogle Scholar
  19. 19.
    Crow JF, Kimura M (1970) An introduction to population genetics theory. Harper and Row, New York, pp 297–312Google Scholar
  20. 20.
    Hendriks W, Leunissen J, Nevo E, Bloemendal H, dejong WW (1987) The lens protein αA-crystallin of the blind mole rat, Spalax ehrenbergv. Evolutionary change and functional constraints. Proc Natl Acad Sci USA 84: 5320–5324PubMedCrossRefGoogle Scholar
  21. 21.
    Stebbins GL, Hartl DL (1988) Comparative evolution: Latent potentials for anagenetic advance. Proc Natl Acad Sci USA 85: 5141–5145PubMedCrossRefGoogle Scholar
  22. 22.
    Saitou N, Nei M (1986) Polymorphism and evolution of influenza A virus genes. Mol Biol Evol 3: 57–74PubMedGoogle Scholar
  23. 23.
    Hayashida H, Toh H, Kikuno R, Miyata T (1985) Evolution of influenza virus genes. Mol Biol Evol 2: 289–303PubMedGoogle Scholar
  24. 24.
    Gojobori T, Moriyama EN, Kimura M (in press) Molecular clock of viral evolution, and the neutral theory. Proc Natl Acad Sci USAGoogle Scholar
  25. 25.
    Gojobori T, Yokoyama S (1987) Molecular evolutionary rates of oncogenes. J Mol Evol 26: 148–156PubMedCrossRefGoogle Scholar
  26. 26.
    Yokoyama S, Gojobori T (1987) Molecular evolution and phylogeny of the human AIDS viruses LAV, HTLV-III, and ARV. J Mol Evol 24: 330–336PubMedCrossRefGoogle Scholar
  27. 27.
    Yokoyama S, Moriyama EN, Gojobori T (1987) Molecular phylogeny of the human immunodeficiency and related retroviruses. Proc Jpn Acad 63 (B): 147–150CrossRefGoogle Scholar
  28. 28.
    Penny D (1988) Origins of the AIDS virus. Nature 339: 494–495CrossRefGoogle Scholar
  29. 29.
    Li W-H, Tanimura M, Sharp PM (1988) Rates and dates of divergence between AIDS virus nucleotide sequences. Mol Biol Evol 5: 315 - 330Google Scholar
  30. 30.
    Harris H, Hopkinson DA (1972) Average heterozygosity per locus in man: An estimate based on the incidence of enzyme polymorphisms. Ann Hum Genet 36: 9–20PubMedCrossRefGoogle Scholar
  31. 31.
    Dobzhansky T (1970) Genetics of the evolutionary process. Columbia University Press, New YorkGoogle Scholar
  32. 32.
    Kimura M (1974) Gene pool of higher organisms as a product of evolution. Cold Spring Harbor Symp Quant Biol 38: 515–524PubMedGoogle Scholar
  33. 33.
    Kazazian HH Jr, Chakravarti A, Orkin SH, Antonarakis SE (1983) DNA polymorphisms in the human ß globin gene cluster. In: Nei M, Koehn RK (eds) Evolution of genes and proteins. Sinauer, Sunderland, pp 137–146Google Scholar
  34. 34.
    Nei M, Tajima F (1981) DNA polymorphism detected by restriction endonucleases. Genetics 97: 145–163PubMedGoogle Scholar
  35. 35.
    Kimura M (1983) Rare variant alleles in the light of the neutral theory. Mol Biol Evol 1: 84–93PubMedGoogle Scholar
  36. 36.
    Satta Y, Matsuura ET, Chigusa SI (1990) Mitochondrial DNA polymorphism in Drosophila melanogaster. In: Takahata N, Crow JF (eds) Population biology of genes and molecules. Baifukan, Tokyo, pp 57–73Google Scholar
  37. 37.
    Brown WM (1983) Evolution of animal mitochondrial DNA. In: Nei M, Koehn RK (eds) Evolution of genes and proteins. Sinauer, Sunderland, pp 62–88Google Scholar
  38. 38.
    Horai S (1991) Molecular phylogeny and evolution of human mitochondrial DNA. In: Kimura M, Takahata N (eds) New aspects of the genetics of molecular evolution. Japan Sci Soc. Press, Tokyo/Springer-Verlag, BerlinGoogle Scholar
  39. 39.
    Van Valen L (1974) Molecular evolution as predicted by natural selection. J Mol Evol 3: 89–101PubMedCrossRefGoogle Scholar
  40. 40.
    Watson JD, Hopkins NH, Roberts JW, Steiz JA, Weiner AM (1987) Molecular Biology of the Gene, 4th edn. Benjamin and Cummings, New YorkGoogle Scholar
  41. 41.
    Zuckerkandl E (1976) Evolutionary processes and evolutionary noise at the molecular level, II. A selectionist model for random fixations in proteins. J Mol Evol 7: 269–311PubMedCrossRefGoogle Scholar
  42. 42.
    Muto A, Yamao F, Kawauchi Y, Osawa S (1985) Codon usage in Mycoplasma capricolum. Proc Jpn Acad 61 (B): 12–15CrossRefGoogle Scholar
  43. 43.
    Yamao F, Muto A, Kawauchi Y, Iwami M, Iwagami S, Azumi Y, Osawa S (1985) UGA is read as tryptophan in Mycoplasma capricolum. Proc Natl Acad Sci USA 82: 2306–2309PubMedCrossRefGoogle Scholar
  44. 44.
    Jukes TH (1985) A change in the genetic code in Mycoplasma capricolum. J Mol Evol 22: 361–362PubMedCrossRefGoogle Scholar
  45. 45.
    Dyson F (1985) Origins of life. Cambridge University Press, CambridgeGoogle Scholar
  46. 46.
    Cairns-Smith AG (1986) Chirality and the common ancestor effect. Chem Br 22: 559–561Google Scholar

Copyright information

© Springer-Verlag Tokyo 1991

Authors and Affiliations

  1. 1.National Institute of GeneticsMishimaJapan

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