Skip to main content
Genetics logoLink to Genetics
. 1991 May;128(1):183–192. doi: 10.1093/genetics/128.1.183

A Study on a Nearly Neutral Mutation Model in Finite Populations

H Tachida 1
PMCID: PMC1204447  PMID: 2060776

Abstract

As a nearly neutral mutation model, the house-of-cards model is studied in finite populations using computer simulations. The distribution of the mutant effect is assumed to be normal. The behavior is mainly determined by the product of the population size, N, and the standard deviation, σ, of the distribution of the mutant effect. If 4Nσ is large compared to one, a few advantageous mutants are quickly fixed in early generations. Then most mutation becomes deleterious and very slow increase of the average selection coefficient follows. It takes very long for the population to reach the equilibrium state. Substitutions of alleles occur very infrequently in the later stage. If 4Nσ is the order of one or less, the behavior is qualitatively similar to that of the strict neutral case. Gradual increase of the average selection coefficient occurs and in generations of several times the inverse of the mutation rate the population almost reaches the equilibrium state. Both advantageous and neutral (including slightly deleterious) mutations are fixed. Except in the early stage, an increase of the standard deviation of the distribution of the mutant effect decreases the average heterozygosity. The substitution rate is reduced as 4Nσ is increased. Three tests of neutrality, one using the relationship between the average and the variance of heterozygosity, another using the relationship between the average heterozygosity and the average number of substitutions and Watterson's homozygosity test are applied to the consequences of the present model. It is found that deviation from the neutral expectation becomes apparent only when 4Nσ is more than two. Also a simple approximation for the model is developed which works well when the mutation rate is very small.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aquadro C. F., Lado K. M., Noon W. A. The rosy region of Drosophila melanogaster and Drosophila simulans. I. Contrasting levels of naturally occurring DNA restriction map variation and divergence. Genetics. 1988 Aug;119(4):875–888. doi: 10.1093/genetics/119.4.875. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bowie J. U., Reidhaar-Olson J. F., Lim W. A., Sauer R. T. Deciphering the message in protein sequences: tolerance to amino acid substitutions. Science. 1990 Mar 16;247(4948):1306–1310. doi: 10.1126/science.2315699. [DOI] [PubMed] [Google Scholar]
  3. Choudhary M., Singh R. S. A Comprehensive Study of Genic Variation in Natural Populations of Drosophila melanogaster. III. Variations in Genetic Structure and Their Causes between Drosophila melanogaster and Its Sibling Species Drosophila simulans. Genetics. 1987 Dec;117(4):697–710. doi: 10.1093/genetics/117.4.697. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cockerham C. C., Tachida H. Evolution and maintenance of quantitative genetic variation by mutations. Proc Natl Acad Sci U S A. 1987 Sep;84(17):6205–6209. doi: 10.1073/pnas.84.17.6205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dean A. M., Dykhuizen D. E., Hartl D. L. Fitness effects of amino acid replacements in the beta-galactosidase of Escherichia coli. Mol Biol Evol. 1988 Sep;5(5):469–485. doi: 10.1093/oxfordjournals.molbev.a040513. [DOI] [PubMed] [Google Scholar]
  6. Fuerst P. A., Chakraborty R., Nei M. Statistical studies on protein polymorphism in natural populations. I. Distribution of single locus heterozygosity. Genetics. 1977 Jun;86(2 Pt 1):455–483. [PMC free article] [PubMed] [Google Scholar]
  7. Hudson R. R., Kreitman M., Aguadé M. A test of neutral molecular evolution based on nucleotide data. Genetics. 1987 May;116(1):153–159. doi: 10.1093/genetics/116.1.153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. KIMURA M., CROW J. F. THE NUMBER OF ALLELES THAT CAN BE MAINTAINED IN A FINITE POPULATION. Genetics. 1964 Apr;49:725–738. doi: 10.1093/genetics/49.4.725. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. KIMURA M. On the probability of fixation of mutant genes in a population. Genetics. 1962 Jun;47:713–719. doi: 10.1093/genetics/47.6.713. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Kimura M. Evolutionary rate at the molecular level. Nature. 1968 Feb 17;217(5129):624–626. doi: 10.1038/217624a0. [DOI] [PubMed] [Google Scholar]
  11. Kimura M. Model of effectively neutral mutations in which selective constraint is incorporated. Proc Natl Acad Sci U S A. 1979 Jul;76(7):3440–3444. doi: 10.1073/pnas.76.7.3440. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Kimura M. Molecular evolutionary clock and the neutral theory. J Mol Evol. 1987;26(1-2):24–33. doi: 10.1007/BF02111279. [DOI] [PubMed] [Google Scholar]
  13. Kimura M., Takahata N. Selective constraint in protein polymorphism: study of the effectively neutral mutation model by using an improved pseudosampling method. Proc Natl Acad Sci U S A. 1983 Feb;80(4):1048–1052. doi: 10.1073/pnas.80.4.1048. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kreitman M. E., Aguadé M. Excess polymorphism at the Adh locus in Drosophila melanogaster. Genetics. 1986 Sep;114(1):93–110. doi: 10.1093/genetics/114.1.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Li W. H. Maintenance of Genetic Variability under the Joint Effect of Mutation, Selection and Random Drift. Genetics. 1978 Oct;90(2):349–382. doi: 10.1093/genetics/90.2.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Ohta T. Population size and rate of evolution. J Mol Evol. 1972;1(3):305–314. [PubMed] [Google Scholar]
  17. Ohta T. Slightly deleterious mutant substitutions in evolution. Nature. 1973 Nov 9;246(5428):96–98. doi: 10.1038/246096a0. [DOI] [PubMed] [Google Scholar]
  18. Perutz M. F. Species adaptation in a protein molecule. Mol Biol Evol. 1983 Dec;1(1):1–28. doi: 10.1093/oxfordjournals.molbev.a040299. [DOI] [PubMed] [Google Scholar]
  19. Takahata N. On the overdispersed molecular clock. Genetics. 1987 May;116(1):169–179. doi: 10.1093/genetics/116.1.169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Ward R. D., Skibinski D. O. Observed relationships between protein heterozygosity and protein genetic distance and comparisons with neutral expectations. Genet Res. 1985 Jun;45(3):315–340. doi: 10.1017/s0016672300022291. [DOI] [PubMed] [Google Scholar]
  21. Zeng Z. B., Tachida H., Cockerham C. C. Effects of mutation on selection limits in finite populations with multiple alleles. Genetics. 1989 Aug;122(4):977–984. doi: 10.1093/genetics/122.4.977. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Genetics are provided here courtesy of Oxford University Press

RESOURCES