Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. 1978 Oct; 90(2): 349–382.
PMCID: PMC1213895

Maintenance of Genetic Variability under the Joint Effect of Mutation, Selection and Random Drift


Formulae are developed for the distribution of allele frequencies (the frequency spectrum), the mean number of alleles in a sample, and the mean and variance of heterozygosity under mutation pressure and under either genic or recessive selection. Numerical computations are carried out by using these formulae and Watterson's (1977) formula for the distribution of allele frequencies under overdominant selection. The following properties are observed: (1) The effect of selection on the distribution of allele frequencies is slight when 4Ns ≤ 4, but becomes strong when 4Ns becomes larger than 10, where N denotes the effective size and s the selective difference between alleles. Genic selection and recessive selection tend to force the distribution to be U-shaped, whereas overdominant selection has the opposite tendency. (2) The mean total number of alleles in a sample is much more strongly affected by selection than the mean number of rare alleles in a sample. (3) Even slight heterozygote advantage, as small as 10-5, increases considerably the mean heterozygosity of a population, as compared to the case of neutral mutations. On the other hand, even slight genic or recessive selection causes a great reduction in heterozygosity when population size is large. (4) As a test statistic, the variance of heterozygosity can be used to detect the presence of selection, though it is not efficient when the selection intensity is very weak, say when 4Ns is around 4 or less. A model, which is somewhat similar to Ohta's (1976) model of slightly deleterious mutations, has been proposed to explain the following general patterns of genic variation: (i) There seems to be an upper limit for the observed average heterozygosities. (ii) The distribution of allele frequencies is U-shaped for every species surveyed. (iii) Most of the species surveyed tend to have an excess of rare alleles as compared with that expected under the neutral mutation hypothesis.

Full Text

The Full Text of this article is available as a PDF (2.0M).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Ayala FJ, Tracey ML, Barr LG, McDonald JF, Pérez-Salas S. Genetic variation in natural populations of five Drosophila species and the hypothesis of the selective neutrality of protein polymorphisms. Genetics. 1974 Jun;77(2):343–384. [PMC free article] [PubMed]
  • Fuerst PA, 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]
  • KIMURA M. Stochastic processes and distribution of gene frequencies under natural selection. Cold Spring Harb Symp Quant Biol. 1955;20:33–53. [PubMed]
  • Kimura M, Ohta T. Distribution of allelic frequencies in a finite population under stepwise production of neutral alleles. Proc Natl Acad Sci U S A. 1975 Jul;72(7):2761–2764. [PMC free article] [PubMed]
  • Li WH, Nei M. Drift variances of heterozygosity and genetic distance in transient states. Genet Res. 1975 Jun;25(3):229–248. [PubMed]
  • Nei M, Chakraborty R, Fuerst PA. Infinite allele model with varying mutation rate. Proc Natl Acad Sci U S A. 1976 Nov;73(11):4164–4168. [PMC free article] [PubMed]
  • Nei M, Li WH. The transient distribution of allele frequencies under mutation pressure. Genet Res. 1976 Dec;28(3):205–214. [PubMed]
  • Ohta T. Role of very slightly deleterious mutations in molecular evolution and polymorphism. Theor Popul Biol. 1976 Dec;10(3):254–275. [PubMed]
  • Watterson GA. The homozygosity test of neutrality. Genetics. 1978 Feb;88(2):405–417. [PMC free article] [PubMed]

Articles from Genetics are provided here courtesy of Genetics Society of America


Save items

Cited by other articles in PMC

See all...


  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...