• We are sorry, but NCBI web applications do not support your browser and may not function properly. More information
Logo of geneticsGeneticsCurrent IssueInformation for AuthorsEditorial BoardSubscribeSubmit a Manuscript
Genetics. Dec 2000; 156(4): 2119–2126.
PMCID: PMC1461383

A method for estimating the intensity of overdominant selection from the distribution of allele frequencies.


A method is proposed for estimating the intensity of overdominant selection scaled by the effective population size, S = 2Ns, from allele frequencies. The method is based on the assumption that, with strong overdominant selection, allele frequencies are nearly at their deterministic equilibrium values and that, to a first approximation, deviations depend only on S. Simulations verify that reasonably accurate estimates of S can be obtained for realistic sample sizes. The method is applied to data from several loci in the major histocompatibility complex (Mhc) in numerous human populations. For alleles distinguished by both serological typing and the sequence of the peptide-binding region, our estimates of S are comparable to those obtained by analysis of DNA sequences in showing that selection is strongest on HLA-B and weaker on HLA-A, HLA-DRB1, and HLA-DQA1. The intensity of selection on HLA-B varied considerably among populations. Two populations, Native American and Inuit, showed an excess rather than a deficiency in homozygosity. Comparable estimates of S were obtained for alleles at Mhc class II loci distinguished by serological reactions (serotyping) and by differences in the amino acid sequences of the peptide-binding region (molecular typing). A comparison of two types of data for DQA1 and DRB1 showed that serotyping led to generally lower estimates of S.

Full Text

The Full Text of this article is available as a PDF (211K).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.
  • Hughes AL, Yeager M. Natural selection at major histocompatibility complex loci of vertebrates. Annu Rev Genet. 1998;32:415–435. [PubMed]
  • Satta Y. Effects of intra-locus recombination of HLA polymorphism. Hereditas. 1997;127(1-2):105–112. [PubMed]
  • Satta Y, O'hUigin C, Takahata N, Klein J. Intensity of natural selection at the major histocompatibility complex loci. Proc Natl Acad Sci U S A. 1994 Jul 19;91(15):7184–7188. [PMC free article] [PubMed]
  • Slatkin M. An exact test for neutrality based on the Ewens sampling distribution. Genet Res. 1994 Aug;64(1):71–74. [PubMed]
  • Slatkin M. A correction to the exact test based on the Ewens sampling distribution. Genet Res. 1996 Dec;68(3):259–260. [PubMed]
  • Slatkin M, Muirhead CA. Overdominant alleles in a population of variable size. Genetics. 1999 Jun;152(2):775–781. [PMC free article] [PubMed]
  • Takahata N. A simple genealogical structure of strongly balanced allelic lines and trans-species evolution of polymorphism. Proc Natl Acad Sci U S A. 1990 Apr;87(7):2419–2423. [PMC free article] [PubMed]
  • Valdes AM, McWeeney SK, Meyer D, Nelson MP, Thomson G. Locus and population specific evolution in HLA class II genes. Ann Hum Genet. 1999 Jan;63(Pt 1):27–43. [PubMed]
  • Watterson GA. Heterosis or neutrality? Genetics. 1977 Apr;85(4):789–814. [PMC free article] [PubMed]

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


Related citations in PubMed

See reviews...See all...

Cited by other articles in PMC

See all...


  • MedGen
    Related information in MedGen
  • PubMed
    PubMed citations for these articles

Recent Activity

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...