Pathogen resistance and genetic variation at MHC loci

Philip W. Hedrick

Research output: Contribution to journalArticle

260 Citations (Scopus)

Abstract

Balancing selection in the form of heterozygote advantage, frequency-dependent selection, or selection that varies in time and/or space, has been proposed to explain the high variation at major histocompatibility complex (MHC) genes. Here the effect of variation of the presence and absence of pathogens over time on genetic variation at multiallelic loci is examined. In the basic model, resistance to each pathogen is conferred by a given allele, and this allele is assumed to be dominant. Given that s is the selective disadvantage for homozygotes (and heterozygotes) without the resistance allele and the proportion of generations, which a pathogen is present, is e, fitnesses for homozygotes become (1 - s)(n-1)e and the fitnesses for heterozygotes become (1 - s)(n-2)e, where n is the number of alleles. In this situation, the conditions for a stable, multiallelic polymorphism are met even though there is no intrinsic heterozygote advantage. The distribution of allele frequencies and consequently heterozygosity are a function of the autocorrelation of the presence of the pathogen in subsequent generations. When there is a positive autocorrelation over generations, the observed heterozygosity is reduced. In addition, the effects of lower levels of selection and dominance and the influence of genetic drift were examined. These effects were compared to the observed heterozygosity for two MHC genes in several South American Indian samples. Overall, resistance conferred by specific alleles to temporally variable pathogens may contribute to the observed polymorphism at MHC genes and other similar host defense loci.

Original languageEnglish (US)
Pages (from-to)1902-1908
Number of pages7
JournalEvolution
Volume56
Issue number10
StatePublished - Oct 1 2002

Fingerprint

major histocompatibility complex
Major Histocompatibility Complex
genetic variation
Heterozygote
heterozygosity
allele
pathogen
Alleles
loci
pathogens
alleles
Homozygote
South American Indians
autocorrelation
homozygosity
gene
Genes
polymorphism
fitness
Genetic Drift

Keywords

  • Frequency-dependent selection
  • Heterozygote advantage
  • HLA loci
  • Overdominance
  • Polymorphism

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Ecology, Evolution, Behavior and Systematics
  • Agricultural and Biological Sciences (miscellaneous)
  • Genetics(clinical)
  • Ecology
  • Genetics

Cite this

Hedrick, P. W. (2002). Pathogen resistance and genetic variation at MHC loci. Evolution, 56(10), 1902-1908.

Pathogen resistance and genetic variation at MHC loci. / Hedrick, Philip W.

In: Evolution, Vol. 56, No. 10, 01.10.2002, p. 1902-1908.

Research output: Contribution to journalArticle

Hedrick, PW 2002, 'Pathogen resistance and genetic variation at MHC loci', Evolution, vol. 56, no. 10, pp. 1902-1908.
Hedrick PW. Pathogen resistance and genetic variation at MHC loci. Evolution. 2002 Oct 1;56(10):1902-1908.
Hedrick, Philip W. / Pathogen resistance and genetic variation at MHC loci. In: Evolution. 2002 ; Vol. 56, No. 10. pp. 1902-1908.
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