Skip to main content
NCBI home page
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1991 Aug 1;88(15):6716–6720. doi: 10.1073/pnas.88.15.6716

Role of diversifying selection and gene conversion in evolution of major histocompatibility complex loci.

T Ohta 1
PMCID: PMC52159  PMID: 1862096

Abstract

Genes at the major histocompatibility complex (MHC) in mammals are known to have exceptionally high polymorphism and linkage disequilibrium. In addition, these genes form highly complicated gene families that have evolved through gene conversion and unequal crossing-over. It has been shown recently that amino acid substitution at the antigen recognition site (ARS) is more rapid than synonymous substitution, suggesting some kind of positive natural selection working at the ARS. It is highly desirable to know the interactive effect of gene conversion and natural selection on the evolution and variation of MHC gene families. A population genetic model is constructed that incorporates both selection and gene conversion. Diversifying selection is assumed in which sequence diversity is enhanced not only between alleles at the same locus but also between duplicated genes. Expressed and nonexpressed loci are assumed as in the class I gene family of MHC, with gene conversion occurring among all loci. Extensive simulation studies reveal that very weak selection at individual amino acid sites in combination with gene conversion can explain the unusual pattern of evolution and polymorphisms. Here both gene conversion and natural selection contribute to enhancing polymorphism.

Full text

PDF
6716

Selected References

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

  1. Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. Structure of the human class I histocompatibility antigen, HLA-A2. Nature. 1987 Oct 8;329(6139):506–512. doi: 10.1038/329506a0. [DOI] [PubMed] [Google Scholar]
  2. Bjorkman P. J., Saper M. A., Samraoui B., Bennett W. S., Strominger J. L., Wiley D. C. The foreign antigen binding site and T cell recognition regions of class I histocompatibility antigens. Nature. 1987 Oct 8;329(6139):512–518. doi: 10.1038/329512a0. [DOI] [PubMed] [Google Scholar]
  3. Bodmer J. G., Bodmer W. F. Studies on African Pygmies. IV. A comparative study of the HL-A polymorphism in the Babinga Pygmies and other African and Caucasian populations. Am J Hum Genet. 1970 Jul;22(4):396–411. [PMC free article] [PubMed] [Google Scholar]
  4. Brégégère F. A directional process of gene conversion is expected to yield dynamic polymorphism associated with stability of alternative alleles in class I histocompatibility antigens gene family. Biochimie. 1983 Apr-May;65(4-5):229–237. doi: 10.1016/s0300-9084(83)80274-0. [DOI] [PubMed] [Google Scholar]
  5. Franklin I., Lewontin R. C. Is the gene the unit of selection? Genetics. 1970 Aug;65(4):707–734. doi: 10.1093/genetics/65.4.707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hedrick P. W. Gametic disequilibrium measures: proceed with caution. Genetics. 1987 Oct;117(2):331–341. doi: 10.1093/genetics/117.2.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hughes A. L., Nei M. Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature. 1988 Sep 8;335(6186):167–170. doi: 10.1038/335167a0. [DOI] [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. Kappes D., Strominger J. L. Human class II major histocompatibility complex genes and proteins. Annu Rev Biochem. 1988;57:991–1028. doi: 10.1146/annurev.bi.57.070188.005015. [DOI] [PubMed] [Google Scholar]
  10. Klein J., Figueroa F. Evolution of the major histocompatibility complex. Crit Rev Immunol. 1986;6(4):295–386. [PubMed] [Google Scholar]
  11. Klein J. Origin of major histocompatibility complex polymorphism: the trans-species hypothesis. Hum Immunol. 1987 Jul;19(3):155–162. doi: 10.1016/0198-8859(87)90066-8. [DOI] [PubMed] [Google Scholar]
  12. Lawlor D. A., Zemmour J., Ennis P. D., Parham P. Evolution of class-I MHC genes and proteins: from natural selection to thymic selection. Annu Rev Immunol. 1990;8:23–63. doi: 10.1146/annurev.iy.08.040190.000323. [DOI] [PubMed] [Google Scholar]
  13. Nadeau J. H., Wakeland E. K., Götze D., Klein J. The population genetics of the H-2 polymorphism in European and North African populations of the house mouse (Mus musculus L.). Genet Res. 1981 Feb;37(1):17–31. doi: 10.1017/s0016672300019984. [DOI] [PubMed] [Google Scholar]
  14. Nagylaki T. The evolution of multigene families under intrachromosomal gene conversion. Genetics. 1984 Mar;106(3):529–548. doi: 10.1093/genetics/106.3.529. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Ohta T. Linkage disequilibrium between amino acid sites in immunoglobulin genes and other multigene families. Genet Res. 1980 Oct;36(2):181–197. doi: 10.1017/s0016672300019790. [DOI] [PubMed] [Google Scholar]
  16. Ohta T. On the evolution of multigene families. Theor Popul Biol. 1983 Apr;23(2):216–240. doi: 10.1016/0040-5809(83)90015-1. [DOI] [PubMed] [Google Scholar]
  17. Ohta T. Some models of gene conversion for treating the evolution of multigene families. Genetics. 1984 Mar;106(3):517–528. doi: 10.1093/genetics/106.3.517. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Parham P. MHC protein structure. Getting into the groove. Nature. 1989 Dec 7;342(6250):617–618. doi: 10.1038/342617a0. [DOI] [PubMed] [Google Scholar]
  19. Takahata N., Nei M. Allelic genealogy under overdominant and frequency-dependent selection and polymorphism of major histocompatibility complex loci. Genetics. 1990 Apr;124(4):967–978. doi: 10.1093/genetics/124.4.967. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES