Abstract
The MHC is highly polymorphic in most vertebrates and the suggested selective mechanisms responsible for the maintenance of this variation are several, including maternal‐fetal interaction, parasite resistance, and negative-assortative mating. Evidence for these mechanisms is reviewed and estimates of the amount of selection in a number of studies are given. Although there is much yet to be understood about the mechanism and extent of balancing selection at MHC, new advances in molecular genetic technology and increasing interest in MHC from many types of biologists promise answers in the near future.
Article PDF
Similar content being viewed by others
References
Alberts, S.C. & C. Ober, 1993. Genetic variability in the major histocompatibility complex: a review of non-pathogen-mediated selective mechanisms. Yrbk. Phy. Anthrop. 36: 71-89.
Allsopp, C.E.M., A.V.S. Hill, D. Kwiakowski, A. Hughes, M. Bunce, C.J. Taylor, L. Pazmany, D. Brewster, A.J. McMichael & B.M. Greenwood, 1991. Sequence analysis of HLA-Bw53, a common West African allele, suggests an origin by gene conversion of HLA-B35. Hum. Immunol. 30: 104-109.
Apanius, V., D. Penn, P.R. Slev & L.R. Ruff, 1997. The nature of selection on the major histocompatibility complex. Crit. Rev. Immunol. 17: 179-224.
Belich, M.P., J.A. Madrigal, W.H. Hildebrand, J. Zemmour, R.C. Williams, R. Luz, M.L. Petzl-Erler & P. Parham, 1992. Unusual HLA-B alleles in two tribes of Brazilian Indians. Nature 357: 326-329.
Black, F.L. & F.M. Salzano, 1981. Evidence for heterosis in the HLA system. Amer. J. Hum. Genet. 33: 894-899.
Black, F.L. & P.W. Hedrick, 1997. Strong balancing selection at HLA loci: evidence from segregation in South Amerindian families. Proc. Natl. Acad. Sci. 94: 12452-12456.
Bodmer, W., 1972. Evolutionary significance of the HL-Asystem. Nature 237: 139-145.
Boyce, W.M., P.W. Hedrick, N.E. Muggli-Crockett, S. Kalinowski, M.C.T. Penedo & R.R. Ramey, 1997. Genetic variation of major histocompatibility complex and microsatellite loci: a comparison in bighorn sheep. Genetics 145: 421-433.
Briles, W.E., H.A. Stone & R.K. Cole, 1977. Marek's disease: effects of B histocompatibility alloalleles in resistant and susceptible chicken lines. Science 195: 193-195.
Brown, J.L. & A. Eklund, 1994. Kin recognition and the major histocompatibility complex: an integrative review. Amer. Natur. 143: 435-461.
Davenport, M.P., C.L. Quinn, R.M. Chicz, B.N. Green, A.C. Willis, W.S. Lane, J.I. Bell & A.V.S. Hill, 1995. Naturally processed peptides from two disease-resistance associated HLA-DR13 alleles show related sequence motifs and the effects of the dimorphism at position 86 of the HLA-DRb chain. Proc. Natl. Acad. Sci. 92: 6567-6571.
Doherty, P.C. & R. Zingernagel, 1975. Enhanced immunologic surveillance in mice heterozygous at the H2 complex. Nature 256: 50-52.
Edwards, S. & P.W. Hedrick, 1998. Evolution and ecology of MHC molecules: from genomics to sexual selection. Trends Ecol. Evol. 13: 305-311.
Egid, K. & J.L. Brown, 1989. The major histocompatibility complex and female mating preferences in mice. Anim. Behav. 38: 548-550.
Eklund, A., K. Egid & J.L. Brown, 1991. The major histocompatibility complex and mating preferences of male mice. Anim. Behav. 42: 693-694.
Hedrick, P.W., 1985. Genetics of Populations. Jones and Bartlett, Boston.
Hedrick, P.W., 1990. Selection at HLA: possible explanations for deficiency of homozygotes. Hum. Hered. 40: 213-220.
Hedrick, P.W., 1992. Female choice and variation in the major histocompatibility complex. Genetics 132: 575-581.
Hedrick, P.W., 1994. Evolutionary genetics of the major histocompatibility complex. Amer. Natur. 143: 945-964.
Hedrick, P.W. & F.L. Black, 1997. HLA and male selection: no evidence in South Amerindians. Amer. J. Hum. Genet. 61: 505-511.
Hedrick, P.W. & T.J. Kim, 1999. Genetics of complex polymorphisms: parasites and maintenance of MHC variation, in Evolutionary Genetics from Molecules to Morphology, edited by R. S. Singh and C. K. Krimbas. Cambridge Univ. Press, New York.
Hedrick, P.W. & E. Murray, 1983. Selection and measures of fitness, pp. 61-104 in The Genetics and Biology of Drosophila, Vol. 3d, edited by M. Ashburner, H. Carson and J. Thompson. Academic Press, New York.
Hedrick, P.W. & K.M. Parker, 1998. MHC variation in the endangered Gila topminnow. Evolution 52: 194-199..
Hedrick, P.W. & G. Thomson, 1983. Evidence for balancing selection at HLA. Genetics 104: 449-456.
Hedrick, P.W. & G. Thomson, 1988. Maternal-fetal interactions and the maintenance of HLA polymorphism. Genetics 119: 205-212.
Hedrick, P.W., G. Thomson & W. Klitz, 1987. Evolutionary genetics and HLA: another classic example. Biol. J. Linnean Soc. 31: 311-331.
Hedrick, P.W., T.S. Whittam & P. Parham, 1991. Heterozygosity at individual amino sites: extremely high levels for HLA-A and -B genes. Proc. Natl. Acad. Sci. 88: 5897-5901.
Hill, A.V.S., 1991. HLA associations with malaria in Africa: some implications for MHC evolution, pp. 403-434 in Molecular Evolution of the Major Histocompatibility Complex, edited by J. Klein and D. Klein. Springer-Verlag, Berlin.
Hill, A.V.S., C.E.M. Allsop, D. Kwiatdowski, N.M. Anstey, P. Twumasi, P.A. Rowe, S. Bennett, D. Brewster, A.J. McMichael & B.M. Greenwood, 1991. CommonWest African HLA antigens are associated with protection from severe malaria. Nature 352: 595-600.
Hill, A.V.S., S.N.R. Yates, C.E.M. Allsopp, S. Gupta, S.C. Gilbert, A. Lalvani, M. Aidoo, M. Davenport, & M. Plebanske, 1994. Human leukocyte antigens and natural selection by malaria. Phil. Trans. R. Soc. Lond. B 346: 379-385.
Hogstrand, K. & J. Bohme, 1994. A determination of the frequency of gene conversion in unmanipulated mouse sperm. Proc. Natl. Acad. Sci. 91: 9921-9925.
Hughes, A.L. & M. Nei, 1988. Pattern of nucleotide substitution at major histocompatibility complex class I loci reveals overdominant selection. Nature 335: 167-179.
Hughes, A.L. & M. Nei, 1989. Nucleotide substitution at major histocompatibility complex class II loci: evidence for overdominant selection. Proc. Natl. Acad. Sci. 86: 958-962.
Hughes, A.L. & M. Nei, 1992. Maintenance of MHC polymorphism. Nature 355: 402-403.
Jin, K., T.P. Speed & G. Thomson, 1995. Tests of random mating for a highly polymorphic locus: application to HLA data. Biometrics 51: 1064-1076.
Kingman, J.F.C., 1961. A mathematical problem in population genetics. Proc. Camb. Phil. Soc. 57: 574-582.
Lewontin, R.C., L.R. Ginsburg & S.D. Tuljapurkar, 1978. Heterosis as an explanation for large amounts of genic polymorphism. Genetics 88: 149-170.
Mandel, S.P.H., 1970. The equivalence of different sets of stability conditions for multiple allelic systems. Biometrics 26: 840- 845.
Markow, T., P.W. Hedrick, K. Zuerlein, J. Danilovs, J. Martin, T. Vyvial & C. Armstrong, 1993. HLA polymorphism in the Havasupai: evidence for balancing selection. Amer. J. Hum. Genet. 53: 943-952.
Ober, C., T. Hyslop, S. Elias, L.R. Weitkamp & W.W. Hauck, 1998. HLA matching and fetal loss: results of a 10-year prospective study. Hum. Reprod. 13: 33-38.
Ober, C., L.R. Weitkamp, N. Cox, H. Dytch, D. Kostyu & S. Elias, 1997. HLA and mate choice in humans. Am. J. Hum. Genet. 61: 497-504.
Ohta, T., 1991. Role of diversifying selection and gene conversion in evolution of major histocompatibility complex loci. Proc. Natl. Acad. Sci. 88: 6716-6720.
Okoye, R.C., E. Williams, A. Alonso, P. Doyle, H. Awad, C. Navarrete, D. Jaraquemada, W.E.R. Ollier & H. Festenstein, 1985. HLA polymorphisms in Nigerians. Tissue Antigens 25: 142-155.
Parham, P., E.J. Adams & K.L. Arnett, 1995. The origins of HLA-A, B, C polymorphism. Immunol. Rev. 143: 141-181.
Parham, P. & T. Ohta, 1996. Population biology of antigen presentation by MHC class I molecules. Science 272: 67-74.
Parham, P., K.L. Arnett, E.J. Adams, A.-M. Little, K. Tees, L.D. Barber, S.G.E. Marsh, T. Ohta, T. Markow & M.-L. Petzl-Erler, 1997. Episodic evolution and turnover of HLA-B alleles in the indigenous populations of the new world. Tissue Antigens 50: 219-232.
Parker, K.M., R.J. Sheffer & P.W. Hedrick, 1999. Molecular variation and evolutionary significant units in the endangered Gila topminnow. Cons. Biol. 13: 108-116.
Partridge, L., 1988. The rare-male effect: What is its evolutionary significance? Phil. Trans. R. Soc. Lond. B 319: 525-539.
Paterson, S. & J.M. Pemberton, 1998. No evidence for major histocompatibility complex-dependent mating patterns in a free-living ruminant population. Proc. R. Soc. Biol. 264: 1813-1819.
Plachy, J., C.-L. Chen & K. Hala, 1992. Biology of the chicken MHC (B complex). Crit. Rev. Immunol. 12: 47-79.
Potts, W.K., C.J. Manning & E.K. Wakeland, 1991. Mating patterns in seminatural populations of mice influenced by MHC genotype. Nature 352: 619-621.
Potts, W.K., C.J. Manning & E.K. Wakeland, 1994. The role of infectious disease, inbreeding and mating preferences in maintaining MHC genetic diversity: an experimental test. Phil. Trans. R. Soc. Lond. B 346: 369-378.
Ralls, K., J.D. Ballou & A. Templeton, 1988. Estimates of lethal equivalents and the cost of inbreeding in mammals. Cons. Biol. 2: 185-193.
Ralls, K., P.H. Harvey & A.M. Lyles, 1986. Inbreeding in natural population of birds and mammals, pp. 25-56 in Conservation Biology: The Science of Scarcity and Diversity, edited by M.E. Soule. Sinauer Assoc., Sunderland, MA.
Ritte, U., E. Neufeld, C. O'hUigin, F. Figeroa & J. Klein, 1991. Origins of H-2 polymorphism in the house mouse: II. Characterization of amodel population and evidence for heterozygous advantage. Immunogenetics 34: 164-173.
Rosenberg, L.T., D. Cooperman & R. Payne, 1983. HLA and mate selection. Immunogenetics 17: 89-93.
Satta, Y., C. O'hUigin, N. Takahata, & J. Klein, 1994. Intensity of natural selection at the major histocompatibility complex loci. Proc. Natl. Acad. Sci. 91: 7184-7188.
Spencer, H.G. & R.W. Marks, 1988. The maintenance of singlelocus polymorphism: I. Numerical studies of a viability selection model. Genetics 120: 605-613.
Takahata, N. & M. Nei, 1990. Allelic geneology under overdominant and frequency-dependent selection and polymorphism of major histocompatibility complex loci. Genetics 124: 967-978.
Takahata, N., Y. Satta & J. Klein, 1992. Polymorphism and balancing selection at major histocompatibility complex loci. Genetics 130: 925-938.
Thomas, M.L., J.H. Harger, D.K. Wagener, B.S. Rabin & T.J. Gill, 1985. HLA sharing and spontaneous abortion in humans. Amer. J. Obstet. Gynec. 151: 1053-1058.
Thursz, M.R., H.C. Thomas, B.M. Greenwood & A.V.S. Hill, 1997. Heterozygote advantage for HLA class-II type in hepatitis B virus infection. Nat. Genet. 17: 11-12.
von Schantz, T., H. Wittzell, G. Goransson, M. Grahn & K. Persson, 1996. MHC genotype and male ornamentation: genetic evidence for the Hamilton-Zuk model. Proc. R. Soc. Lond. B 263: 265-271.
Watkins, D.I., S.N. McAdam, X. Liu, C.R. Strang, E.L. Milford, C.G. Levine, T.L. Garber, A.L. Dogon, C.I. Lord, S.H. Ghim, G.M. Troup, A.L. Hughes & N.L. Letvin, 1992. Newrecombinant HLA-B alleles in a tribe of South American Amerindians indicate rapid evolution of MHC class I loci. Nature 357: 329-333.
Yamazaki, K., G.K. Beauchamp, D. Kupniewski, J. Bard, L. Thomas & E.A. Boyse, 1988. Familial imprinting determines H-2 selective mating preferences. Science 240: 1331-1332.
Zangenberg, G., M.-M. Huang, N. Arnheim & H. Erlich, 1995. New HLA-DPB1 alleles generated by interallelic gene conversion detected by analysis of sperm. Natur. Genet. 10: 407-414.
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hedrick, P.W. Balancing selection and MHC. Genetica 104, 207–214 (1998). https://doi.org/10.1023/A:1026494212540
Issue Date:
DOI: https://doi.org/10.1023/A:1026494212540