Major Histocompatibility Complex (MHC) Genes: Evolution


The major histocompatibility complex is a family of genes whose products play a key role in the immune system, presenting peptides to T cells. This family includes the most polymorphic loci known in animals.

Keywords: human leukocyte antigen; immune system genes; major histocompatibility complex; multigene families; polymorphism

Figure 1.

Map of the human class II (a) and class I (b) regions of the major histocompatibility complex, showing expressed class I and class II genes only. Distances are in kilobases. Dark boxes are highly polymorphic loci.

Figure 2.

Schematic drawings of class I and class II molecules of the major histocompatibility complex. PBR: peptide‐binding region; β2m: β2‐microglobulin.



Bjorkman PJ, Saper MA, Samraoui B et al. (1987) Structure of the human class I histocompatibility antigen, HLA‐A2. Nature 329: 506–512.

Brown JH, Jardetsky T, Saper MA et al. (1993) Three‐dimensional structure of the human class II histocompatibility antigen HLA‐DR1. Nature 364: 33–39.

Cadavid LF, Shufflebotham C, Ruiz FJ et al. (1997) Evolutionary instability of the major histocompatibility complex class I loci in New World primates. Proceedings of the National Academy of Sciences of the United States of America 94: 14536–14541.

Carrington M, Nelson GW, Martin MP et al. (1999) HLA and HIV‐1: heterozygote advantage and B*35‐Cw*04 disadvantage. Science 283: 1748–1752.

Cereb N, Hughes AL and Yang SY (1997) Locus‐specific conservation of the HLA class I introns by intralocus recombination. Immunogenetics 47: 30–36.

Doherty PC and Zinkernagel RM (1975) Enhanced immunologic surveillance in mice heterozygous at the H‐2 gene complex. Nature 256: 50–52.

Hedrick PW and Thompson G (1983) Evidence for balancing selection at HLA. Genetics 104: 449–456.

Hughes AL and Nei M (1988) Pattern of nucleotide substitution at MHC class I loci reveals overdominant selection. Nature 335: 167–170.

Hughes AL and Nei M (1989) Evolution of the major histocompatibility complex: independent origin of nonclassical class I genes in different groups of mammals. Molecular Biology and Evolution 6: 559–579.

Mayer WE, Jonker D, Klein D et al. (1988) Nucleotide sequence of chimpanzee MHC class I alleles: evidence for transspecies mode of evolution. EMBO Journal 7: 2765–2774.

Further Reading

Bontrop RE (2006) Comparative genetics of MHC polymorphisms in different primate species: duplications and deletions. Human Immunology 67: 388–397.

Flajnik MF, Ohta Y, Namikawa‐Yamada C and Nonaka M (1999) Insight into the primordial MHC from studies in ectothermic vertebrates. Immunological Reviews 167: 59–67.

Hughes AL (1999) Adaptive Evolution of Genes and Genomes. New York, NY: Oxford University Press.

Hughes AL, Hughes MK, Howell CY and Nei M (1994) Natural selection at the class II major histocompatibility complex loci of mammals. Philosophical Transactions of the Royal Society of London B 345: 359–367.

Hughes AL and Nei M (1990) Evolutionary relationships of class II MHC genes in mammals. Molecular Biology and Evolution 7: 491–514.

Hughes AL and Yeager M (1998) Natural selection at the major histocompatibility complex loci of vertebrates. Annual Review of Genetics 32: 415–435.

Hughes AL, Yeager M, Ten Elshof A and Chorney MJ (1999) A new taxonomy of mammalian MHC class I molecules. Immunology Today 20: 22–26.

Kelley J, Walter L and Trowsdale J (2005) Comparative genomics of major histocompatibility complexes. Immunogenetics 56: 683–695.

Klein J (1986) Natural History of the Major Histocompatibility Complex. New York, NY: Wiley.

McDevitt HO (2000) Discovering the role of the major histocompatibility complex in the immune response. Annual Review of Immunology 18: 1–17.

Meyer D, Single RM, Mack SJ, Erlich HA and Thomson G (2006) Signatures of demographic history and natural selection in the human major histocompatibility complex loci. Genetics 173: 2121–2142.

Nei M, Gu X and Sitnikova T (1997) Evolution by the birth‐and‐death process in multigene families of the vertebrate immune system. Proceedings of the National Academy of Sciences of the United States of America 94: 7799–7806.

Parham P and Ohta T (1996) Population biology of antigen presentation by MHC class I molecules. Science 272: 67–74.

Shiina T, Ota M, Shimizu S et al. (2006) Rapid evolution of major histocompatibility complex class I genes in primates generates new disease alleles in humans via hitchhiking diversity. Genetics 173: 1555–1570.

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How to Cite close
Hughes, Austin L(Apr 2008) Major Histocompatibility Complex (MHC) Genes: Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005133.pub2]