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Evolution of the Human Leukocyte Antigen System

Gaudieri, S. and John, M. (2017) Evolution of the Human Leukocyte Antigen System. In: Tibayrenc, M. and Ayala, F.J., (eds.) On Human Nature. Elsevier Inc., pp. 211-219.

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Item Type: Book Chapter
Murdoch Affiliation(s): Institute for Immunology and Infectious Diseases
Publisher: Elsevier Inc.
Copyright: © 2017 Elsevier Inc.
Other Information: The human leukocyte antigen (HLA) genes in modern human populations reflect an intricate coevolution with pathogens that has occurred over millennia. These genes encode proteins involved in the presentation of self and nonself peptides to immune cells, and this sampling process allows for the detection of foreign infections, immunological memory, and immune surveillance but can also lead to adverse reactions resulting in autoimmunity and hypersensitivity. Not surprisingly, HLA genes are commonly associated with differential outcomes to infections and inflammatory diseases. At the genomic level, the HLA genes reside within the major histocompatibility complex (MHC) on the short arm of chromosome six. This region is characterized by high levels of polymorphism due to positive selection and segmental duplications giving rise to closely related proteins with overlapping function and extensive linkage disequilibrium spanning several megabases of sequence resulting in the inheritance, en bloc, of combinations of specific alleles or haplotypes. Although some of these features can be observed elsewhere in the human genome, the MHC lies on one extreme of the spectrum. Regions containing homologous genes of the HLA system in nonhuman primates exhibit a similar pattern with additional lineage-specific modifications. This chapter will cover the evolution of the human MHC, focusing on the HLA class I genes.
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