The Nature of Selection on the Major Histocompatibility Complex

被引:23
作者
Apanius, Victor [1 ,2 ]
Penn, Dustin [3 ,4 ]
Slev, Patricia R. [5 ]
Ruff, L. Ramelle [5 ]
Potts, Wayne K. [4 ,5 ]
机构
[1] McGill Univ, Inst Parasitol, Macdonald Coll, 21,111 Lakeshore Rd, Ste Anne De Bellevue, PQ H9X 3V9, Canada
[2] Florida Int Univ, Dept Biol Sci, Univ Pk, Miami, FL 33199 USA
[3] Univ Florida, Dept Zool, Gainesville, FL 32611 USA
[4] Univ Utah, Dept Biol, Salt Lake City, UT 84112 USA
[5] Univ Florida, Dept Pathol & Lab Med, Gainesville, FL 32610 USA
关键词
host-parasite coevolution; immunogenetics; sexual selection; kin recognition; odor; life history; MHC CLASS-I; HUMAN-LEUKOCYTE ANTIGEN; FREQUENCY-DEPENDENT SELECTION; MATERNAL-FETAL INTERACTIONS; RESTRICTED T-CELLS; KNOCK-OUT MICE; MATING PREFERENCES; IMMUNE-RESPONSE; GENETIC-CONTROL; HLA-DR;
D O I
10.1615/CritRevImmunol.v37.i2-6.10
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Only natural selection can account for the extreme genetic diversity of genes of the major histocompatibility complex (MHC). Although the structure and function of classic MHC genes is well understood at the molecular and cellular levels, there is controversy about how MHC diversity is selectively maintained. The diversifying selection can be driven by pathogen interactions and inbreeding avoidance mechanisms. Pathogen-driven selection can maintain MHC polymorphism based on heterozygote advantage or frequency-dependent selection due to pathogen evasion of MHC-dependent immune recognition. Empirical evidence demonstrates that specific MHC haplotypes are resistant to certain infectious agents, while susceptible to others. These data are consistent with both heterozygote advantage and frequency-dependent models. Additional research is needed to discriminate between these mechanisms. Infectious agents can precipitate autoimmunity and can potentially contribute to MHC diversity through molecular mimicry and by favoring immunodominance. MHC-dependent abortion and mate choice, based on olfaction, can also maintain MHC diversity and probably functions both to avoid genome-wide inbreeding and produce MHC-heterozygous offspring with increased immune responsiveness. Although this diverse set of hypotheses are often treated as competing alternatives, we believe that they all fit into a coherent, internally consistent thesis. It is likely that at least in some species, all of these mechanisms operate, leading to the extreme diversification found in MHC genes.
引用
收藏
页码:75 / 120
页数:46
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