Major histocompatibility complex (MHC) genes code for cell surface proteins that facilitate an organism's immune response to pathogens as well as its ability to avoid attacking its own cells. These genes have maintained an unusually high level of allelic diversity throughout time and throughout different populations. This means that for each MHC gene, many alleles (or gene variants) consistently exist within the population, and many individuals are heterozygous at MHC loci (meaning they possess two different alleles for a given gene locus).
The vast source of genetic variation affecting an organism's fitness stems from the co-evolutionary arms race between hosts and parasites. There are two hypotheses for explaining the MHC's high diversity, which are not mutually exclusive. One is that there is selection for individuals to possess a diverse set of MHC alleles, which would occur if MHC heterozygotes are more resistant to pathogens than homozygotes—this is called heterozygote advantage. The second is that there is selection that undergoes a frequency-dependent cycle—this is called the Red Queen hypothesis.
There is evidence that many vertebrates, including humans, select their mates based on signals of "compatibility" between their MHC alleles, with a preference for mates with different alleles than their own, resulting in pairings that would tend to produce more heterozygous offspring. There are several proposed hypotheses that address how MHC-associated mating preferences could be adaptive and how an unusually large amount of allelic diversity has been maintained in the MHC.[1][2]
Milinski
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