THE ROLE OF INFECTIOUS-DISEASE, INBREEDING AND MATING PREFERENCES IN MAINTAINING MHC GENETIC DIVERSITY - AN EXPERIMENTAL TEST

In house mice, and probably most mammals, major histocompatibility com plex (MHC) gene products influence both immune recognition and individ ual odours in an allele-specific fashion. Although it is generally ass umed that some form of pathogen-driven balancing selection is responsi ble for the unprecedented genetic diversity of MHC genes, the MHC-base d mating preferences observed in house mice are sufficient to account for the genetic diversity of MHC genes found in this and other vertebr ates. These MHC disassortative mating preferences are completely consi stent with the conventional view that pathogen-driven MHC heterozygote advantage operates on MHC genes. This is because such matings prefere ntially produce MHC-heterozygours progeny, which could enjoy enhanced disease resistance. However, such matings could also function to avoid genome-wide inbreeding. To discriminate between these two hypotheses we measured the fitness consequences of both experimentally manipulate d levels of inbreeding and MHC homozygosity and heterozygosity in semi -natural populations of wild-derived house mice. We were able to measu re a fitness decline associated with inbreeding, but were unable to de tect fitness declines associated with MHC homozygosity. These data sug gest that inbreeding avoidance may be the most important function of M HC-based mating preferences and therefore the fundamental selective fo rce diversifying MHC genes in species with such mating patterns. Altho ugh controversial, this conclusion is consistent with the majority of the data from the inbreeding and immunological literature.