What evolutionary processes maintain MHCIIβ diversity within and among populations of stickleback?

Major Histocompatibility Complex (MHC) genes encode for proteins that
recognize foreign protein antigens to initiate T-cell mediated adaptive
immune responses. They are often the most polymorphic genes in vertebrate
genomes. How evolution maintains this diversity is still an unsettled
issue. Three main hypotheses seek to explain the maintenance of MHC
diversity by invoking pathogen-mediated selection: heterozygote advantage,
frequency-dependent selection, and fluctuating selection across landscapes
or through time. Here, we use a large-scale field parasite survey in a
stickleback metapopulation to test predictions derived from each of these
hypotheses. We identify over a thousand MHCIIβ variants (alleles spanning
paralogous genes) and find that many of them covary positively or
negatively with parasite load, suggesting that these genes contribute to
resistance or susceptibility. However, despite our large sample-size, we
find no evidence for the widely-cited stabilizing selection on MHC
heterozygosity, in which individuals with an intermediate number of MHC
variants have the lowest parasite burden. Nor do we observe a rare-variant
advantage, or widespread fluctuating selection across populations. In
contrast, we find that MHC diversity is best predicted by neutral
genome-wide heterozygosity and between-population genomic divergence,
suggesting neutral processes are important in shaping the pattern of
metapopulation MHC diversity. Thus, although MHCIIβ is highly diverse and
relevant to the type and intensity of macroparasite infection in these
populations of stickleback, the main models of MHC evolution still provide
little explanatory power in this system.