Genetic variation is the raw material for natural selection to act upon. Hence, there is a long history of evolutionary studies on how genetic variation is maintained in natural populations (Dobzhansky, 1982), either invoking selection or neutral processes. One of the most dramatic cases of genetic variation concerns polymorphism at Major Histocompatibility Complex (MHC) genes, which are commonly the most variable genes in vertebrate genomes (Sommer, 2005). Surprisingly, despite decades of research on MHC evolution, the evolutionary processes sustaining MHC polymorphism remain unclear, with inconsistent and often ambiguous support for competing hypotheses (Radwan et al., 2020). Here, we evaluate predictions of multiple competing MHC evolution models (adaptive and neutral),