Histocompatibility As Adaptive Response to Discriminatory Within-organism Conflict: a Historical Model

Multicellular tissue compatibility, or histocompatibility, restricts fusion to close kin. Histocompatibility depends on hypervariable cue genes, which often have more than 100 alleles in a population. To explain the evolution of histocompatibility, I here take a historical approach. I focus on the specific example of marine invertebrate histocompatibility. I use simple game-theoretical models to show that histocompatibility can evolve through five steps. These steps include the evolution of indiscriminate fusion, the evolution of discriminatory within-organism conflict, the evolution of minor histocompatibility, the evolution of major histocompatibility, and the evolution of major histocompatibility cue polymorphism. Allowing for gradual evolution reveals discriminatory within-organism conflict as a selective pressure for histocompatibility and associated cue polymorphism. Existing data from marine invertebrates and other organisms are consistent with this hypothesis.