Immune system incompatibilities between naturally occurring genomic variants underlie many hybrid defects in plants and present a barrier for crop improvement. In this review, we approach immune system incompatibilities from pan-genomic and network perspectives. Pan-genomes offer insights into how natural variation shapes the evolutionary landscape of immune system incompatibilities, and through it, selection, polymorphisms, and recombination resistance emerge as common features that synergistically drive these incompatibilities. By contextualizing incompatibilities within the immune network, immune receptor promiscuity, complex dysregulation, and single-point failure appear to be recurrent themes of immune system defects. As geneticists break genes to investigate their function, so can we investigate broken immune systems to enrich our understanding of plant immune systems and work toward improving them.
