A Species-wide Analysis of Genetic Incompatibilities Identifies NLR Loci as Hotspots of Deleterious Epistasis

Intraspecific genetic incompatibilities can reduce gene flow and thereby influence genome- and species-wide patterns of sequence variation. A common incompatibility in plants is hybrid necrosis, characterized by autoimmune responses in F1 or F2 progeny due to epistatic interactions between natural genetic variants. By systematically testing thousands of F1 hybrids of Arabidopsis thaliana strains, we identified a small number of incompatibility “hotspots” in the genome, which often lie in regions densely populated by NLR immune receptor genes. In several cases, these immune receptor loci interact with each other, suggestive of intragenomic conflict within the immune system. A particularly dangerous locus is a highly variable cluster of NLR genes, DANGEROUS MIX2 (DM2), which causes multiple, independent incompatibilities with other genes that encode a range of biochemical functions. Our findings suggest that the prevalence of antagonistic interactions among immune receptors and other proteins limit the accessible genotypic space during evolution of plant species.