Diverse epistatic effects in barley-powdery mildew interactions localize to host chromosome hotspots

Barley Mildew locus a (Mla) encodes a multi-allelic series of nucleotide-binding leucine-rich repeat (NLR) receptors that specify recognition to diverse cereal diseases. We exploited time-course transcriptome dynamics of barley and derived immune mutants infected with the powdery mildew fungus, Blumeria hordei (Bh), to infer gene effects governed by Mla6 and two other loci significant to disease development, Blufensin1 (Bln1), and Required for Mla6 resistance3 (rar3 = Sgt1 ). Interactions of Mla6 and Bln1 resulted in diverse epistatic effects on the Bh-induced barley transcriptome, differential immunity to Pseudomonas syringae expressing the effector protease AvrPphB, and reaction to Bh. From a total of 468 barley NLRs, 115 were grouped under different gene effect models; genes classified under these models localized to host chromosome hotspots. The corresponding Bh infection transcriptome was classified into nine co-expressed modules, linking differential expression with pathogen structures, signifying that disease is regulated by an inter-organismal network that diversifies the response.