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

Barley <i>Mildew locus a</i> (<i>Mla</i>) 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, <i>Blumeria hordei</i> (<i>Bh</i>), to infer gene effects governed by <i>Mla6</i> and two other loci significant to disease development, <i>Blufensin1</i> (<i>Bln1</i>), and <i>Required for Mla6 resistance3</i> (<i>rar3 = Sgt1</i> _{<i>ΔKL308-309</i>} ). Interactions of <i>Mla6</i> and <i>Bln1</i> resulted in diverse epistatic effects on the <i>Bh</i>-induced barley transcriptome, differential immunity to <i>Pseudomonas syringae</i> expressing the effector protease AvrPphB, and reaction to <i>Bh</i>. 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 <i>Bh</i> 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.