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20 reviewsCommon wheat and durum wheat are widely cultivated cereal crops, both ofwhich are infected by the obligate biotrophic pathogen Blumeria graminis f.sp. tritici (Bgt), causing powdery mildew. Recently, Pm68 gene was identifiedon the short arm of chromosome 2B in the Greek durum wheat line TRI 1796,conferring resistance to this disease. Here, we have cloned Pm68 from TRI 1796using an integrated approach of genetic mapping, association analysis andPacBio sequencing. Transgenic assays demonstrate that Pm68 mediatedresistance is controlled by a pair of genetically linked nucleotide-bindingleucine-rich repeat (NLR)-encoding genes, Pm68-1 and Pm68-2. Transientexpression assays in Nicotiana benthamiana leaves reveal that the activation ofPm68-1 is positively modulated by Pm68-2, likely through its N-terminal coiledcoil (CC)-like domain. Evolutionary analysis traces the origin of Pm68 to aspecific wild emmer subpopulation. The introgression and transgenic wheatlines carrying this gene show no significant negative effects on major agronomic traits, highlighting the potential value of Pm68 for disease-resistantbreeding programs of both durum wheat and common wheat.