Introductory paragraph
Crop diseases reduce wheat yields by ~25% globally and thus pose a major threat to global food security1. Genetic resistance can reduce crop losses in the field and can be selected for through the use of molecular markers. However, genetic resistance often breaks down following changes in pathogen virulence, as experienced with the wheat yellow (stripe) rust fungus Puccinia striiformis f. sp. tritici (PST)2. This highlights the need to (i) identify genes that alone or in combination provide broad-spectrum resistance and (ii) increase our understanding of the underlying molecular mode of action. Here we report the isolation and characterisation of three major yellow rust resistance genes (Yr7, Yr5, and YrSP) from hexaploid wheat (Triticum aestivum), each having a distinct and unique recognition specificity. We show that Yr5, which remains effective to a broad range of PST isolates worldwide, is allelic to YrSP and paralogous to Yr7, both of which have been overcome by multiple PST isolates. All three Yr genes belong to a complex resistance gene cluster on chromosome 2B encoding nucleotide-binding and leucine-rich repeat proteins (NLRs) with a non-canonical N-terminal zinc-finger BED domain3 that is distinct from those found in non-NLR wheat proteins. We developed and tested diagnostic markers to accelerate haplotype analysis and for marker-assisted selection to enable the stacking of the non-allelic Yr genes. Our results provide evidence that the BED-NLR gene architecture can provide effective field-based resistance to important fungal diseases such as wheat yellow rust.