Evolution of HMA-integrated tandem kinases accompanied by expansion of target pathogens

Tandem kinase proteins (TKPs) are an emerging family of plant intracellular immune receptors that offer potential for developing novel disease resistance. We cloned Rmo2 and Rwt7, genes for resistance to the blast fungus, from barley and wheat, respectively, and discovered that they are orthologs encoding TKPs with an integrated N-terminal heavy metal-associated (HMA) domain. Rmo2 was collocated with Rpg1, a TKP gene for resistance to stem rust, while Rwt7 was collocated with WTK4, a TKP gene for resistance to powdery mildew. Domain swapping suggested that the HMA domain determines target effector specificity of these genes. We propose a model illustrating an evolutionary process in which a TKP gene has differentiated into paralogs and orthologs that recognize various effectors through diversification of their HMA domains.