Two atypical resistance proteins confer plant resistance to Melanaphis sorghi in sorghum

Aphids are among the most common insect pests that reduce crop production worldwide. However, the breeding of aphid-resistant crops is currently hindered by the scarcity of resistance genes. This problem is particularly significant in sorghum, for which resistant cultivars are urgently needed to control the aphid Melanaphis sorghi (MES). Here, we report map-based cloning of RMES1A and RMES1B, which encode two atypical resistance proteins that confer strong defense against MES. Analysis of knockout mutants and natural variations demonstrated that RMES1A and RMES1B are both required for sorghum resistance against MES. Both genes are induced by MES feeding, specifically in sclerenchyma cells and vascular bundles. RMES1A/RMES1B interact with the sorghum aphid protein MsEF1 to form a functional complex in sorghum cells, leading to key defense responses such as the H₂O₂ burst and enhanced callose deposition. Accordingly, silencing of MsEF1 expression by RNA interference disrupted RMES1A/RMES1B-mediated resistance, as evidenced by significantly greater growth and fecundity of MES aphids on a resistant cultivar. Structural modeling predicted that RMES1A/RMES1B possess a potential nucleotide-binding domain and two leucine-rich repeat domains but lack the coiled-coil or Toll/interleukin-1 receptor/resistance domains observed in typical nucleotide-binding leucine-rich repeat immune receptors (NLRs). Moreover, RMES1A/RMES1B and their homologs form a distinct cluster in a phylogenetic tree of plant NLRs and likely represent a new type of plant NLR. Our work thus reveals new resistance genes that can be used to investigate and improve immunity against insect pests in sorghum and other crops.