Ancient pangenomic origins of noncanonical NLR genes underlying the recent evolutionary rescue of a staple crop

Evolutionary rescue occurs when populations in deteriorating environments avoid extinction by rapid adaptation. The recent evolutionary rescue of the cereal crop sorghum via RMES1 aphid resistance is among a few known in situ cases, but its pangenomic origins and molecular basis is not yet known. Here, we describe the behavioral effects, molecular endophenotypes, and pangenomic evolution underlying this evolutionary rescue. Analysis of near-isogenic lines show that RMES1 disrupts phloem feeding via global immunity activation of conserved defense networks. A growth-to-defense transition is evidenced by extensive transcriptome remodeling (>15% of expressed genes) and mediated by salicylic acid signaling. Nucleotide-binding leucine-rich repeat (NLR) immune receptor genes at the RMES1 locus harbored on a large tandem duplication have extensive copy number variation across the sorghum pangenome. The likely causative NLRs (RMES1A and RMES1B) were inferred from expression and structural variation. The NLRs encoded at RMES1 lack an N-terminal signaling domain and have nucleotide-binding domain sequence variation expected to result in a loss of ATP binding, suggesting RMES1 NLRs function via a noncanonical mechanism. The RMES1 NLR family is shared across the grass super-pangenome and includes the brown planthopper resistance gene BPH40 in Oryza sativa, which is syntenic to RMES1. Finally, k-mer analysis of RMES1 haplotypes in the sorghum pangenome established the East African origin of rare standing variation for resistance. Thus, the birth-and-death process at an ancient gene cluster generated pangenomic variation that was recruited to activate coordinated defense pathways and provide evolutionary rescue.