A new Gene Family Modulating Naturally Occuring Hyper-Immunity in Arabidopsis Identified by GWAS

Plants defend themselves against pathogens by activating an array of immune responses. Unfortunately, immunity programs may also cause unintended collateral damage to the plant itself. The quantitative disease resistance gene ACCELERATED CELL DEATH 6 (ACD6) serves as a nexus for the trade-off between growth and pathogen resistance in wild populations of Arabidopsis thaliana. An autoimmune allele, ACD6-Est-1, first identified in the natural accession Est-1, is found in over 10% of wild strains, even though it causes a clear fitness penalty under optimal growth conditions. There is, however, extensive variation in the strength of the autoimmune phenotype expressed by strains with an ACD6-Est-1 allele, indicative of genetic modifiers. Quantitative genetic analysis revealed that the population genetic basis of ACD6 modulation is rather complex, with both common and strain specific modifiers. One of these, MODULATOR OF HYPERACTIVE ACD6 1 (MHA1), codes for a small protein of ~7 kDa that has not been previously characterized. MHA1 and its paralog MHA1- LIKE (MAL) differentially interact with ACD6 proteins encoded by different ACD6 alleles, and the interactions are important for disease resistance. We propose that allelic diversity at MHA1 contributes to the maintenance of the hyperactive ACD6 variant in natural A. thaliana populations