Modulation of ACD6 dependent hyperimmunity by natural alleles of an Arabidopsis thaliana NLR resistance gene

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, 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 allele, indicative of genetic modifiers. Quantitative genetic analysis suggests that the population genetic basis of ACD6 modulation is complex, with different strains often carrying different large-effect modifiers. One modifier is SUPPRESSOR OF NPR1-1, CONSTITUTIVE 1 (SNC1), located in a highly polymorphic cluster of nucleotide-binding domain and leucine-rich repeat (NLR) immune receptor genes, which are prototypes for qualitative disease resistance genes. Allelic variation at SNC1 correlates with ACD6-Est activity in multiple accessions, and a common structural variant affecting the NL linker sequence can explain differences in SNC1 activity. Taken together, we find that an NLR gene can mask the activity of an ACD6 autoimmune allele in natural A. thaliana populations, thereby linking different arms of the plant immune system.Author summaryPlants defend themselves against pathogens by activating immune responses. Unfortunately, these can cause unintended collateral damage to the plant itself. Nevertheless, some wild plants have genetic variants that confer a low threshold for the activation of immunity. While these enable a plant to respond particularly quickly to pathogen attack, such variants might be potentially dangerous. We are investigating one such variant of the immune gene ACCELERATED CELL DEATH 6 (ACD6) in the plant Arabidopsis thaliana. We discovered that there are variants at other genetic loci that can mask the effects of an overly active ACD6 gene. One of these genes, SUPPRESSOR OF NPR1-1, CONSTITUTIVE 1 (SNC1), codes for a known immune receptor. The SNC1 variant that attenuates ACD6 activity is rather common in A. thaliana populations, suggesting that new combinations of the hyperactive ACD6 variant and this antagonistic SNC1 variant will often arise by natural crosses. Similarly, because the two genes are unlinked, outcrossing will often lead to the hyperactive ACD6 variants being unmasked again. We propose that allelic diversity at SNC1 contributes to the maintenance of the hyperactive ACD6 variant in natural A. thaliana populations.