Learning new biology from the study of natural variation

For many years, it was unclear how the transmembrane protein ACD6 contributes to immunity in the plant Arabidopsis thaliana. By studying natural genetic variation, we discovered two small proteins that bind to ACD6, with one positively regulating the standard version of ACD6 and the other negatively regulating a naturally hyperactive version of ACD6. These insights in turn spurned experiments that revealed ACD6 to be an ion channel. Together, these experiments highlight how the study of genetic variation can reveal new biology that is not accessible to standard genetic screens.