RT Journal Article SR Electronic T1 Antagonistic paralogs control a switch between growth and pathogen resistance in C. elegans JF bioRxiv FD Cold Spring Harbor Laboratory SP 357756 DO 10.1101/357756 A1 Kirthi C. Reddy A1 Tal Dror A1 Ryan S. Underwood A1 Guled A. Osman A1 Christopher A. Desjardins A1 Christina A. Cuomo A1 Michalis Barkoulas A1 Emily R. Troemel YR 2018 UL http://biorxiv.org/content/early/2018/06/28/357756.1.abstract AB Immune genes are under intense pressure from pathogens, which cause these genes to diversify over evolutionary time and become species-specific. Through a forward genetic screen we recently described a C. elegans-specific gene called pals-22 to be a repressor of “Intracellular Pathogen Response” or IPR genes. Here we describe pals-25, which, like pals-22, is a species-specific gene of unknown biochemical function. We identified pals-25 in a screen for suppression of pals-22 mutant phenotypes and found that mutations in pals-25 suppress all known phenotypes caused by mutations in pals-22. These phenotypes include increased IPR gene expression, thermotolerance, and immunity against natural pathogens. Mutations in pals-25 also reverse the reduced lifespan and slowed growth of pals-22 mutants. Transcriptome analysis indicates that pals-22 and pals-25 control expression of genes induced not only by natural pathogens of the intestine, but also by natural pathogens of the epidermis. Indeed, in an independent forward genetic screen we identified pals-22 as a repressor and pals-25 as an activator of epidermal defense gene expression. These phenotypic and evolutionary features of pals-22 and pals-25 are strikingly similar to species-specific R gene pairs in plants that control immunity against co-evolved pathogens.