Abstract
Immune genes are under intense, pathogen-induced pressure, which causes 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, including Nematocida parisii microsporidia and the Orsay virus. 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. In summary, the species-specific pals-22 and pals-25 genes act as a switch to regulate a program of gene expression, growth, and defense against diverse natural pathogens in C. elegans.
Highlights
Ancient genes control core processes in diverse organisms
In this work we describe a pair of species-specific genes called pals-22/pals-25 that promote resistance against natural pathogens of the small roundworm Caenorhabditis elegans
We show that mutations in pals-25 strongly suppress all the physiological phenotypes seen in pals-22 mutants, including IPR gene expression, stress resistance, lifespan, development and transgene silencing
Summary
Ancient genes control core processes in diverse organisms. For example, the >500 million-year-old Hox gene cluster is required for establishing body plan polarity in animals as diverse as worms, flies and humans [1]. Pathogen infection imposes some of the strongest selective pressure on organisms, and many species-specific, expanded gene families are involved in immunity. One example is the family of mouse Naip genes, which encode sensor proteins in the inflammasome that detect bacteria to trigger cytokine release and cell death [4]. Another example is the plant R genes, which detect virulence factors from co-evolved pathogens to activate effectortriggered immunity [5]. A growing theme in plant R genes is that they can function as opposing gene pairs, with one R gene promoting host defense and the other R gene inhibiting host defense Of note, both the Naip and R genes were identified through unbiased forward genetic screens for immune genes
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