Genetic Interactions Between Suppressors of the Slow Defecation Phenotype of clk-1 Mutants

Many genes that are involved in nutrient and energy utilization and storage are conserved between humans and C. elegans. One of the genes involved in worm mitochondrial respiration is clk-1. This gene encodes an enzyme required for ubiquinone biosynthesis. One of the phenotypes of clk-1 mutants is altered defecation cycle: the slowing down of the defecation cycle and the inability to defecate faster at higher temperatures. these phenotypes are independent of one another. Several lines of evidence suggest that the slowed defecation of clk-1 mutants is due to alterations in lipoprotein/cholesterol metabolism because the mutant phenotype can be suppressed by the reduction of dietary cholesterol, administration of drugs affecting lipoprotein metabolism, and mutating genes involved in lipoprotein metabolism. These mutations can be separated into two classes: those which suppress the clk-1 slow defecation at 20 as well as after the shift to 25°C (class I) and those which only suppress it at 20°C (class II). Worm dsc-4 (lipoprotein assembly) and dsc-3 (metabolism of bile-like molecules) are class I suppressors. Both of these mutations restore the ability of clk-1 mutants to react to the temperature shifts. In this study we identified a novel class I suppressor pgp-2 and classified sod-4 as a class II suppressor. pgp-2 encodes a protein essential for the biosynthesis of the worm intestinal lysosome-related organelles. Mutations in both pgp-2 and sod-4 are unable to restore the ability of clk-1 worms to react to the temperature shifts. Combining different class I mutants as well as combining class I with class II mutant sod-4 revealed that the genetic interactions between class I mutants as well as genetic interactions between class I and class II mutants are hard to predict.