Genetic And Phenotypic Analysis Of Clk 1 Growth Suppressors In Caenorhabditis Elegans PDF Download

"Mutations in the Caenorhabditis elegans maternal-effect gene clk-1 result in a highly pleiotropic phenotype, characterized by a general slow down in embryonic and larval development, as well as a slowing down of adult behaviors including defecation, pharyngeal pumping and swimming. First generation homozygous clk-1 mutants descended from a heterozygous mother are fully rescued for these mutant phenotypes. It has been shown that CLK-1 protein is a hydroxylase that acts in the conversion of demethoxyubiquinone (DMQ) to 5-hydroxyubiquinone, in the ubiquinone (Q) biosynthesis pathway. Consequently, clk-1 mutants accumulate the Q9 precursor, DMQ9 (the subscript refers to the length of the isoprenoid side chain). Here, I show that the profound maternal rescue observed in clk-1 maternally rescued animals is due to presence of the CLK-1 protein throughout larval development, in sufficient amounts to catalyze the production of Q9. clk-1 mutants have been shown to have a dietary requirement for Q8 due to their inability to synthesize Q9. I demonstrate that clk-1 maternally rescued animals have sufficient amounts of Q 9 to complete larval development and produce an almost full brood when raised on a Q8 deficient E. coli strain. I also show that prolonged arrest at the first larval stage, which is likely to result in degradation of any maternally contributed mRNA or protein, brings about a Clk mutant phenotype in maternally rescued animals. Finally, I reveal that the Clk mutant phenotype can be rescued at any larval stage by ectopic expression of CLK-1, suggesting that there is no developmental window for the rescue of clk-1 mutants by CLK-1. These results identify perdurance of maternally contributed product throughout development as the mechanism that accounts for the maternal effect observed in clk-1 mutants." --