Fig 1.
Praziquantel affects C. elegans development.
Dose response for the N2 (orange) and JU775 (purple) strains in praziquantel (PZQ), (S)-PZQ, and (R)-PZQ. The y-axis represents development measured as median optical density normalized for animal length. Linetype indicates the type of drug: solid = PZQ racemate, long dash = (S)-PZQ, and short dash = (R)-PZQ.
Fig 2.
A) Genome-wide association mapping results for median normalized optical density (median.norm.EXT) across 74 wild strains. The genomic position (x-axis) is plotted against the -log10(p) value (y-axis) for each SNV. Legend: dots: SNV, red dot: SNV passes the genome-wide Bonferroni significance threshold designated by the gray line. B) At the SNV with the highest -log10(p) value (position 1,169,239), genotypes are split based on the presence of the reference allele (REF) or the alternative allele (ALT). The y-axis shows development measured as median optical density normalized for animal length (median.norm.EXT) with each point representing the average median.norm.EXT response of a single wild strain. The N2 strain is shown in orange, and the JU775 strain is shown in purple. These strains are also indicated with a corresponding arrowhead. C) Fine mapping of variants in the QTL on chromosome IV. The genomic position is shown on the x-axis, and the -log10(p) values for variants are shown on the y-axis. Genes within the region are shown as rectangles and colored by the strand (turquoise = + strand, purple = —strand). Variants (amino acid changes) with a predicted moderate impact on gene function are shown in orange, and variants with a predicted high impact on gene function (frame-shift, stop-gain, start-loss) are shown in red. The gene cct-8 is labeled on the plot directly left of the corresponding rectangle for the gene.
Fig 3.
A) Expression of cct-8, hsp-16.2, and hsp-70 in control conditions (black) and PZQ (gray) in the strains N2 and JU775. The biological samples were spread over two 96-well plates per gene (triangles and circles). B) Expression of hsp-16.2 and hsp-70 after treatment with RNAi or praziquantel (PZQ) in the strain N2. *, **, and *** indicate p-values of less than 0.05, 0.01, and 0.001, respectively.
Fig 4.
A) The gene model for the longest isoform of cct-8 is shown. Exons are shown in dark gray and introns as lines connecting the exons. The variant G226V is shown on the exon where it is located. B) The amino acid sequences of the N2 and JU775 versions of CCT-8 are shown aligned around the region containing the G226V variant. Figure made with ggmsa [44] C) Animal development measurements. Median optical density normalized for animal length (median.norm.EXT) in 1 mM praziquantel is shown on the y-axis. The x-axis shows the strains tested: N2, ECA485 (N2 background with the JU775 allele in cct-8), JU775, and ECA601 (JU775 background with N2 allele in cct-8). Each point represents the median.norm.EXT for a population of animals in the presence of praziquantel normalized for their response in 1% DMSO. ns = not significant.