Figure 4

Validation of dysregulated DNA mismatch repair (MMR) pathway. (A) Divergent co-expression of pfcrt and the msh6 gene in CQR versus CQS parasites. Each dot or triangle represents the transcript level of the 2 genes in CQR and CQS parasites, respectively. The solid line is a linear fit of the data from CQR parasites and the dotted line is for data from CQS parasites. (B) Quantitative dose response variation in the response to the DNA damaging agent MMS across the Dd2 × HB3 genetic cross. (C) QTL mapping results for the MMS dose response reveals two candidate loci- chromosome 4, 60.3 cM (LOD = 2.68, chi-square P = 0.00044) and 5, 20 cM (LOD = 3.02, chi-square P = 0.000194). (D) The predicted regulon of the candidate regulator AP2 in CQR (PF3D7_0420300) is enriched with DNA repair genes including msh2 and rad51, providing further validation of MMR dysregulation. Prediction of potential targets of this AP2 was performed using an independent transcriptional data set as described in methods [68].