Figure 1

AS lineage of drug resistant P. chabaudi parasite clones. The cloned isolate AS-sens is sensitive to pyrimethamine (PYR), chloroquine (CQ), mefloquine (MF), artemisinin (ART) and artesunate. After passage in mice in the presence of PYR (single dose) and subsequently after multiple passage with increasing sub-lethal doses of CQ, MF, ART or artesunate (blue), surviving parasites were cloned to give AS-PYR1, AS-3CQ, AS-30CQ, AS-15MF, AS-ATN and AS-ART [13–16, 49]. AS-15MF, AS-30CQ and AS-ATN were derived from an uncloned line, AS-15CQ [14]. ^♣ Two genetic backcrosses, between the genetically distinct drug-sensitive clone AJ and two members of the AS lineage (AS-15MF, AS-30CQ), were subjected to Linkage Group Selection (LGS) analysis. ^† Clones AS-sens, AS-30CQ and AS-15MF were subjected to whole-genome re-sequencing. Two specific gene mutations (red) that underlie PYR or ART resistance are shown at positions that indicate their origin within the lineage. Specific amino-acid substitutions refer to gene predictions in P. chabaudi. The predicted relationship between AS-sens and AS-WTSI is indicated as co-descendants of the ancestral AS isolate.