The RC strain is highly diverged and harbors putatively novel drug resistance variants.

Background: The current first line drugs for treating uncomplicated malaria are artemisinin (ART) combination therapies. However, parasites resistant to ART and partner drugs are spreading, which threatens malaria control efforts. Rodent malaria species are useful models for understanding antimalarial resistance, in particular genetic variants responsible for cross resistance to different compounds.

Methods: The RC strain (RC) is described as resistant to different antimalarials, including chloroquine (CQ) and ART. In an attempt to identify the genetic basis for the antimalarial resistance trait in RC, its genome was sequenced and compared with five other previously sequenced strains.

Results: We found that RC is eight-fold less sensitive to the ART derivative artesunate than the reference strain ANKA. The genome of RC is markedly different from other strains, and 6,974 single nucleotide variants private to RC were identified. Among these RC private variants, non-synonymous changes were identified in genes known to modulate antimalarial sensitivity in rodent malaria species, including notably the ubiquitin carboxyl-terminal hydrolase 1 gene. However, no variants were found in some genes with strong evidence of association with ART resistance in such as K13 propeller protein.

Discussion: The variants identified in RC provide insight into genome diversity and genetic factors that could modulate CQ and ART resistance in spp.