Fig. 3: Naturally occurring variants in PfACS10 can confer resistance to MMV665924.

EC₅₀ a Pairwise nucleotide diversity (π) and divergence (F_ST) between Malawian and Senegalese populations for 4614 genes in P. falciparum. Members of the ACS family are indicated in red. The 95th percentile is indicated by a dotted line. Overall, pairwise π of Malawi and Senegal is highly correlated (two-tailed Pearson R² = 0.94, p < 1 × 10⁻¹⁵) and generally relatively low (median of 0.0003207 and 0.0003214 for Senegal and Malawi, respectively). b Distribution of non-synonymous single nucleotide polymorphism with global MAF > 0.01 from globally diverse isolates (www.malariagen.net/pf3k). The length of the bars represents the local MAF of each variant in West (blue) or East (purple) Africa. The selected variants are indicated by red, blue, and yellow arrows. Dark green boxes indicate the ACS motifs: P: P-loop, G: Gate motif, A: Adenine binding site, L: Linker. c Representative dose-response assay for a clonal line of CF04.008 (ACS10 M300, gray) and two clonal lines of CF04.009 (ACS10 M300I, red) from Malawi. Assays were run in triplicate and repeated twice. Shown are the average ±SD and the non-linear regression curve fit for one biological assay run in triplicate. Source data are provided as a Source Data file. MAF minor allele frequency, π pairwise nucleotide diversity within each country, F_ST divergence.