Figure 3. The P. falciparum dihydrofolate reductase (PfDHFR) isolate data was grouped into seven geographical areas: South America, West Africa, Middle Africa, Eastern Africa, Southern Asia, Southeastern Asia, and Melanesia.

The bar charts display the frequency (log scale) of the combinations of the four mutations N51I, C59R, S108N, and I164L. The frequency data has been multiplied by a factor of 10 to enable clear identification of those mutations occurring in one isolate only. The most likely evolutionary trajectory inferred from the frequency of combinations are included above the corresponding frequency chart from which the pathways were inferred indicated by mutations separated by dark red arrows. Alternative pathways are indicated by mutations separated by light red arrows. Where only single mutations are present a pathway is not inferred. (See Supplementary data folder ‘PfDHFR/IsolateMutationFrequency’ for the frequency of all mutations found in the isolate data from these regions.)