Abstract
Nutrient acquisition/metabolism pathways provide potent targets for drug design. We conducted crosses between African (NF54) and Asian (NHP4026) malaria parasites, and compared genome-wide allele frequency changes in independent progeny populations grown in human serum or AlbuMAX, a commercial bovine serum formulation. We detected three QTLs linked with differential growth that contained strong candidate genes: aspartate transaminase AST (chromosome 2), cysteine protease ATG4 (chr. 13) and EBA-140 (chr. 14). Alleles inherited from NF54 (chr. 2 and 14) and from NHP4026 (chr. 13) were positively selected in AlbuMAX, while the same alleles were selected against in serum. Selection driving differential growth was strong (s = 0.10 – 0.23 per 48-hour lifecycle) and observed in all biological replicates. These results demonstrate the effectiveness of bulk segregant approaches for revealing nutritional polymorphisms in Plasmodium falciparum. This approach will allow systematic dissection of nutrient acquisition/metabolism pathways that are potential targets for intervention against P. falciparum.
Competing Interest Statement
The authors have declared no competing interest.