Bulk Segregant Approaches to Nutritional Genomics in Plasmodium falciparum
Kumar S., Li X., McDew-White M., Reyes A., Sayeed A., Haile MT., Kennedy SY., Camargo N., Checkley LA., Vendrely KM., Button-Simons KA., Cheeseman IH., Kappe SH., Nosten F., Ferdig MT., Vaughan AM., Anderson TJC.
<jats:title>Abstract</jats:title><jats:p>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 <jats:italic>AST (chromosome 2), cysteine protease ATG4 (chr. 13)</jats:italic> and <jats:italic>EBA-140 (chr. 14)</jats:italic>. 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 (<jats:italic>s</jats:italic> = 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 <jats:italic>Plasmodium falciparum</jats:italic>. This approach will allow systematic dissection of nutrient acquisition/metabolism pathways that are potential targets for intervention against <jats:italic>P. falciparum</jats:italic>.</jats:p>