Comparative transcriptomics reveal differential gene expression in geographical isolates and implications on erythrocyte invasion mechanisms.

uses Duffy binding protein (PvDBP1) to bind to the Duffy Antigen-Chemokine Receptor (DARC) to invade human erythrocytes. Individuals who lack DARC expression (Duffy-negative) are thought to be resistance to . In recent years, malaria is becoming more prevalent in Africa with a portion of these cases detected in Duffy-negatives. Apart from DBP1, members of the reticulocyte binding protein (RBP) and tryptophan-rich antigen (TRAg) families may also play a role in erythrocyte invasion. While the transcriptomes of the Southeast Asian and South American are well documented, the gene expression profile of in Africa and more specifically the expression level of several erythrocyte binding gene candidates as compared to DBP1 are largely unknown. This paper characterized the first transcriptome in Africa and compared with those from the Southeast Asian and South American isolates. The expression of 4,404 gene transcripts belong to 12 functional groups including 43 specific erythrocyte binding gene candidates were examined. Overall, there were 10-26% differences in the gene expression profile amongst the geographical isolates, with the Ethiopian and Cambodian being most similar. Majority of the gene transcripts involved in protein transportation, housekeeping, and host interaction were highly transcribed in the Ethiopian . Erythrocyte binding genes including 2a and 3 expressed six-fold higher than 1and 60-fold higher than P/2. Other genes including , , and also showed relatively high expression. Differential expression was observed among geographical isolates, e.g., 1 and P/2 were highly expressed in the Cambodian but not the Brazilian and Ethiopian isolates, whereas 2a and 2b showed higher expression in the Ethiopian and Cambodian than the Brazilian isolates. Compared to 25, the standard biomarker for detecting female gametocytes, (PVP01_1440800), GAP (PVP01_1403000), and (PVP01_1208000) were highly expressed across geographical samples. These findings provide an important baseline for future comparisons of transcriptomes from Duffy-negative infections and highlight potential biomarkers for improved gametocyte detection.