GSE68667
Epigenetic regulation of Plasmodium falciparum adaptive plasticity in the mosquito
P. falciparum undergoes antigenic variation during its life cycle in the human host. To accomplish this, the malaria parasite has developed mechanisms that ensure the expression of a single member of the var gene family to produce one of the PfEMP1 variant proteins. Here we carry out RNA-seq and ChIP-seq analyses of histone modifications to explore transcriptional and epigenomic changes taking place between the transmissible stages of the parasite i.e. gametocytes present in human blood and sporozoites present in the mosquito salivary glands. We find that most var genes are expressed at low levels in gametocytes but a single var gene is selected during the oocyst stage in the mosquito. Clonal expression of a specific var gene is accompanied by the establishment of specific histone modification patterns in the active and inactive genes. These modifications are epigenetically transmitted from the oocyst to the infective sporozoite stage, where expression of the active var gene is amplified by the transcription of an antisense lncRNA. The findings suggest a critical role for the mosquito immune system in determining the choice of var gene activation prior to transmission to the human host. Overall design: ChIP-seq and RNA-seq were performed on adult female A. gambiae midguts and salivary glands infected with P.falciparum using membrane feeding.