Kj. Dechering et al., Isolation and functional characterization of two distinct sexual-stage-specific promoters of the human malaria parasite Plasmodium falciparum, MOL CELL B, 19(2), 1999, pp. 967-978
Transmission of malaria depends on the successful development of the sexual
stages of the parasite within the midgut of the mosquito vector. The diffe
rentiation process leading to the production of the sexual stages is deline
ated by several developmental switches. Arresting the progression through t
his sexual differentiation pathway would effectively block the spread of th
e disease. The successful development of such transmission-blocking agents
is hampered by the lack of a detailed understanding of the program of gene
expression that governs sexual differentiation of the parasite. Here we des
cribe the isolation and functional characterization of the Plasmodium falci
parum pfs16 and pfs25 promoters, whose activation marks the developmental s
witches executed during the sexual differentiation process. We have studied
the differential activation of the pfs16 and pfs25 promoters during intrae
rythrocytic development by transfection of P. falciparum and during gametog
enesis and early sporogonic development by transfection of the related mala
rial parasite P. gallinaceum. Our data indicate that the promoter of the pf
s16 gene is activated at the onset of gametocytogenesis, while the activity
of the pfs25 promoter is induced following the transition to the mosquito
vector. Both promoters have unusual DNA compositions and are extremely A/T
rich. We have identified the regions in the pfs16 and pfs25 promoters that
are essential for high transcriptional activity. Furthermore, we have ident
ified a DNA-binding protein, termed PAF-1, which activates pfs25 transcript
ion in the mosquito midgut. The data presented here shed the first light on
the details of processes of gene regulation in the important human pathoge
n P. falciparum.