Sexual development in Plasmodium: lessons from functional analyses.

Malaria is a devastating global disease with several hundred million clinical cases and just under 1 million deaths each year (http://www.who.int/topics/malaria/). It is caused by protozoan parasites of the genus Plasmodium, which have a complex life cycle in a vertebrate host and a mosquito vector. Malaria parasites are haploid throughout most of this life cycle, replicating by asexual multiplication twice in a mammalian host: in liver hepatocytes (pre-erythrocytic schizogony) and within red blood cells (blood stage schizogony), and once in the mosquito (sporogony). The essential sexual stage occurs at the transmission from vertebrate to insect. Some asexual blood stage parasites develop into either male or female gametocytes (the precursor sex cells) and following ingestion in a mosquito blood meal differentiate further into gametes in the lumen of the mosquito's gut, where fertilization takes place. The core processes of gametocytogenesis, gamete activation, exflagellation, fertilization, and zygote formation are conserved across the species from the human parasite Plasmodium falciparum to the rodent parasite Plasmodium berghei, which is an attractive laboratory model, in part because of its ease of genetic manipulation and the shorter time for the maturation and differentiation of the sexual stages. Here, we focus largely on recent functional studies using reverse genetics that have uncovered many aspects of the parasite's sexual development.