cell, the parasite progresses through several morphologically distinguishable stages, called the ring stage, the trophozoite, and the schizont. The schizont-infected red blood cells eventually burst, releasing up to 16 new merozoites into the blood stream that infect new red blood cells and continue the cycle. P. knowlesi completes this red blood cell cycle every 24 hours, making it uniquely rapid among primate-infecting Plasmodium species (which generally take 48 or 72 hours). Occasionally, parasites that invade red blood cells instead enter a sexual cycle, developing over approximately 48 hours into distinct sexual forms called microgametocytes or macrogametocytes. These gametocytes remain in the blood to be ingested by mosquitoes. A mosquito ingests gametocytes when it takes a blood meal from an infected primate host. Once inside the mosquito gut, the gametocytes develop into gametes and then fuse to form a diploid zygote. The zygote matures into an ookinete, which migrates through the wall of the mosquito gut and develops into an oocyst. The oocyst then releases thousands of sporozoites, which migrate through the mosquito to the salivary glands. This entire process in the mosquito takes 12 to 15 days. Cell biology P. knowlesi largely resembles other Plasmodium species in its cell biology. Its genome consists of 23.5 megabases of DNA separated into 14 chromosomes. It contains approximately 5200 protein-coding genes, 80% of which have orthologs present in P. falciparum and P. vivax. The genome contains two large gene families that are unique to P. knowlesi: the SICAvar (schizont-infected cell agglutination variant) family, which is involved in displaying different antigens on the parasite surface to evade the immune system, and the Kir (knowlesi interspersed repeat) family, involved in adhering parasitized red blood cells to blood vessel walls. As an apicomplexan, P. knowlesi has several distinctive structures at its apical end that are specialized for invading host cells. These include the large bulbous rhoptries, smaller micronemes, and dispersed dense granules, each of which secretes effectors to enter and modify the host cell. Like other apicomplexans, P. knowlesi also has two organelles of endosymbiotic origin: a single large mitochondrion and the apicoplast, both of which are involved in the parasite's metabolism. Evolution and taxonomy Despite its morphological similarity to P. malariae, P. knowlesi is most closely related to P. vivax as well as other Plasmodium species that infect non-human primates. The last common ancestor of all modern P. knowlesi strains lived an estimated 98,000 to