Eukaryotes Genomes - PLASMODIUM FALCIPARUM

Plasmodium falciparum causes human malaria and despite more than a century of efforts to eradicate or control malaria, the disease remains a major and growing threat to the public health and economic development of countries in the tropical and subtropical regions of the world. Approximately 40% of the world's population lives in areas where malaria is transmitted. There are an estimated 300-500 million cases and up to 2.7 million deaths from malaria each year. The mortality levels are greatest in sub-Saharan Africa, where children under 5years of age account for 90% of all deaths due to malaria.

Human malaria is caused by infection with intracellular parasites of the genus Plasmodium that are transmitted by Anopheles mosquitoes. Of the four species of Plasmodium that infect humans, Plasmodium falciparum is the most lethal. Resistance to anti-malarial drugs and insecticides, the decay of public health infrastructure, population movements, political unrest, and environmental changes are contributing to the spread of malaria.

P. falciparum infection in humans begins when an infected Anopheles sp. mosquito takes a blood meal and injects infective sporozoites into the peripheral circulation of its vicitm. Within minutes, these sporozoites invade hepatocytes in the liver and, over approximately one week, undergo asexual multiplication, producing tens of thousands of merozoite forms of the parasite. When the infected hepatocyte ruptures, merozoites are released into the peripheral circulation. The merozoites then invade red blood cells and complete another round of multiplication within 48-72 hours, with the production of 16-20 additional merozoites per red blood cell, which devour the haemoglobin in the process. The released merozoites invade additional red blood cells and carry on the cycle. It is the synchronous release of merozoites that is thought to be responsible for the periodic fevers associated with malaria.

Some invading merozoites do not divide, but differentiate into male (microgametocyte) and female (macrogametocyte) sexual forms. These sexual forms are taken from the bloodstream by a feeding Anopheles sp. mosquito and fertilise in the mosquito midgut to form zygotes. These zygotes further differentiate into motile forms, called ookinetes, migrate through the mosquito gut wall and divide within oocysts on the external gut wall to form thousands of sporozoites. The infective sporozoites are released into the mosquito haemocoele and move to the salivary gland, where they await injection into another human host, thus completing the life cycle.

Resistance is one of the big obstacles to controlling malaria. In Africa, the parasite's resistance to the inexpensive and commonly used drug chloroquine is widespread. Meanwhile, the mosquito's resistance to DDT and other insecticides has grown, making some insecticide-coated nets useless. Currently, no effective vaccines exist. The malaria parasite is a crafty pathogen; it can change proteins on the surfaces of its cells to evade detection by the human immune system. As soon as the immune system begins to recognize and attack the parasite, it switches its surface armor of proteins.

An international effort was launched in 1996 to sequence the P. falciparum genome with the expectation that the genome sequence would open new avenues for research. The elucidation of the genome of the malaria parasite will provide researchers with a powerful tool for dissecting the biology of this complex organism, and may speed the discovery of a desperately needed treatment for malaria.

Plasmodium falciparum, has a genome size of c. 23 MB, composed of 14 chromosomes. They range in size between 0.7 - 3.3 MB, and are numbered in order of ascending size. There are estimated to be around 5300 genes in the genome. The first draft of the genome was published in October 2002.

References:

Nature 419 (6906):527-531 (2002)
Nature 400 (6744):532-538 (1999)
http://www.sanger.ac.uk/Projects/P_falciparum/
http://www-ermm.cbcu.cam.ac.uk/dcn/fig001dcn.htm
http://www.nature.com/genomics/papers/p_falciparum.html
http://www.genomenewsnetwork.org/articles/10_02/parasite_mosquito.shtml