How would the deciphering of the Plasmodium falciparum genome be of use to mankind?

Rehana Jauhangeer ( Dip MLT, MSc, AIBMS)

Molecular and Medical Microbiology Research Group

University of Westminster, UK.

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Introduction:

Plasmodium is a protozoan, which is the infective agent of malaria, characterised by fever and anaemia in humans. It is classified along with the coccidians Eimeria, Isospora, Cryptosporidium and Toxoplasma, and the piroplasms Babesia and Theileria in the phylum Apicomplexa, class Sporozoea (internet 1). Plasmodium infects mammals, birds and lizards, through the bite of female Anopheles (mammals), the latter acts as a vector of the infective agent. The four pathogenic species of Plasmodium to humans are: Plasmodium falciparum (P.falciparum), Plasmodium vivax, Plasmodium ovale and Plasmodium malariae. However, infection with P.falciparum leads to malaria and sometimes death.

The latest figures from the World Health Organization (WHO) indicates that there are more than 4 billion people at risk of developing malaria every year. There are about 500 million cases and 1.5-2.7 million deaths per year. About 90% of the cases of malaria that lead to death occur within the African continent (Trigg and Kondrachine, 1998).

Recently a team of US researchers and other nationals have published in Nature (2002 Vol 419 p 498-511) the complete genome sequence of Plasmodium falciparum. A genome is the total number of genes that make up an organism.(internet 1). The genes are made up of Deoxyribonucleic acid (DNA), which acts as the blueprint of the organism's cellular activities. The DNA in turn is made up of million of nucleotides, which is the four letter code. The study of the genome is called genomics. The genes then code for proteins such as enzymes and proteomics is the study of all the proteins that are encoded by the genome.

The Plasmodium falciparum genome is of 23 megabase and consists of 14 chromosomes. The latter code for 5 300 genes. The number of exons per gene is 2.39. The genome from the nucleus consists of a full set of transfer RNA (tRNA). The 43 tRNAs bind to all codons except for TGT and TGC that codes for cysteine. The 14 chromosomes vary in length and most of the variations occur in the subtelomeric regions. The 5 300 genes will code for some 5 268 predicted number of proteins. Out of these proteins, some 551 are targeted to the apicoplast. This is a structure that is homologous to chloroplasts of plants and algae and is essential for the survival of this parasite, although its exact role is not clear.

When the genome of Plasmodium falciparum is compared to other eukaryotic microbes, it is seen that it encodes for fewer enzymes and transporters. However a large proportion of its genes are used for immune evasion and host-parasite interactions. The genome of this parasite contains three gene families called var, rif and stevor.

The var genes code for proteins that are exported to the surface of red cells such that they can adhere to the epithelium of the host. The result is that infected cells remain in various organs. This then leads to the virulence of the disease and contributes to the development of severe disease. The rif genes code for rifins and the stevor genes code for stevors but their exact function have yet to be determined.

So all this fundamental information will lead to a better understanding of the parasite is a great milestone that has been achieved. Now that the scientists have the map of Plasmodium falciparum, they are now interested in the parasite's proteome. This will help to understand and learn more about its metabolism. Hopefully then, the researchers would have found the solutions to the problems that are linked to drug resistance and vaccine development.

References:

Internet 1 : http://www.els.net/els/subscriber/home/default.asp?sessionid=c83aa7fb92921621

Malcolm J. Gardner, Neil Hall, Eula Fung et al. (2002). Genome sequence of the human malaria parasite Plasmodium falciparum. Nature
419: 498 - 511.

Trigg, P.I and Kondrachine, A.V (1998). Commentary: malaria control in the 1990s.

Bull World Health Organ 1998; 76(1): 11-16.

Copyright Ó ABA

Submitted December 2002, Accepted Jan 2003

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