Researchers have known since the late nineteenth century that malaria is caused by four different, closely related parasites. One of these, Plasmodium falciparum, is the most deadly, and therefore the focus of intense research. However, no effective malaria vaccine has ever been found, and the parasite is rapidly developing resistance to known anti-malarial drugs. Gaining a better understanding of the inner workings of the parasite could be crucial for making progress in new drug and vaccine development.

The Malaria Genome Sequencing Consortium was established to sequence the entire genome of P. falciparum. Now S. Bowman from the Sanger Centre, Hinxton, UK and colleagues have finished sequencing chromosome 3 of the parasite. As reported in Nature [5 August 1999]":http://toc-prod.edoc.com/server-java/Propub/nature/400532A0.abs_frameset, the sequence has over a million bases of nucleic acid - the building blocks of DNA - and contains 215 protein-encoding genes.

To sequence the chromosome, Bowman's group used what is called a 'whole-sequence shotgun,' meaning that they shredded the chromosome up into small pieces that were sequenced separately and then put back into order, like the pieces of a puzzle. This turned out to be quite difficult because the parasite's chromosome has a lot of repeated parts, making it hard to figure out the order of the small pieces. But the final result is a sequence of DNA that is as long as the entire genome of a bacterium.

Chromosome 2 of P. falciparum has already been sequenced. Having the sequences of the two different chromosomes allows crucial comparisons to be made, giving researchers insight into the way genes are organized and how they function in the malaria parasite. For instance, they found that there is a lot of gene 'clustering'- many of the genes that code for proteins needed at a specific part of the parasite's life-cycle are grouped together on the chromosome. One theory is that, because the genes are grouped together, they might be regulated as a unit and all turned on by the same signal. However, this is still speculation.

Bowman's group may have identified the DNA that is known as the centromere. As its name suggests, it is located at the centre of the chromosome, and is crucial for separating a chromosome from its twin copy during cell division. The group also found that near the ends of the chromosomes - the telomeres - are very specific features, such as repetitive DNA sequences and many genes that are needed by the organism to cause malaria in humans.

Finally, a surprising finding was that many of the genes are spliced. In other words, there are regions of DNA within some of the parasite's genes that are cut out and not included in the sequences used to make proteins. This splicing is quite common in many organisms, including humans, but was thought to be extremely rare in P. falciparum.

"Now that we have a part of the genome sequence to hand, it is imperative that we use it to identify new drug targets, to understand the pathogenesis of malaria and to help in constructing vaccines," comment Mats Wahlgren and Maria Teresa Bejarano of the Karolinska Institute and the Swedish Institute for Infectious Disease Control, Stockholm.