Every day, at least 2,700 children die from an infection by the human malarial parasite Plasmodium falciparum. Almost all of these cases are in sub-Saharan Africa, where, if the children live through their earliest infections, they might go on to fight up to 40 separate malarial infections in their lifetime. Malaria is the third leading killer of humans, and increasing resistance of the parasite to current drugs is alarming. Many scientists have devoted their lifetimes to combating this scourge, and they've just been handed their enemy's battle plan: its genome.

After six years of difficult sequencing and assembly, the Malaria Genome Project published the mostly complete sequences of two species of PlasmodiumP. falciparum, the human parasite, and P. y. yoelii, a rodent parasite — in the October 3 issue of Nature. The extremely high A+T content, more than 80%, of both these 23-Mb genomes was often arranged in runs of 50 As or Ts, embodying a genome assembler's worst nightmare. A partial solution, also used for other (A+T)-rich genomes, was to separate most of the 14 chromosomes and sequence each separately.

Of course, of most interest are potential drug or vaccine targets. About 5,300 genes were identified in P. falciparum, and 60% of those showed no significant similarity to previously known proteins. Of particular therapeutic interest are the 10% of all proteins targeted to the apicoplast, a parasite-specific subcellular compartment that is essential for its survival but of unknown function. Gardner et al. suggest that several apicoplast metabolic pathways, such as isopentyl diphosphate biosynthesis, should be investigated further for antimalarials. The need for developing new therapeutics is urgent, as all current treatments were developed between 50 and 4,000 years ago.

Florens et al. and Lasonder et al. looked at proteins expressed at different stages of the parasite's life cycle, a task made more intriguing by the fact that over half of the proteins were hypothetical. They focused on novel cell-surface proteins and secreted proteins, which, if parasite specific, would make excellent drug or vaccine targets.

Of course, the bonus to malaria researchers is doubled with the sequence of the insect vector Anopheles gambiae (see Highlight below). Combined with the human genome, we now have the blueprints for all members of this deadly play. Thus, in one historic week, we've entered the post-genomic period in malaria research, full of challenges but with incredible promise for future preventative measures.