Photograph © SPL

Knowing thy enemy puts you in a stronger position to defeat it. This tactic is no more true in life than in combatting widespread and potentially deadly infections, such as those caused by the malaria parasite Plasmodium falciparum, which kills ∼2.7 million people each year (see figure). Efforts to curb P. falciparum have met with relative success — but ultimately the effectivess of any drug or vaccine will depend largely on how old, and therefore how variable, this parasite really is. If, as some believe, the parasite suffered a severe bottleneck 3,000–5,000 years ago, then the existing parasite isolates would be too genetically homogeneous to develop resistance to drugs that are directed against it. Appealing though it might be, this view, which is known as the Malaria's Eve hypothesis, is also very controversial. Now, two investigations, both led by Xin-zhuan Su, knock back this idea through an analysis of the largest ever genome sampling of P. falciparum. The genetic diversity of P. falciparum suggests that this parasite could be as much as 180,000 years old, and that, as feared, it rapidly develops resistance to anti-malarial drugs.

Different studies on the age of P. falciparum have given wildly different estimates. To settle the matter, Jianbing Mu and colleagues examined isolates from five divergent parasite clones for variation in SNPs and microsatellites in the coding and non-coding regions of 204 genes, all on chromosome 3. The markers were valuable for constructing a molecular map of this chromosome, which can be used for future gene-mapping studies. More importantly for the issue at hand, however, was the level of genetic change observed in neutrally evolving sequences. There was no evidence of a severe recent bottleneck in the parasite's genetic history. Instead, the analysis revealed that the P. falciparum population is very ancient and diverse, and that it could have been present when humans first started migrating around the globe. The malaria parasite could therefore be as diverse as we are — and so pose a threat to existing vaccination strategies.

What does this mean for the parasite's ability to resist drugs? The results of the second study are rather disheartening. Wootton et al. analysed the variation in and around the pfcrt gene, which confers resistance to chloroquine, a common anti-malarial drug. The level of diversity in and around this gene — measured by genotyping microsatellite markers in 87 isolates — was noticeably higher in drug-sensitive than in drug-resistant strains, showing that the selective pressure of using drugs can decrease variability at specific loci. The authors further show that, instead of there being only two independently evolved chloroquine-resistant alleles, there are four, and that they are spreading quickly through the population.

It's unlikely that, on the basis of this work alone, malarial researchers will reach a consensus on the true age and genetic diversity of P. falciparum, and on the impact of this knowledge on public health measures. However, in an accompanying News and Views, Andrew Clark is optimistic that, through more thorough genetic monitoring and by creating common P. falciparum collections and databases, agreement shouldn't be too far off.