The evolutionary landscape of antifolate resistance in Plasmodium falciparum.

Resistance to antifolates in Plasmodium falciparum is well described and has been observed in clinical settings for decades. At the molecular level, point mutations in the dhfr gene that lead to resistance have been identified, and the crystal structure of the wildtype and mutant dihydrofolate reductase enzymes have been solved in complex with native substrate and drugs. However, we are only beginning to understand the complexities of the evolutionary pressures that lead to the evolution of drug resistance in this system.

Fitness trade-offs in the evolution of dihydrofolate reductase and drug resistance in Plasmodium falciparum.

Background: Patterns of emerging drug resistance reflect the underlying adaptive landscapes for specific drugs. In Plasmodium falciparum, the parasite that causes the most serious form of malaria, antifolate drugs inhibit the function of essential enzymes in the folate pathway. However, a handful of mutations in the gene coding for one such enzyme, dihydrofolate reductase, confer drug resistance.

Compensatory mutations restore fitness during the evolution of dihydrofolate reductase.

Whether a trade-off exists between robustness and evolvability is an important issue for protein evolution. Although traditional viewpoints have assumed that existing functions must be compromised by the evolution of novel activities, recent research has suggested that existing phenotypes can be robust to the evolution of novel protein functions. Enzymes that are targets of antibiotics that are competitive inhibitors must evolve decreased drug affinity while maintaining their function and sustaining growth.

Spatial learning and memory in African mole-rats: the role of sociality and sex.

Spatial learning and memory is an important skill for the survival and fitness and may vary between the sexes depending on differences in space use. This is particularly true for animals that explore the subterranean niche as it is associated with high travelling costs. In subterranean rodents the complexity of burrow systems varies with differing degrees of sociality possibly posing stronger selective pressures regarding spatial abilities on species with more complex burrow structures.

Malaria: a peek at the var variorum.

Geneticists encountering the diversity of the malaria parasite's var gene family for the first time often complain that its complexity is a nightmare. A new article by Barry et al. presents the latest and most systematic attempt to date to decipher the var variorum.