Mechanisms of Evolution:
Genetic diversity in malaria parasites

Malaria parasites in humans have single copies of most essential genes, yet they can mutate at extraordinary rates without much damage to themselves. We have demonstrated that as few as 100,000 parasites can evolve in a single culture flask to become resistant to an antimetabolite they have never seen before. We have called this the ARMD trait, for Accelerated Resistance to Multiple Drugs. It’s a population-based strategy where individual parasites modify one randomly chosen site in the genome to get a genetic foothold. We hypothesize that the initial change is a duplication of a cluster of genes, and this is followed by expansion of the amplicon, point mutations within the amplicon, and final resolution back to single copies. Current interests are to determine the molecular players involved in the process and to evaluate the distribution of ARMD traits in field settings.

Representative Publications

Rathod, P. K., Mcerlean, T. & Lee, P. C. Variations in frequencies of drug resistance in Plasmodium falciparum. Proceedings of the National Academy of Sciences of the United States of America 94, 9389–9393 (1997).

Ganesan, K. et al. A genetically hard-wired metabolic transcriptome in Plasmodium falciparum fails to mount protective responses to lethal antifolates. PLoS Pathogens 4, (2008).

Guler, J. L. et al. Asexual Populations of the Human Malaria Parasite, Plasmodium falciparum, Use a Two-Step Genomic Strategy to Acquire Accurate, Beneficial DNA Amplifications. PLoS Pathogens 9, (2013).