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.
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