Transported and delivered by mosquitos, the protozoan parasite Plasmodium falcipanum causes malaria in humans.
Numerous antimalarial medications have been tried. Quinine was the first, beginning in the 17th century.
Invariably the parasite evolves resistance to these drugs. This is peculiar because Plasmodium are haploid. Lacking meiosis, each generation is ostensibly a clone of its parent. But adaptation still occurs.
One treatment tested against Plasmodium involved inhibiting the enzyme required for biosynthesis of nucleic acids and a precursor, pyrimidine. (The nucleobases for cytosine, thymine, and uracil are pyrimidine derivatives.) Plasmodium developed resistance, but not by point mutation, where a new base nucleotide is substituted for the old. Instead, multiple copies of the gene for making the specific enzyme appeared, allowing production of the requisite enzyme. This was a pre-adaptation aimed at contingency flexibility.
The genic copies were constructed during mitosis by rearranging scattered RNA segments. Further, the number of copies made go up or down depending on drug pressure. Adaptive resistance by Plasmodium is specific and based upon risk assessment.