Question

Malaria is a disease that is caused by the eukaryotic parasite Plasmodium and is transmitted between individuals by the bite of infected mosquitoes. Different species of Plasmodium cause disease in different vertebrate species, but in all cases the parasite infects and destroys red blood cells. The repeated emergence of drug-resistant strains of Plasmodium parasites responsible for human infections has caused researchers to continually search for new drugs or combinations of drugs that can provide an effective treatment. A drug that has proven effective in recent years is artesunate, but now artesunate-resistant Plasmodium strains have also appeared.

Researchers investigated whether artesunate-resistant Plasmodium strains could be effectively treated by other drugs. In a mouse model of malaria, the researchers determined that a particular strain of artesunate-sensitive Plasmodium (ART-S) could be largely eliminated from the mice at a dose of 0.15 mg/kg. By repeated exposure of the artesunate-sensitive strain ART-S to increasing concentrations of artesunate, the researchers developed a Plasmodium strain that is highly resistant to artesunate (ART-R) and requires a minimum dose of 240 mg/kg to eliminate the parasites.

The researchers then compared how effectively several common antimalarial drugs eliminate the ART-S and ART-R strains in vitro. The researchers infected human red blood cells with the ART-S and ART-R Plasmodium strains and incubated the infected cells in tissue culture medium. They added serial dilutions of the drugs to replicate cultures and determined the IC50 for each drug, the concentration of the drug that reduced the parasite load in the red blood cells by 50% (Table 1).

Table 1. IC50 for common antimalarial drugs tested on artesunate-sensitive (ART-S) and artesunate-resistant (ART-R) Plasmodium strains

Drug	ART-S: IC50±2SEx¯ (nM)	ART-R: IC50±2SEx¯ (nM)
Amodiaquine	11.3 (0.8)	132.4 (16.9)
Chloroquine	50.1 (3.6)	53.0 (11.3)
DHA	13.8 (0.7)	49.5 (6.8)
Mefloquine	41.7 (2.7)	39.1 (5.4)
Quinine	49.7 (3.1)	216.9 (81)

1. Plasmodium is an organism with both sexual and asexual life cycles. Describe the most likely cause of a heritable phenotypic change in some members of a population of asexually reproducing organisms. Explain how repeated exposure of the artesunate-sensitive Plasmodium strain to increasing concentrations of artesunate led to the development of the artesunate-resistant Plasmodium strain.

2. Based on the data, identify the drug that, from the ART-S strain to the ART-R strain, has the largest relative increase in the IC50. Based on the information provided about the mouse model, calculate how many times more sensitive the originalART-S Plasmodium strain is to artesunate than is the ART-R strain.

3. In the mouse model of malaria, the researchers injected Plasmodium-infected human red blood cells into the mice because the Plasmodium species had surface ligand proteins that bound only to cell membrane proteins of human red blood cells. Assume that the researchers noticed that some of the parasites no longer infected human red blood cells but instead infected mouse red blood cells. Predict the most likely cause of this change in the host specificity of the parasites. Plasmodiumreproduces both sexually in the host vertebrate and asexually in mosquitoes. The researchers claim that the Plasmodium organisms that infect the two different types of red blood cells are likely to evolve into two separate species of Plasmodium. Based on the biological species concept, provide reasoning that would support the researchers’ claim.

Answer 1

1.The most likely reason of heritable phenotypic change in asexual organisms can be due to epigenetic changes which involves change in phenotype without change in genotype as the asexual organism dont have meiosis so epigenetics resetting not possible.The increasing concetration of artesunate led to the survival of those plasmodium who could tolerate without dying increasing levels of artesunte so overtime these plasmodium formed progenies which were resistant to much higher levels of artesunate as resistance is heritable trait.

2The Quinine drug has the highest increase in IC50 value from plasmodium sensitive to resistant strain.Dividing the increase 81 by 3.1 means around 26 fold times sensitivity difference in sensitive stain to resistant strain.

3.This is possible that the plasmodium which infected the mouse RBCs for experimental purposes became a new species altogether.As they got seprated from the original plasmodium population so they were not able to sexually mate with them.So over time due to various factors like genetic drift a reproductive barrier got developed between them.As this barrier developed they were no longer able to mate even when mixed with the original parental population as reproductive barriers did not allowed to do so.Hence resulting in the process of speciation and development of two different plasmodium species.