Malaria Paper Questions

1. According to another paper (PNAS “Systemic lupus erythematosus-associated defects in the inhibitory receptor FcyRIIb reduce susceptibility to malaria” by Clatworthy et al. 2007), systemic lupus confers some immunity to malaria.  Geographically, where would you expect the disease alleles to be common, and why?  Considering what you know about sickle cell anemia, how do you hypothesize that this immunity is conferred?

The alleles for systemic lupus most likely would occur in areas of Africa, Asia, and South America. They may be common because those that survive after a infection of Malaria can then pass on those same genes on to their children. A survivor that has systemic lupus also has better immunity to Malaria making them have overall better fitness (ability to pass on their genes through reproduction) in those areas where Malaria is deadly. 

Our original hypothesis was that the parasite cannot live as well on sickle cells than on the regular re blood cells or non-sickle cell carriers. This may not allow the parasites to infect as many cells and would reduce the overall infection. However, after doing some research we found that the "heme oxygenase-1 (HO-1), an enzyme whose expression is strongly induced by sickle hemoglobin. This enzyme, that produces the gas carbon monoxide, had been previously shown by the laboratory of Miguel Soares to confer protection against cerebral malaria" (Ferreira, 2011). The research done by this group showed that the carbon monoxide protects the host against cerebral Malaria, which in many cases can become deadly. 

     2.  In an evolutionary sense, why is it informative to study malaria and its implications in mice?

It is important to study malaria in mice because it can allow us to determine which methods may or may not work according to how the parasite reacts. Studying the mice allows for us to see how quickly the parasite evolves. Studying malaria in mice allows a controlled environment that allows scientist to collect consistent data in a host with a well-known genetic sequence.

3. Apply Darwin’s four postulates to within-host Plasmodium virulence and transmission success.

Individuals within species vary- some Plasmodium individuals have higher virulence and better transmission rates and therefore vary.

Some of these variations are passed on to offspring- The individuals that have a higher virulence and a higher rate of transmission are more likely to pass their genes on to their offspring due to a higher fitness level. Those individuals that have the highest virulence have a better chance of passing on their prominent genes.

Individuals vary in their fitness.

Most favorable adaptations are most likely to survive and reproduce.

4. On page 973, the authors assert that “drug resistance becomes a problem within 5-30 years of first using a drug” and that this “is indicative of their potential to evolve rapidly.”  What does this tell you about the efficacy of vaccines?  Why should your Tropical Medicine physician know about evolution?

This tells us that vaccines are lacking the ability to block all aspects of malaria. It also shows that malaria is evolving rapidly and developing ways to get around vaccines. A Tropical Medicine physician should know how evolution works and keep in mind the effects of it as well. They should know of selection, mutations, and variation among populations. 

  

      5. If, as the authors suggest, more virulent strains have a competitive advantage within their mouse host, why do they conclude that “parasites evolve some intermediate level of virulence”?  What mode of selection on this quantitative trait does this exemplify?

The optimal level of virulence is determined by the selective pressures at both the host and population levels. Natural populations are characterized by a distribution of parasite strains, shaped by parasite traits and selective pressures experienced by parasites. Evolutionary actions also have a vital effect on virulence evolution. The trade-off between the two leads to maximum parasite fitness at intermediate levels of virulence. This is a prime example of stabilizing selection where fitness increases at the intermediate level.

     6. Why is it important to study protein folding/misfolding in malaria, even though we know its  cause?

It is important to study the protein folding and misfolding because it can show how the mutations can change the protein sequence. These changes in protein sequence or changes in protein folding can change how the protein acts.

1. Ana Ferreira, Ivo Marguti, Ingo Bechmann, Viktória Jeney, Ângelo Chora, Nuno R. Palha, Sofia Rebelo, Annie Henri, Yves Beuzard, Miguel P. Soares. Sickle Hemoglobin Confers Tolerance to Plasmodium Infection. Cell, Volume 145, Issue 3, 398-409, 29 April 2011 DOI: 10.1016/j.cell.2011.03.049