Case Studies: Can Malaria Parasites Alter Their Sex Ratios Adaptively?

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Case Studies: Can Malaria Parasites Alter Their Sex Ratios Adaptively?

Can Malaria Parasites Alter Their Sex Ratios Adaptively?

Paul, R. E. L.; Coulson, T. N.; Raibaud, A.; Brey, P. T. 2000. Sex determination in malaria parasites. Science, 287: 128-131.

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Malaria remains one of the most deadly of human diseases, killing a million people per year. In spite of the importance of malaria to human welfare, the causative agents, apicomplexan protozoa in the genus Plasmodium, remain surprisingly poorly known. For example, the exact mechanism of sex determination in these organisms remains a mystery.

The life cycle of species of Plasmodium is complex, with both a vertebrate and a mosquito host needed to complete the life cycle. The Division of Parasitic Diseases of the Centers for Disease Control provides an excellent introduction to malaria and to Plasmodium (http://www.dpd.cdc.gov/dpdx/html/frames/m-r/malaria/body_malaria_page1.htm). Sexual reproduction takes place in the vertebrate blood but in the gut of the mosquito, shortly after the mosquito acquires the infection from the vertebrate host. Previously, scientists have noted that the sex ratio of gametes seen in the mosquito is strongly female-biased. Shortly after formation of the zygote, reductive division takes place; Plasmodium spp. are haploid during most of the life cycle.

Because of the difficulty of studying malaria in humans, scientists have worked extensively with chickens as a model system, using Plasmodium gallinaceum. In chickens, infection with P. gallinaceum yields either of two outcomes: most birds become very sick, and then recover, but some birds do not improve and die relatively quickly. Among the birds who recover, the sex ratio of the parasites shifts toward 1:1 whereas among the birds who die, the sex ratio remains female biased. Richard Paul, Timothy Coulson, Anna Raibaud and Paul Brey undertook a variety of experiments to investigate whether the sex ratio observed in P. gallinaceum is adaptive, and if so, what triggers the shift. The exercises below offer an opportunity to analyze data adapted from the experiments of Paul et al. and to draw your own conclusions regarding how and why sex ratio shifts occur in Plasmodium species.

Is the shift in sex ratio caused by differential mortality of male and female gametes?

One possible explanation for the biased sex ratio observed in the mosquito hosts is that vertebrate immune effectors can kill more male gametes in the gut of the mosquito. To test this possibility, Paul et al. vaccinated chickens with irradiated male or female gametes plus microgametocytes (cells that generate male gametes) in order to generate a strong immune response. They then infected the birds via a blood transfusion. They then compared these birds to a control group, looking at (1) time from first appearance of parasites in the blood to peak parasitemia (the largest number of parasites in the blood), (2) parasite density, (3) gametocyte density, and (4) sex ratio.

Is the shift in sex ratio related to erythropoeisis?

As in human malarias, P. gallinaceum causes anemia as the erythrocytes rupture when parasites emerge. Among the birds who recover, initiation of an immune response coincides with erythropoiesis, the manufacturing of new red blood cells to replace those lost. Paul et al. investigated whether the sex ratio shift observed in recovering birds might be related to erythropoietic activity.

First, in anemic birds in which erythropoeisis has been triggered, there will be a higher proportion of reticulocytes, immature red blood cells. Normally, Plasmodium spp. does not infect reticulocytes unless reticulocytes densities are very high. A possible explanation for the sex ratio shift observed would be that males are disproportionately like to emerge from reticulocytes. Paul et al. investigated this possibility by withdrawing blood from birds and replacing it with reticulocyte - rich blood.

Next, these authors investigated the effects of erythropoiesis on the parasites by inducing erythropoiesis experimentally, either by exposing birds to an oxygen-deficient environment, or by withdrawing blood, both on the day of patency (erythropoiesis).

Although the regulation of erythropoiesis in birds remains poorly understood, the hormone erythropoietin regulates erythropoiesis in mammals. Paul et al. investigated the effects of mouse recombinant erythropoietin (Epo) in two dosages on sex ratio in P. vinckei in mice. The results are summarized in Table 6.

According to Paul et al., the parasites benefit from changing the sex ratio in response to host cues. When the vertebrate host initiates erythropoeisis, more host cells are available for parasites to invade, and more parasites can reach the mosquito. When the vertebrate host does not respond by producing more red blood cells, the number of cells available to infect will decline, and fewer parasites will reach the mosquito host. A female-biased sex ratio will ensure fertilization under increasingly unfavorable conditions for the parasite.

1. Paul et al. observed no difference in time to peak parasitemia, parasite density or gametocyte density for the chickens vaccinated with male gametes or female gametes relative to the control. Why did the authors examine these variables?
To create paragraphs in your essay response, type at the beginning of the paragraph, and at the end.

2. Paul et al. observed no statistically detectable difference in sex ratio for the three treatment groups using a statistical procedure similar to a chi square test. What information does this experiment provide about differential mortality?
To create paragraphs in your essay response, type at the beginning of the paragraph, and at the end.

3. Both vaccine treatments were successful in reducing the infection rates among mosquitoes. Why is this useful to know?
To create paragraphs in your essay response, type at the beginning of the paragraph, and at the end.

4. In comparison to controls, the Plasmodium from birds receiving additional reticulocytes showed no change in sex ratio. What does this indicate?
To create paragraphs in your essay response, type at the beginning of the paragraph, and at the end.

5. Graph the infection parameters from Table 1. Are there any changes in the course or level of infection? Why is this graph useful?
To create paragraphs in your essay response, type at the beginning of the paragraph, and at the end.

6. Graph the sex ratio against the day of infection (Table 2). Are there any differences among the treatment groups? Graph the sex ratio in the control and hypoxic groups against day of patency (Table 3).
To create paragraphs in your essay response, type at the beginning of the paragraph, and at the end.

7. Graph the sex ratio against the day of infection. Are there any differences among the treatment groups?
To create paragraphs in your essay response, type at the beginning of the paragraph, and at the end.

8. Graph the mean oocyst load against the day of infection. (Oocysts are formed in the mosquito host following formation of the zygote; this represents a measure of successful parasite reproduction as well as mosquito infection). What does this graph indicate?
To create paragraphs in your essay response, type at the beginning of the paragraph, and at the end.

9. Calculate 95% confidence intervals for the data points. What additional conclusions can you draw?
To create paragraphs in your essay response, type at the beginning of the paragraph, and at the end.

10. Both treatments, hypoxia and phlebotomy, resulted in statistically significant changes in parasite sex ratios. What does this indicate?
To create paragraphs in your essay response, type at the beginning of the paragraph, and at the end.

11. Does Epo alter the sex ratio of P. vinckei? Does the effect depend on the dosage?
To create paragraphs in your essay response, type at the beginning of the paragraph, and at the end.

12. How would you interpret these observations?
To create paragraphs in your essay response, type at the beginning of the paragraph, and at the end.

13. Chloroquine, a drug commonly used to treat malaria, suppresses erythropoietin synthesis. What effects might this have on the host and on the parasite?
To create paragraphs in your essay response, type at the beginning of the paragraph, and at the end.

14. In Chapter 8 of the textbook, the authors argue that every adaptive explanation must be tested. Have Paul et al. met the requirements for testing of an adaptational hypothesis?
To create paragraphs in your essay response, type at the beginning of the paragraph, and at the end.




1.	Paul et al. observed no difference in time to peak parasitemia, parasite density or gametocyte density for the chickens vaccinated with male gametes or female gametes relative to the control. Why did the authors examine these variables? To create paragraphs in your essay response, type <p> at the beginning of the paragraph, and </p> at the end.



2.	Paul et al. observed no statistically detectable difference in sex ratio for the three treatment groups using a statistical procedure similar to a chi square test. What information does this experiment provide about differential mortality? To create paragraphs in your essay response, type <p> at the beginning of the paragraph, and </p> at the end.



3.	Both vaccine treatments were successful in reducing the infection rates among mosquitoes. Why is this useful to know? To create paragraphs in your essay response, type <p> at the beginning of the paragraph, and </p> at the end.



4.	In comparison to controls, the Plasmodium from birds receiving additional reticulocytes showed no change in sex ratio. What does this indicate? To create paragraphs in your essay response, type <p> at the beginning of the paragraph, and </p> at the end.



5.	Graph the infection parameters from Table 1. Are there any changes in the course or level of infection? Why is this graph useful? To create paragraphs in your essay response, type <p> at the beginning of the paragraph, and </p> at the end.



6.	Graph the sex ratio against the day of infection (Table 2). Are there any differences among the treatment groups? Graph the sex ratio in the control and hypoxic groups against day of patency (Table 3). To create paragraphs in your essay response, type <p> at the beginning of the paragraph, and </p> at the end.



7.	Graph the sex ratio against the day of infection. Are there any differences among the treatment groups? To create paragraphs in your essay response, type <p> at the beginning of the paragraph, and </p> at the end.



8.	Graph the mean oocyst load against the day of infection. (Oocysts are formed in the mosquito host following formation of the zygote; this represents a measure of successful parasite reproduction as well as mosquito infection). What does this graph indicate? To create paragraphs in your essay response, type <p> at the beginning of the paragraph, and </p> at the end.



9.	Calculate 95% confidence intervals for the data points. What additional conclusions can you draw? To create paragraphs in your essay response, type <p> at the beginning of the paragraph, and </p> at the end.



10.	Both treatments, hypoxia and phlebotomy, resulted in statistically significant changes in parasite sex ratios. What does this indicate? To create paragraphs in your essay response, type <p> at the beginning of the paragraph, and </p> at the end.



11.	Does Epo alter the sex ratio of P. vinckei? Does the effect depend on the dosage? To create paragraphs in your essay response, type <p> at the beginning of the paragraph, and </p> at the end.



12.	How would you interpret these observations? To create paragraphs in your essay response, type <p> at the beginning of the paragraph, and </p> at the end.



13.	Chloroquine, a drug commonly used to treat malaria, suppresses erythropoietin synthesis. What effects might this have on the host and on the parasite? To create paragraphs in your essay response, type <p> at the beginning of the paragraph, and </p> at the end.



14.	In Chapter 8 of the textbook, the authors argue that every adaptive explanation must be tested. Have Paul et al. met the requirements for testing of an adaptational hypothesis? To create paragraphs in your essay response, type <p> at the beginning of the paragraph, and </p> at the end.

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Case Studies: Can Malaria Parasites Alter Their Sex Ratios Adaptively?