Evolutionary genomics of malaria hosts and parasites
Abstract/Contents
- Abstract
- Malaria caused by the replication of Plasmodium falciparum parasites within human red blood cells (RBCs) remains a leading cause of human death by infectious disease. Over several thousand years, high childhood mortality from malaria has produced strong selection for human resistance, mostly via genetic RBC diseases like sickle cell anemia. On much shorter timescales, anti-malarial drugs have also imposed strong selection on genetic drug resistance in malaria parasites. Therefore, the ultimate goal of malaria elimination can be served by developing treatments and drug policies in the context of the evolution of both malaria hosts and parasites. This dissertation explores the history of genetic adaptation in malaria in three parts. First, I use laboratory experiments to demonstrate that natural, 'healthy' variation in human RBCs has substantial effects on P. falciparum growth rate. This identification of novel, protective alleles and phenotypes that are not strongly deleterious may help lead to new malaria therapies. However, I find little evidence that subtle protective variation has experienced positive selection in Africa. Second, I explore the stronger possibility of host adaptation over deeper time scales using ~9,000 protein sequences from 24 species of mammals infected by Plasmodium or related blood parasites. I find that mammalian proteins linked to malaria in the literature have experienced ~3 times more positive selection in the last 100 million years than proteins that have not. Widespread, non-deleterious host adaptation to malaria is therefore possible, but perhaps not on timescales relevant to humans. Finally, I combine new data and historical records from the west African country of Angola to document the extremely rapid evolution of genetic drug resistance in P. falciparum parasites over the last 20 years. This result suggests that changes in drug administration are badly needed in Angola, where malaria deaths are on the rise. An evolutionary approach to the biological control of malaria will allow for the development of therapies that remain efficacious over time.
Description
| Type of resource | text |
|---|---|
| Form | electronic resource; remote; computer; online resource |
| Extent | 1 online resource. |
| Place | California |
| Place | [Stanford, California] |
| Publisher | [Stanford University] |
| Copyright date | 2020; ©2020 |
| Publication date | 2020; 2020 |
| Issuance | monographic |
| Language | English |
Creators/Contributors
| Author | Ebel, Emily Rose |
|---|---|
| Degree supervisor | Petrov, Dmitri Alex, 1969- |
| Thesis advisor | Petrov, Dmitri Alex, 1969- |
| Thesis advisor | Egan, Elizabeth S |
| Thesis advisor | Mordecai, Erin |
| Thesis advisor | Pritchard, Jonathan D |
| Degree committee member | Egan, Elizabeth S |
| Degree committee member | Mordecai, Erin |
| Degree committee member | Pritchard, Jonathan D |
| Associated with | Stanford University, Department of Biology. |
Subjects
| Genre | Theses |
|---|---|
| Genre | Text |
Bibliographic information
| Statement of responsibility | Emily R. Ebel. |
|---|---|
| Note | Submitted to the Department of Biology. |
| Thesis | Thesis Ph.D. Stanford University 2020. |
| Location | electronic resource |
Access conditions
- Copyright
- © 2020 by Emily Rose Ebel
- License
- This work is licensed under a Creative Commons Attribution Non Commercial 3.0 Unported license (CC BY-NC).
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