January 23, 2020

Can evolution help us cure malaria?

Microbiologist Jonathan Eisen explains one reason to better understand evolution is to develop "new drugs and treatments for diseases that affect millions of people."

Why teach evolution? Here is one reason, from the introduction to the textbook, Evolution, that I coauthored:

Because closely related organisms tend to have similar biological features, evolutionary classification can help predict the biology of an organism through comparison with its relatives. The great majority of microbes on this planet have yet to be cultured, which makes it difficult to study their physiology. Using molecular biology methods, genes from unculturable species can be cloned and evolutionary analysis of those genes provides the information to place the unculturable microbes into a tree of life. This permits closely related species to be identified, including ones whose biology has been studied. For example, this approach has led to the development of new drugs to treat malaria.

The causative agent of malaria is a quite unusual organism in terms of its biology and also its evolutionary history, and understanding its unusual evolutionary history turns out to be critical for developing drugs to treat malaria.

Malaria is caused by the infectious eukaryotic parasite Plasmodium falciparum. Because humans are also eukaryotes, humans and P. falciparum share many aspects of their biology. Therefore drugs that have been developed to kill the parasite frequently are quite toxic to humans as well.

So the first part of this story is that, like us, Plasmodium falciparum is a eukaryote, a member of one of the major lineages of life on this planet. And this helps to explain why some drugs that target the malaria parasite are also toxic to humans.

Malaria death rates by age.

 

But the second part of this story is way weirder, and much more interesting. You might know that animal cells (and other eukaryotic cells) contain mitochondria, a specialized subcompartment of the cell (also known as an organelle) that is used for cellular energy metabolism. Mitochondria actually once were free-living bacteria that were captured by, and brought into the cells of, the common ancestor of all eukaryotes. Mitochondria even have their own separate DNA, left over from when they were free-living organisms. You may also know that plants and their relatives have another specialized subcompartment in their cells (in addition to mitochondria) called the chloroplast, which is where photosynthesis occurs. The chloroplast also once was a free-living bacterium and it was captured by the common ancestor of all plants. And here is where the second part of the malaria story comes into play:

In the 1970s, scientists studying an unusual substructure within the P. falciparum cell found that this organelle contained its own DNA. Much to their surprise, evolutionary trees of genes in this DNA indicated that this essential organelle, the apicoplast...was actually closely related to chloroplasts of plants.

This was significant, because plant chloroplasts originated from an endosymbiosis between plant ancestors and a bacterium related to modern-day cyanobacteria (Chapter 6). Evolutionary analysis has now shown that the Plasmodium lineage obtained this plastid by entering into a symbiosis with another eukaryote (most likely an alga) that contained a plastid.

That’s right. The parasite that causes malaria, even though it is not a plant and cannot carry out photosynthesis, has an organelle related to the plant organelles that carry out photosynthesis. (Quick aside: if humans had chloroplasts, could we just sit in the sun and make sugar instead of eating candy bars? Discuss.) Back to the textbook:

While the exact origins of the apicoplast in P. falciparum are still not known, the finding has revolutionized the search for chemotherapeutic agents to treat malarial infections. New drugs are being tested that target the apicoplast and that therefore have fewer side effects on humans. For example, the herbicide Roundup, which targets the chloroplasts of weedy plants, also kills P. falciparum. Relatives of P. falciparum cause many other diseases, and so chloroplast-targeted drugs may work against them too.

So why teach evolution? Well, first, it is just plain cool that many of the life forms we see around us arose from complex, strange, symbioses between completely different life forms. That’s just pretty amazing. And, second, beyond the “whoa” factor, this knowledge has practical consequences, giving researchers promising pathways to follow as they seek to develop new drugs and treatments for diseases that affect millions of people. That’s a good enough reason for me.

Dr. Jonathan Eisen

Jonathan Eisen is a Professor at the University of California, Davis, with appointments in the Genome Center, the Department of Evolution and Ecology, and the Department of Medical Microbiology and Immunology. His current research focuses on the evolution, ecology and function of communities of microbes and how the microbes interact with each other and with hosts. Most of his work involves the use of high-throughput DNA sequencing methods to characterize microbes and the use and development of computational methods to analyze this type of data. In addition to his research, he is heavily involved in science communication and open science activities.