Thursday, November 5, 2015

C. Miguel Pinto, the Disease Detective

Fig.1. Red Queen lecturing Alice (Credit: John Tenniel, 1871)

“Now, here, you see, it takes all the running you can do to keep in the same place,”
- Lewis Carroll’s Through the Looking Glass

In Lewis Carroll’s Through the Looking Glass, Alice once again finds herself in a fantastical world. A chess piece called the Red Queen describes the rules of the Looking-Glass land, claiming that no matter how far Alice runs, the girl will stay in the same place. Evolutionary biologist Leigh Van Valen adopted this story in 1973 to illustrate the concept of an evolutionary arms race in which species must constantly evolve to remain extant. In symbiotic relationships, like that of parasites and hosts, an adaptation in one will affect the other. Therefore these organisms continually evolve, or “run,” to counter pressures posed by the opposite in order to survive.

This type of relationship fascinates C. Miguel Pinto, a George E. Burch and Peter Buck Postdoctoral Fellow at Smithsonian’s National Museum of Natural History (NMNH). He explores the evolutionary underpinnings of mammals and the parasites they hold. In particular, Pinto studies Trypanosoma parasites in bats.

“I’m interested in analyzing some genes associated with the immunity function in mammals and see if there is an arms-race between the immunity of mammals and the genes associated with infection in trypanosomes,” he said.

Fig.2. Blood smear from patient with African trypanosomiasis,
or sleeping sickness. (Credit: CDC/Schultz, 1970)

Trypanosomes are unicellular parasites in the genus Trypanosoma and are responsible for such deadly diseases as sleeping sickness (Trypanosoma brucei) and Chagas disease (Trypanosoma cruzi), an important parasitic disease in the New World. Understanding how they adapt to overcome mammal defenses in the evolutionary “arms-race” is a valuable insight for disease research and response efforts.

This coevolution between bats and trypanosomes is especially interesting for Pinto, given the species’ long history of association. His recent work in Panama suggests that the parasites have experienced multiple dispersal events to the  Americas, starting a few million years ago. Pinto and his colleagues discovered five different species of trypanosomes in one bat species, a startling discovery because the ratio is usually one-to-one.

The sheer diversity between the five species in one bat means that the parasites probably arrived in the New World at different times, from ancient history to much more recent. Pinto thinks that bats carried trypanosomes from Africa to South America in waves, either across the Atlantic Ocean or through Asia and Beringia. The exact mechanisms and dates, however, are difficult to pin down.

“The timing is tricky because actually calibrating with really good confidence with that molecular clock is becoming really challenging because we don’t know a good mutation rate for the genes we are using,” Pinto said.

Fig.3 Sign with the “kissing bug” (triatomine bug) that acts
as a vector for trypanosomes (Credit: Daniel Neal via Flickr, 2014)

Luckily, Pinto is in a good place to uncover the complexities of evolutionary history. NMNH holds a collection of around 140,000 bat specimens and their associated data, which provides an invaluable resource. His work to analyze the coevolution and diversity in mammals and parasites has been grounded in museum collections since his masters program at Texas Tech University and research for his dissertation in the American Museum of Natural History through the City University of New York.

“Probably if I could sum up all of the expenses that those field crews have spent collecting those samples, it would be an unbelievable amount of money,” he said.

Although Pinto has worked with trypanosomes since his undergraduate years, he wants to explore other collections and diseases. One anticipated challenge is recovering enough genome-quality material in the museum to do thorough analyses of specimens. For RNA viruses in particular - a group that includes Ebola, SARS, influenza, and polio - Pinto worries about completing similar research as he did with Trypanosoma lineages. Newer practices in collecting, however, are helpful.

“The good thing is that museum collections are realizing that it is very important to preserve more tissues in liquid nitrogen and to preserve genome quality material. That would help us to truly study these viruses,” Pinto said.

At the interface of wildlife and human diseases, collections offer an eye into the past and show patterns previously unseen. With colleagues at the National Zoological Park, the molecular labs of NMNH, and in museums around the world, Pinto hopes to put pathogens in an evolutionary and historical context. The possible switch to other types of diseases beyond parasitic does not worry him, rather he looks forward to similar detective work in other specimens. After all, bats and trypanosomes are not the only species involved in an "arms-race."

“That would be very interesting to see, just to use the museum collections more for this kind of research and to understand it in other diseases,” said Pinto.


References:
Carroll, L. (1872). Through the Looking-Glass and What Alice Found There. London: Macmillan.

Coevolution. [n.d.]. Understanding Evolution. University of California, Berkeley. Retrieved from http://evolution.berkeley.edu/evolibrary/article/evo_33

Cottontail, V. M., et al. (2014, September). High local diversity of Trypanosoma in a common bat species, and implications for the biogeography and taxonomy of the T. cruzi clade. PLOS One, vol. 9 (9). e108603. doi:10.1371/journal.pone.0108603

Lively, C. M. [n.d.]. Red Queen Hypothesis. Indiana University. Retrieved from http://www.indiana.edu/~curtweb/Research/Red_Queen%20hyp.html

Matthews, K. R. W., & Herricks, J. R. (2015). Chagas Disease: Sharing the Burden and the Solutions in the United States and Mexico. Policy Brief no. 10.30.15. Rice University’s Baker Institute for Public Policy: Houston, Texas.



Glossary

extant
Currently living, not extinct
symbiotic
A close interaction or relationship between two different species. This involves benefit to both species (mutualism), benefit to one species while the second is unaffected (commensalism), or benefit to one species while the other is harmed (parasitism)
coevolution
Two (or more) species evolve reciprocally in response to one another

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