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Grant to Understand RNA Mutations Could Help Explain Evolution of Life

By: Cienna Madrid   Published 11:41 am / April 5, 2018

Boise State’s second annual Research Month is April 2018. Research Month celebrates the diverse and fascinating array of research happening each day on campus. Read feature stories on Boise State’s research endeavors, and access a full list of Research Month events, online at: research.boisestate.edu

Portrait of Eric HaydenEven as researchers search for signs of life elsewhere in the universe, fundamental questions about how life can begin have yet to be answered. Fortunately, institutions including NASA fund research on the origin and early evolution of life. Understanding how life can begin will help define what makes Earth habitable, and help define where to look for life elsewhere in the universe as well as what to look for.

Boise State’s Eric Hayden, an assistant professor of biology, recently was named principal investigator of a three-year, $661,104 grant from NASA to study how early mutations in ribonucleic acid (RNA) molecules could have given rise to the evolution of life on Earth. His research is in collaboration with Andreas Wagner from the University of Zurich, Switzerland. The grant will support a post-doctoral researcher (Clementine Gibard) as well as students working toward graduate degrees.

“I’ll be studying how genetic changes, or mutations, interact with environmental changes,” Hayden explained. “There is a paradigm well accepted in ecology and evolution that the traits we observe in living organisms are not only dependent on genes but the environment those genes reside in. This research will take this concept down to the molecular level to see how RNA interacts with the environment, and when we manipulate that environment, to see what new structures and functions are present.”

Living organisms require numerous enzymes. In the origins and early evolution of life, these enzymes were thought to be predominantly RNA molecules. Through his research, Hayden will investigate how environmental change alters the properties of RNA molecules, which enable them to evolve new functions. Hayden will use modern “high-throughput sequencing” technologies to make billions of measurements of RNA molecules that are evolving in a test tube. From this, he will be able to look at how mutations and the environment interact to produce functional molecules.

As a model environmental variable, Hayden will alter the amount of the chemical element magnesium. Magnesium is necessary for RNA to fold and carry out its function. Hayden will look at that exact same collection of molecules and change the environment ­– i.e. the magnesium levels – in a systematic way to observe how RNA molecules respond. By assigning a relative activity, or “fitness” to each sequence, Hayden will be able to construct empirical fitness landscapes that unfold into peaks and valleys depending on magnesium levels. For a given RNA sequence, fitness will change if the reaction conditions change.

This video, created by Bjørn Østman and Randy Olson, gives a good visual representation:

“Some molecules will require vary little magnesium to maximize their function, but they may not ultimately be as good as molecules that require more magnesium,” Hayden explained. “These gives one the image of an undulating landscape, the peaks in the fitness landscape are changing in response to the amount of magnesium. These have been called ‘seascapes’ instead of ‘landscapes.’”

In addition, interactions with collaborator Andreas Wagner will be important for advancing computational tools needed to analyze and visualize the results of the research. The project will require computational data analysis and the modeling of evolution, which “will contribute to our efforts on campus to expand the computational capacity of students and researchers,” Hayden explained.