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Clues Could Aid Human Health
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A tiny mouse living high in the mountains is providing evolutionary clues that might someday help people with blood and lung disorders.

UNL evolutionary biologist Jay Storz is comparing the genetics of deer mice living at high altitudes with their relatively oxygen-rich lowland cousins to understand how animals evolve to adapt to low-oxygen environments. A $220,774 American Recovery and Reinvestment Act (ARRA) grant from the National Heart, Lung, and Blood Institute is enabling Storz and colleagues to expand their ongoing, NIH-funded research.

“This funding allows us to add a new dimension to the research,” Storz said.

Evolutionary insights from this work could lead to treatments for health problems such as chronic obstructive pulmonary disease (COPD), the fourth-leading cause of death in the U.S. COPD and other chronic lung disorders costs the U.S. millions in healthcare and lost worker productivity.

Storz's team is investigating hemoglobin, a protein that binds with oxygen in the lungs and transports it throughout the bloodstream. When oxygen is scarce, animals must take greater advantage of the available supply. High-altitude mice have evolved the ability to maximize the uptake of oxygen they breathe by more efficiently capturing the available oxygen.

The ability to capture and circulate more oxygen could help people with diseases such as anemia, cardiovascular disease and COPD that reduce oxygen transport efficiency. Understanding the mechanisms responsible for evolutionary adjustments in hemoglobin function can be used to design therapies, such as blood substitutes, that can either increase or decrease hemoglobin's ability to bind oxygen in humans.

Storz collaborates with UNL School of Biological Sciences colleague Hideaki Moriyama, a protein expert. They're combining evolutionary biology with experimental biotechnology to identify the genetic mutations responsible for changes in hemoglobin function and to understand how those mutations function together to produce those changes.

The ARRA funding gave the collaborators the opportunity to expand their research to look at changes in protein expression in addition to protein structure through the purchase of new equipment from U.S. companies.

Storz also was able to retain his postdoctoral technician, whose two-year NSF fellowship had just ended. “The funding's timing was perfect to keep her working in the lab.”

Undergraduate student Joshua Allison also has benefited with an ARRA-funded job in the lab, gaining valuable experience for his future career.

“The hemoglobin system in high-altitude deer mice illustrates the solution that evolution has come up to deal with hypoxia (oxygen deficiency),” Storz said. “Our insights may help guide the design of synthetic blood substitutes.”

They're making progress. The team identified mutations in four hemoglobin genes that enable high-altitude deer mice to tolerate chronic hypoxia. These findings were reported in the Proceedings of the National Academy of Sciences.

This article originally appeared on the University of Nebraska-Lincoln website. Reposted with permission.

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