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Study sheds light on evolutionary history, modern-day threats

Phoenix, AZ, December 21, 2004-Researchers at the Translational Genomics Research Institute (TGen), Northern Arizona University and their colleagues today reported results of genetic tests that analyzed plague populations in order to better understand the pathogen's evolutionary history. The information could help determine the origins of modern-day outbreaks and identify the devastating pandemic waves that decimated Europe, Asia and North Africa centuries ago. The results were published in the December 21 issue of the journal Proceedings of the National Academy of Sciences (PNAS).
Plague, caused by the bacterium Yersinia pestis, has impacted humans for thousands of years. It most likely originated between 1,500-20,000 years ago in Africa and since then, has caused millions of deaths across Europe and central Asia.

Plague remains a viable threat today. The disease is second on the federal bioterrorism bacterial threat list, preceded only by anthrax. "There are very few human cases of plague so how do we prepare for a biological attack? First we analyze populations of plague, then we develop tools that allow us to differentiate weaponized strains from those that occur in nature," says the paper's senior author Dr. Paul Keim, Director of Pathogen Genomics at TGen and a faculty member at the Northern Arizona University.

Keim analyzed eight populations of plague and grouped them together based on similarities in their genetic signatures. Y. pestis is often subdivided into three classical biovars. Biovars are traditional classification categories that separate microbes based on differences in physiology. However, Y. pestis is only partially compatible with this system of classification. Subdividing plague by its molecular signature more accurately reflects the pathogen's evolution.

According to Keim, "A genetic signature helps define individual plague populations with incredible precision. If a bioterrorism event does occur, we can now rapidly identify and categorize the pathogen, including potentially its origin."

This research was a joint effort between scientists from the Department of Molecular Biology at the Max-Planck Institute in Berlin, Germany, the Yersinia Research Unit at the Institut Pasteur in France, the U.S. Army Medical Research Institute of Infectious Disease and TGen.

Despite its major impacts on human populations, plague today is primarily a disease of rodents and their associated fleas. Many North American rodents are highly susceptible to plague and experience massive population die-offs after exposure. In separate study designed to further identify the evolutionary history of plague, Keim monitored plague-infected fleas found on prairie dogs to determine transmission dynamics of the disease. In a paper published in the June 1, 2004 issue of PNAS, Keim and his team developed a model for determining the origins of a particular strain of plague, how long it's been in existence and ultimately whether it is weaponized or naturally occurring.

About TGen
TGen is a not-for-profit research institute whose primary mission is to make and translate genomic discoveries into advances in human health. Translational genomics research employs innovative advances arising from the Human Genome Project and applies them to the development of diagnostics, prognostics, and therapies for cancer, neurological disorders, diabetes and other complex diseases.

About NAU
NAU has earned a solid reputation as a comprehensive university with a personal touch and an outstanding research component. The personal attention comes in many forms, including small classes with full-time professors who know their students' names and a caring and committed staff whose goal is to help every student succeed. While our emphasis is undergraduate education, we offer graduate programs and research that build from our base on the Colorado Plateau and extend to such national concerns as forest health and genetics. www.nau.edu. Internationally recognized environmental research, including disease ecology, programs give student unique training opportunities.


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