By Marlene Cimons, National Science Foundation
The never-ending battle between infectious organisms and the body’s natural defenses is like a molecular arms race where each side struggles to outmaneuver the other.
The factors that determine who ultimately wins—what allows a pathogen such as a virus to change and become more lethal over time, or why an infected host is able to overcome an attack—long have been a mystery to scientists.
Researchers at the University of Utah believe one answer may involve the genetic diversity of the host. They think that genetic variation makes it more difficult for dangerous pathogens to evolve to become stronger and more reproductively robust in their hosts.
The National Science Foundation is supporting the research with a $985,000 grant over five years as part of the American Recovery and Reinvestment Act of 2009.
Mammals, including humans, have extremely high genetic diversity among the genes involved in the immune system, which the scientists think may increase their chances of defeating an infectious opponent, although the outcome is not always certain.
“Viruses are up to no good for us hosts,’’ said Wayne K. Potts, a professor in the department of biology, whose lab is conducting a series of experiments to test the hypothesis. “They are always looking for ways to exploit us, and turn our resources into helping them make more viral babies. A virus can evolve very fast; it goes through a generation in 24 hours. That leaves us in sort of a vulnerable position, since we can only evolve once every 20 years or so.’’
Understanding the mechanisms that encourage viruses and other microorganisms to become more virulent and reproductive ultimately could lead to new approaches in vaccine development, as well as new therapeutics. It also could change how the livestock industry uses antibiotics, particularly as it affects the serious and growing problem of antibiotic resistance. The work even could inspire new approaches for saving endangered species.
For example, “at one point we were down to six condors,’’ Potts said. “Their genetic diversity was remarkably reduced. Consider that 90 percent of our attempts to reintroduce captive species into the wild fail. Why is that? Maybe it’s because they’ve become an easier target for pathogens.’’
This uneasy balance in nature between pathogen and host, and between predator and prey, is also sometimes known as “the Red Queen Hypothesis,” from Alice in Wonderland, when “the Red Queen says to Alice: ‘you have to run as fast as you can to stay in the same place,’’’ Potts said.
The Red Queen hypothesis states that when co-evolving species have conflicting interests, such as between hosts and pathogens, then adaptations and counter adaptations occur endlessly as each species competes for greater success. This may explain why sexual reproduction occurs among higher species, since sexual reproduction produces novel genetic combinations, unlike asexual reproduction.
If no random mixing occurs, then bacteria or parasites could quickly evolve into more virulent or lethal forms, potentially endangering or wiping out a host species. However, sexual reproduction produces offspring whose genotypes differ from both parents, thus creating a moving target for pathogen evolution, which slows down pathogen advances. Thus, sex becomes a critical tool for hosts in their battle against pathogens.
“For years, nobody could understand why sexual reproduction was so pervasive among animals and plants because it involves huge costs,’’ Potts said. “For most species, males do nothing except provide sperm. So, sex must be doing something really important or females wouldn’t be putting up with males; they could evolve through asexual reproduction and get rid of males all together.’’
Potts and his colleagues are testing this hypothesis with two mouse viruses, Friend virus, a strain of murine leukemia virus identified by Charlotte Friend in 1956, and Theiler’s virus, a murine picornavirus, that lives in the digestive system but, like polio, “occasionally goes haywire and gets into the nervous system,” Potts said.
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