Study finds anti-HIV protein evolved millions of years before the emergen...( h parties to the conflict have been cle...)

h parties to the conflict have been clearly identified suggests that some forms of the protein are more effective at overcoming HIV infection than others, which may influence whether a person's disease advances rapidly, said Michael Emerman, Ph.D., an HIV researcher in the center's Human Biology and Basic Sciences divisions and a co-author of the study.

"There is great variation in disease progression among HIV-infected individuals," he said. "This variability is influenced by the type of virus that infects a person as well as by the person's genetic makeup. Increasingly, human genes are being discovered that influence viral progression. Apobec3G is a good candidate to be one of these genes."

The findings are a striking example of what can be learned from studying rapidly evolving proteins, the research approach taken by Malik's lab. Conflicts in nature drive this type of evolutionary change when two competing biological interests come head to head. Predators and prey often influence the evolution of one another, and the same can happen between viruses and proteins of the cells they infect.

"We don't always know what the conflict is, but by looking for proteins that are rapidly evolving in response to selective pressures we can identify candidates that participate in conflict," Malik said. "Some of them will be relevant to disease."

To identify the selective pressure on Apobec3G evolution, Sawyer and colleagues analyzed the genes from 12 primates New World monkeys, Old World monkeys, great apes and humans spanning 33 million years of evolution. This approach allowed them to backtrack through evolution and identify recent genetic changes a well as construct a hypothetical ancestor of all the species.

Most of the primates they examined showed evidence of what is known as positive selection, indicating that the gene has been under pressure to evolve throughout history. But lentiviruses the family of viruses to which HIV belongs have been f
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Contact: Kristen Lidke Woodward
kwoodwar@fhcrc.org
206-667-5095
Fred Hutchinson Cancer Research Center
29-Jul-2004

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