Rapid evolution of a protein produced by an immunity gene is associated with increased antiviral activity in humans, a finding that suggests evolutionary biology and virology together can accelerate the discovery of viral-defense mechanisms, according to researchers at Fred Hutchinson Cancer Research Center.
These findings by Julie Kerns, Ph.D., a postdoctoral researcher in the Hutchinson Center's Basic Sciences Division, published Jan. 25 in the open-access journal PLoS Genetics, present a striking example by which evolutionary studies can directly lead to biomedically important discoveries in the field of infectious diseases.
The immunity gene, called ZAP, is a key player in a newly discovered branch of antiviral defenses in mammals referred to as ‘‘intrinsic immunity.'' Host proteins like ZAP can target intracellular stages of the viral life cycle to inhibit viral activity. The ZAP gene, first discovered in rats, thwarts a variety of divergent viruses, from retroviruses (like HIV) to alphaviruses (like Sindbis) to filoviruses (like Ebola).
Researchers believe ZAP functions by virtue of its RNA-binding abilities, which recognize specific sequences of the virus and target their viral RNA for destruction. Host-virus interactions are a classic example of genetic conflict in which both entities try to gain an evolutionary advantage over the other. This ‘‘back-and-forth'' evolution is predicted to result in rapid changes of both host and viral proteins, which results in an evolutionary signature of positive selection, especially at the direct interaction interface.
“This suggests that we might be able to deduce host-virus conflicts purely by looking at rapidly evolving protein segments,” said Kerns, the lead author of the study, which was conducted in collaboration with senior author Harmit Singh Malik, Ph.D., of the Center's Basic Sciences Division and co-author Michael Emerman, Ph.D., of the Center's Human Biology Division.