How viruses and other organisms engage in a biological arms race with one another? By studying the role of the RNASEL gene and its mutations in relation to viral infection and prostate cancer, ZHANG Yaping’s lab at the Kunming Institute of Zoology (KIZ), Chinese Academy of Sciences (CAS) try to give the answer.
The RNASEL gene plays a critical role in combating viral infections. When cells are infected by viruses, interferons induce the expression of OAS (2’, 5’-oligoadenylate synthetase) which activates RNASEL, an enzyme that degrades viral RNA. The important role this gene plays in promoting health is likely why the gene has evolved in so many different organisms—birds, reptiles, and mammals—and why it evolved so rapidly. According to the Red Queen hypothesis, a biological “arms race” occurs between pathogen and host, where each increasingly arms itself and evolves to combat the other. Since the RNASEL gene is involved in combating viruses and viral infection, it is quite possible that it was positively selected and bred into numerous populations. ZHANG’s lab confirmed their speculations on the evolution of RNASEL. They had sequenced the gene in 11 primates, finding a strong genetic basis for the idea that RNASEL is a positively selected trait. But what about humans?
In humans, RNASEL has strong associations with risks of prostate cancer, incidence rates of which vary considerably across different populations. While relatively high in Oceania, North America and Europe, in Africa and Asia, the risks are much lower. Though there are a variety of non-genetic factors that contribute to this—particularly Asian populations’ diet, rich in soy products—DNA sequencing of 144 randomly selected subjects from Africa, Europe, East Asia and South Asia suggested that certain mutations to the RNASEL gene are associated with an increase or decreased risk for prostate cancer.
The DNA sequencing they performed showed that RNASEL genes containing 541D polymorphisms likely have a greater ability to defend against viruses, which are often associated with early stages of prostate cancer. This finding suggests a protective effect of RNASEL mutations,with the 462R-541D substitutions allowing for a more effective activity of the enzyme to defend against infections, thereby substantially reducing the onset of prostate cancer. The RNASEL haplotype 462R-541D likely then evolved because of the advantage it gave in defending against viral infections.
Though previous studies have shown that the evolution of protection against viruses often comes at the cost of developing traits making populations susceptible to cancer, ZHANG’s research proposes a different model, where an evolved defense against viral infections is actually linked to a reduction in the risk of cancer. This new model will likely have significant impact on how we view and understand the co-evolution, or arms race, of organisms and disease.
The research was published in the Society for Molecular Biology and Evolution. http://mbe.oxfordjournals.org/content/early/2012/04/17/molbev.mss123.abstract