Ancient viral genes have evolved to defend the brain against present-day infections

Two genes from millions of years ago found in mice help to protect their brain against new infections.
Brittney Grimes
A Strand of DNA

DNA Strand 

New viruses can threaten our immunity and impact our livelihood. However, a new study is showing promise that our bodies may be able to defend against such future infections. The study, published in Development, looks at two mouse genes left behind by infection millions of years ago and their development in protecting the brain against new infections.

Analysis and research team

Viral genes often incorporate themselves into the DNA of their host. This leads to the evolution of viral genes and allows them to be passed down through generations. This new study shows the evolution of the two mouse genes, allowing the researchers to study the significance of these genes in fighting infections within the brain. The research was led by Dr. Fumitoshi Ishino, professor of Molecular Biology at Tokyo Medical and Dental University in Japan, and Dr. Tomoko Kaneko-Ishino, professor of Molecular Biology at Tokai University in Kanagawa, Japan.

The two genes

The genes studied, known as retrotransposon Gag-like (RTL) genes, are carried by almost all mammals, including humans and mice as mentioned in this study. The two genes are retrotransposon Gag-like 5 (RTL5) and 6 (RTL6) and are derived from similar genes found in retroviruses, such as HIV. The researchers knew that these two genes were significant because they were inherited viral genes preserved for at least 120 million years, despite coming from viruses. The scientists needed to find the exact location of RTL5 and 6 in order to figure out what the genes were doing. “Two phylogenetically related retrovirus-derived genes, RTL5 and RTL6, play important roles in the front line of the innate brain immune response,” said Ishino and Kaneko-Ishino.

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Ancient viral genes have evolved to defend the brain against present-day infections
RTL6 proteins, shown in green, guard the mouse brain against infection by clustering around the magenta-colored infection

The scientists further analyzed and studied RTL5 and 6 proteins. They found that these two genes are turned on in brain cells called microglia. “Microglia are the primary innate immune cells of the brain and play a central role in the immune responses to various pathogens via a variety of Toll-like receptors,” the study stated. The researchers created fake infections within the mice brains to test how responsive microglia comprising of RTL5 or 6 would be in response to viruses.

First test of its kind

This research study is the first of its kind to show that genes derived from viruses can protect the brain against infections. It is almost a paradox to realize that a virus, something we don’t think highly of in terms of healing, could possibly offer a key to the defense and development of humankind.

“I think that our series of work on RTL genes provided evidence that mammalian-specific genes from retroviruses are very important in elucidating mammalian-specific functions in development. I think that this concept is a key to link ontogeny (development) and phylogeny (evolution) in current genome biology,” Ishino said. “We assume that primate- and human-specific genes from retroviruses have important roles in the creation of several human features as well as the evolution of humans. It should be a neo-human genome project and we hope that many young researchers will want to be involved in this intriguing research.”