Out of the 3 billion base pairs in the human genome, only about 2% actually codes for protein. Hidden in the vast sequences of non-coding DNA responsible for genetic regulation are retroviruses that we have picked up throughout our evolutionary history. Viruses are usually equated with disease, that is not always the case.
A new study provides evidence that some retroviral DNA became integrated in the regions of the genome that influence regulation of genes in the brain, manipulating the cells’ basic function. This could help explain why brain cells are able to have so many different roles, and could even influence our intelligence or our susceptibility to disease. The research team was headed by Johan Jakobsson of Lund University in Sweden, and the open access paper was published in Cell Reports.
Roughly 5% of our DNA is believed to be attributed to these retroviruses; most of which has been integrated into non-coding DNA. Jakobsson’s team found that some endogenous retroviruses (ERVs) have become integrated into the regions responsible for regulating transcription of neural progenitor cells (NPCs). NPCs are sort of like stem cells, except they are only able to differentiate into different kinds of neurons. These ancient genetic stowaways are believed to actually play a role in regulating the function of genes in the brain.
"We have been able to observe that these viruses are activated specifically in the brain cells and have an important regulatory role,” Jakobsson said in a press release. “We believe that the role of retroviruses can contribute to explaining why brain cells in particular are so dynamic and multifaceted in their function. It may also be the case that the viruses' more or less complex functions in various species can help us to understand why we are so different.”
The corepressor TRIM28 is a master regulator of ERVs as well as all other retroelements. Eliminating Trim28 in mice resulted in increased transcription of ERVs, which then began to affect expression of proximal genes. Targeting other ERV regulators could yield new information about how specific ancient hitchhikers influence genes in the brain, and what could potentially lead to their dysfunction. Understanding the full effect that ERVs have on brain functions could have widespread implications for diseases with a genetic component.
"I believe that this can lead to new, exciting studies on the diseases of the brain. Currently, when we look for genetic factors linked to various diseases, we usually look for the genes we are familiar with, which make up a mere two per cent of the genome,” Jakobsson explained.
“Now we are opening up the possibility of looking at a much larger part of the genetic material which was previously considered unimportant. The image of the brain becomes more complex, but the area in which to search for errors linked to diseases with a genetic component, such as neurodegenerative diseases, psychiatric illness and brain tumors, also increases.”