Approximately 8% of human DNA consists of genetic sequences obtained from ancient viruses. These sequences, known as human endogenous retroviruses (or Hervs), date back hundreds of thousands to millions of years, some even homo sapiens.
Our latest research suggests that some ancient viral DNA sequences in the human genome play a role in susceptibility to psychiatric disorders such as schizophrenia, bipolar disorder and major depressive disorder.
Hervs represent remnants of these infections with ancient retroviruses. Retroviruses are viruses that insert a copy of their genetic material into the DNA of the cells they infect. Retroviruses have likely infected us many times throughout our evolutionary history. When these infections occurred in the sperm or egg cells that created offspring, the genetic material from these retroviruses was passed on to subsequent generations, becoming a permanent part of our lineage.
Initially, scientists dismissed Hervs as “junk DNA,” parts of our genome that had no discernible function. But as our understanding of the human genome has improved, it has become clear that this so-called junk DNA is responsible for more functions than originally assumed.
First, researchers found that Hervs can regulate the expression of other human genes. A genetic trait is said to be “expressed” if the segment of DNA is used to produce RNA (ribonucleic acid) molecules. These RNA molecules can then serve as mediators that lead to the production of certain proteins or help regulate other parts of the genome.
Early studies suggested that Hervs regulates the expression of neighboring genes with important biological functions. One example of this is a Herv that regulates the expression of a gene involved in altering connections between brain cells.
Hervs have also been found to produce RNAs and even proteins in blood and brain samples. These molecules have the potential to exert a wide variety of functions as they can circulate between cellular compartments to fulfill different roles.
Scientists also found evidence that some human genes are derived from Hervs. This suggests that there are instances during evolution where Hervs have been selected for specific biological functions. For example, the Hervs-derived human genes syncytin 1 and 2 play crucial roles in placental development.
HERVs in psychiatric disorders
Given the abundance of Hervs in the genome and their potentially numerous functions, we wanted to better understand whether genetic susceptibility to certain psychiatric disorders is associated with differences in Herv expression.
In our study, we profiled Herv expression in approximately 800 autopsy brain samples. This helped us identify DNA variations that affect Herv expression in the brain.
We then cross-referenced this information with findings from large genetic studies that compared genetic differences between tens of thousands of people with and without mental health problems. These studies identified variations in DNA associated with different psychiatric conditions.
We found that expression of four Hervs was linked to genetic predisposition to major psychiatric disorders. Expression of two of these Hervs was associated with schizophrenia; one Herv was associated with both schizophrenia and bipolar disorder, and one Herv was associated with depression. These results suggest that Hervs may play a more important role in the brain than initially thought.
Read more: Discovering how genetic ‘dark matter’ plays a role in mental illness is just the tip of the iceberg for human health
Many genes are involved in psychiatric disorders, and Hervs are just one piece of the puzzle. Although the exact impact of these Hervs on brain cells and an individual’s susceptibility to certain psychiatric disorders requires further investigation, our study is the first to show that genetic susceptibility to a psychiatric disorder also acts through these ancient viral DNA sequences.
It is too early to determine the practical applications of our findings and whether they can be used to develop new treatments. But we are optimistic about this line of research. By linking Herv expression in the brain to psychiatric disorders, our research recognizes the importance of these mysterious sequences in the human genome that have been overlooked for years.
This article is republished from The Conversation under a Creative Commons license. Read the original article.
Rodrigo Duarte received funding from the US National Institutes of Health.
Douglas Nixon receives funding from the US National Institutes of Health.
Timothy Powell receives funding from the National Institute for Health and Nursing Research, the National Institutes of Health, and the Medical Research Council.