by About 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 – with some even predating evolution. 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 the 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 plagued us many times throughout our evolutionary history. When these infections occurred in sperm or egg cells that produced the offspring, the genetic material from those retroviruses was passed on to subsequent generations, becoming a permanent part of our lineage.
At first, scientists considered Hervs to be “junk DNA” – parts of our genome with no discernible function. But as our understanding of the human genome has evolved, it has become clear that the so-called junk DNA is responsible for more functions than originally hypothesized.
First, the researchers discovered that Hervs can regulate the expression of other human genes. A genetic element is said to be “expressed” if its DNA segment is used to produce RNA (ribonucleic acid) molecules. These RNA molecules can act as mediators leading to the production of specific proteins, or help regulate other parts of the genome.
Initial research suggested that Hervs regulate the expression of neighboring genes with important biological functions. One example of this is Herv which regulates gene expression involved in modulating connections between brain cells.
Hervs have also been found to produce RNAs and even proteins in blood and brain samples. These molecules have the ability to perform a wide range of functions, as they can travel across cellular compartments to perform different roles.
Scientists have also found evidence that suggests that certain human genes are derived from Hervs. This indicates that there have been instances during evolution where Hervs have been co-opted for specific biological functions. For example, the human genes syncytins 1 and 2, which are derived from Hervs, play central roles in placental development.
HERVs in psychiatric disorders
Given the abundance of Hervs in the genome and their potential multiple functions, we wanted to better understand whether genetic susceptibility to certain psychiatric disorders was associated with differences in Herv expression.
In our study, we profiled Herv expression in nearly 800 autopsy brain samples. This helped us identify DNA variations that affected Herv expression in the brain.
We then cross-referenced this information with results from large genetic studies comparing genetic differences between thousands of people – with and without mental health conditions. These studies have identified variations in DNA associated with various psychiatric conditions.
We found that expression of four Hervs was associated with genetic susceptibility to major psychiatric disorders. The expression of two of these Hervs was associated with schizophrenia, one Herv with schizophrenia and bipolar disorder, and another with depression. These findings suggest that Hervs may play a more important role in the brain than originally thought.
Read more: Discovering how genetic ‘dark matter’ plays a role in mental illness is just the tip of the iceberg for human health
There are many genes involved in psychiatric disorders – and the Hervs are just part of the puzzle. Although more research is needed on the exact impact of these Hervs on brain cells and a person’s susceptibility to certain psychiatric disorders, our study is the first to show that genetic susceptibility to a psychiatric disorder acts through the DNA sequences this ancient viral too.
It is still too early to determine the practical application of our findings – and whether they could 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 identifies the importance of these mysterious sequences in the human genome, which have been overlooked for many years.
This article from The Conversation is republished under a Creative Commons license. Read the original article.
Rodrigo Duarte received funding from the National Institutes of Health, USA.
Douglas Nixon receives funding from the National Institutes of Health, USA.
Timothy Powell receives funding from the National Institute for Health and Care Research, the National Institutes of Health, and the Medical Research Council.
