Mysterious Viral DNA in Human Genome Linked With Psychiatric Disorders : ScienceAlert

About 8% of human DNA is made up of genetic sequences acquired from ancient viruses. These sequences, known as human endogenous retroviruses (or Hervs), date back hundreds of thousands or even millions of years, with some even predating the emergence of Homo sapiens.

Our latest research suggests that certain 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 by ancient retroviruses. Retroviruses are viruses that insert a copy of their genetic material into the DNA of the cells they infect.

Retroviruses have probably infected us several times during our past evolution. When these infections occurred in the sperm or eggs that generated offspring, the genetic material from these retroviruses was passed on to subsequent generations, becoming a permanent part of our lineage.

Initially, scientists considered Hervs to be “junk DNA” – parts of our genome with no discernible function. But as our understanding of the human genome advances, it is becoming clear that this junk DNA is responsible for more functions than initially assumed.

First, the researchers discovered that Hervs could regulate the expression of other human genes. A genetic trait is said to be “expressed” if its DNA segment is used to produce RNA (ribonucleic acid) molecules.

These RNA molecules can then serve as intermediates leading to the production of specific proteins, or help regulate other parts of the genome.

Early research suggests that Hervs regulate the expression of neighboring genes with important biological functions. One example is a Herv that regulates the expression of a gene involved in changing connections between brain cells.

Hervs have also been found to produce RNA and even proteins in blood and brain samples. These molecules have the potential to exert a wide range of functions, as they can cross cellular compartments to fulfill different roles.

Scientists have also found evidence suggesting that some human genes derive from Hervs. This indicates that there have been instances during evolution where Hervs have been co-opted for specialized biological functions.

For example, the human syncytin 1 and 2 genes, derived from Herv, play a central role 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 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 influenced Herv expression in the brain.

We then cross-referenced this information with the results of large genetic studies that had compared the genetic differences between tens of thousands of people – with or without mental health problems. These studies identified DNA variations associated with different psychiatric conditions.

We found that the expression of four Hervs was linked to genetic susceptibility to major psychiatric disorders. Expression of two of these Hervs was associated with schizophrenia, one Herv with both schizophrenia and bipolar disorder, and one with depression.

These results suggest that Hervs may play a more important role in the brain than initially thought.

Many genes are involved in psychiatric disorders – and Herv genes are only part of this puzzle. Although the precise impact of these Hervs on brain cells and on a person’s susceptibility to certain psychiatric disorders requires further research, our study is the first to show that genetic susceptibility to a psychiatric disorder also acts through the via these ancient viral DNA sequences.

It is still too early to determine the practical applications 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 recognizes the importance of these mysterious sequences in the human genome, which have been ignored for years.

Rodrigo Duarte, researcher at King’s College London; Douglas Nixon, Professor of Immunology in Medicine, Cornell University, and Timothy Powell, Senior Lecturer, King’s College London

This article is republished from The Conversation under a Creative Commons license. Read the original article.

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