Ancient Viral DNA May Shape Susceptibility to Psychiatric Disorders

Around 8% of human DNA consists of genetic sequences inherited from ancient viruses. Known as human endogenous retroviruses (HERVs), these sequences date from hundreds of thousands to millions of years ago, and some existed even before Homo sapiens emerged.

Our recent research indicates that certain ancient viral DNA sequences within the human genome may influence vulnerability to psychiatric conditions, including schizophrenia, bipolar disorder and major depressive disorder.

HERVs are the surviving traces of infections caused by ancient retroviruses. Retroviruses are viruses that place a copy of their genetic material into the DNA of the cells they infect.

Over the course of human evolution, retroviruses are likely to have infected our ancestors repeatedly. If an infection affected sperm or egg cells that went on to produce offspring, the retrovirus's genetic material could be inherited by later generations and become a lasting element of our lineage.

Scientists originally regarded HERVs as "junk DNA" – sections of the genome with no apparent purpose. However, growing knowledge of the human genome has shown that this supposedly useless DNA carries out more roles than was first assumed.

How HERVs influence the human genome

Researchers initially discovered that HERVs can control the expression of other human genes. A genetic feature is described as being "expressed" when its DNA sequence is used to create RNA (ribonucleic acid) molecules.

Those RNA molecules may act as intermediaries in producing particular proteins, or they can assist in regulating other areas of the genome.

Early studies indicated that HERVs regulate the expression of nearby genes with significant biological roles. For instance, one HERV controls the expression of a gene involved in altering the connections between brain cells.

HERVs have also been shown to generate RNAs, and even proteins, in blood and brain samples. As these molecules can move between cellular compartments to perform different tasks, they could potentially have a broad range of functions.

Scientists have additionally identified evidence that some human genes originated from HERVs. This suggests that, at points in evolution, HERVs were recruited for specialised biological purposes.

For example, the human genes syncytins 1 and 2, which originated from HERVs, have crucial roles in the development of the placenta.

HERVs in psychiatric disorders

Given the large number of HERVs in the genome and their potentially extensive range of functions, we sought to establish whether genetic vulnerability to particular psychiatric disorders was connected to variation in HERV expression.

For our study, we mapped HERV expression in almost 800 post-mortem brain samples. This allowed us to identify DNA variations that affected how HERVs are expressed in the brain.

We then compared these data with results from major genetic studies that examined DNA differences in tens of thousands of people, including people with and without mental health conditions. Those studies had identified DNA variations linked with distinct psychiatric disorders.

We discovered that the expression of four HERVs was associated with genetic susceptibility to major psychiatric disorders. Two of these HERVs were linked to schizophrenia, one was associated with both schizophrenia and bipolar disorder, and one was linked with depression.

The findings indicate that HERVs could have a more substantial role in the brain than was previously recognised.

Ancient viral DNA and genetic susceptibility

Psychiatric disorders involve many genes, and HERVs represent only one part of this complex picture. More research is needed to establish the exact effects of these HERVs on brain cells and on a person's vulnerability to specific psychiatric disorders. Nevertheless, our study is the first to demonstrate that genetic susceptibility to a psychiatric disorder can also operate through these ancient viral DNA sequences.

It remains too soon to know how our findings could be applied in practice, including whether they could contribute to the development of new treatments. However, we are optimistic about this avenue of research.

By connecting HERV expression in the brain to psychiatric disorders, our research highlights the significance of these enigmatic sequences in the human genome, which have been overlooked for years.

Rodrigo Duarte, Research Fellow, 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 licence. Read the original article.