Viral infections can alter DNA and promote inherited mental illnesses

Source: Credit: NIAID, public domain

It is well known that people can be susceptible to mental illness by inheriting certain genes or gene variants. However, new research shows that inherited mental illness is also due to changes in our DNA caused by viral infections in our ancestors over a million years ago. Remarkably, these changes do not alter parts of DNA-coding genes, but rather parts previously called “junk DNA” that control the expression of genes.

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Physical and mental illnesses, like most things in biology, are a result of genes, environment and chance. Take schizophrenia, for example. Certain life experiences and exposure to drugs, including marijuana, can make some people more likely to develop the disease, but 80% of the risk of developing this serious mental illness is genetic. If your identical twin has the disease, there's a 50/50 chance you will, too. So far, research has not been able to find a gene or gene mutation that causes schizophrenia. This mystery likely means the disease is the result of complex interactions between many genes, but now scientists are seeing a new explanation—they've been looking in the wrong place in our DNA.

Genes are stretches of DNA that make up all the proteins that build and control our bodies. Each gene is like a pearl on a necklace. While scientists initially focused their search for the genetic basis of mental illness on genes (the pearls), they neglected the strands of DNA between them. These stretches of DNA between genes control how a gene is activated or suppressed. When these strands of DNA between genes get messed up, the genes that are vital to the normal functioning of the brain and body don't work properly, even though there may be nothing wrong with the genes themselves.

If changes in DNA stretches between genes are the cause of inherited mental illness, the question is how the DNA between genes got mixed up. A new study provides a surprising answer. Certain viruses insert their genetic material into their host's DNA when they infect cells. New research shows that viral infections in ancient times explain how many mental illnesses are inherited.

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How DNA works

To understand this new research, a quick refresher on the basics of how DNA works is helpful. DNA is a genetic code, similar to the software code that runs computers, but instead of encoding information in zeros and ones, the information in DNA is encoded in four types of molecules. Just as the sequence of zeros and ones specifies software instructions, the sequence of four molecules on a DNA strand encodes all the information needed to build and run every cell in our bodies.

The genetic instructions in DNA are the master blueprint for making all proteins in the body, and this vital code remains in the cell nucleus. When a gene is activated to make the protein it specifies, another molecule, RNA, makes a temporary copy of the gene and transports it out of the nucleus into the cell's cytoplasm, where specialized structures translate this RNA code to synthesize the protein specified by the gene. RNA destroys itself quickly, so old instructions don't hinder the process, while the master code for genes remains in DNA and is passed on to our offspring in egg and sperm cells. The one-way flow of genetic information from DNA to RNA to protein is known in biology as the “Central Dogma,” but retroviruses engineer this process backwards when they infect cells.

How viruses change DNA

Viruses cannot make their own proteins. Instead, retroviruses like HIV, Covid-19 and others inject their RNA, containing the codes to make viral proteins, into the cells they infect. This RNA can be converted into DNA and inserted into the host's DNA. Then the viral gene is read out when the infected cell performs its genetic operation, converting DNA into RNA and into a protein, inadvertently creating a new virus.

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Sometimes fragments of viral RNA are inserted into the host's DNA and remain there. The fragment is not a protein, but when inserted between genes it can affect how genes are read. This can cause serious hereditary diseases, but it can also result in quantum leaps in evolution, suddenly creating new traits in the lineage without the usual gradual mutation and natural selection that drives evolution. One recently discovered example is the sudden appearance of the vital electrical sheath of nerve fibers, called myelin, which changed the way information is transmitted in the brain and body. Myelin appeared suddenly in animals with backbones (vertebrates), and new research suggests that a viral infection in vertebrate ancestors triggered this sudden advance.

Splicing of RNA creates hundreds of variations

But there's more to the central dogma than you probably learned in biology class. If the “one gene, one protein” rule were correct, the human body would have only about 20,000 proteins, but the fact is that one gene can produce up to 100 different types of protein. One reason for this is that the RNA made from the gene encoded in DNA can be spliced ​​in different ways. Just as a gardener can plant three kinds of apple on a tree and create an entirely new plant, RNA splicing creates multiple variants of a protein.

Infection with an ancient virus promotes the inheritance of brain diseases

If you know anything about retroviruses, you've probably guessed that a viral infection can mess up RNA editing and create protein variations that can contribute to mental illness. When viral RNA fragments are inserted into DNA (which is inherited), when the cell reads its DNA and makes these viral RNA fragments, they can alter the process of RNA splicing and create aberrant proteins. This is a major cause of some inherited neurodevelopmental disorders, according to recent research.

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In the new study on viruses and inherited mental illness, researchers analyzed RNA from 792 postmortem brain samples and identified 1,238 RNA fragments that came from a virus. Twenty-six of these were linked to mental disorders. Two of these were specifically linked to the risk of schizophrenia. One of these was also linked to the risk of both schizophrenia and bipolar disorder, and another was specifically linked to major depressive disorder.

As our understanding of the complex mechanisms of genetics increases, so does our understanding of the inheritance of complex psychological and neurological disorders. These new insights offer new hope for treatment and remind us once again how deeply our bodies are integrated into the complex fabric of life on Earth.