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Key points
- Inheritance promotes psychological illness, but the specific genes responsible are elusive.
- A study shows alterations in DNA between genes can promote schizophrenia, depression, and bipolar disorder.
- Prehistoric viral infection altered DNA in ways that promote many mental illnesses.
People understand that someone can be predisposed to mental illness by inheriting certain genes or gene variants, but new research is revealing that inherited mental illnesses are also promoted by alterations in our DNA that were caused by viral infection of our ancestors over a million years ago. Remarkably, the changes do not modify parts of DNA coding genes, but instead parts that were once called ‘junk DNA,’ which control how genes are expressed.
Physical and mental illnesses, like most things in biology, are a consequence of genes, environment, and chance. Take schizophrenia for example. Certain life experiences and exposure to drugs including marijuana for some people, can increase the odds of developing the disorder, but 80% of the risk of developing this severe mental illness is genetic. If your identical twin has the disorder, there is a 50/50 chance that you will too. Yet research has failed to find a gene or gene mutation that causes schizophrenia. That conundrum probably means that the disorder results from complex interactions among many genes, but now scientists are recognizing a new explanation—they were looking in the wrong place in our DNA.
Genes are stretches of DNA that make all the proteins that build and run our bodies. Each gene is like a pearl on a necklace. While scientists first focused their search for the genetic basis for mental illnesses on genes (the pearls), they neglected the strands of DNA between them. Those stretches of DNA between genes control how a gene is activated or suppressed. If those inter-gene strands of DNA get fouled up, the genes that are vital for the brain and body to function normally will not operate properly, even though there may be nothing wrong with the genes themselves.
If alterations in stretches of DNA between genes are the culprit in inherited mental illness, the question then becomes, how does the DNA between genes get fouled 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 finds that viral infections in ancient times explain how many mental illnesses are inherited.
How DNA Works
To understand this new research, a brief refresher on the basics of how DNA works will be helpful. DNA is a genetic code, much like software code that runs computers, but rather than information being coded in zeros and ones, information in DNA is coded in four types of molecules. Just as the sequence of zeros and ones specifies software instructions, the sequence of four molecules on a string of DNA encodes all the information required to build and run every cell in our body.
The genetic instructions in DNA are the master ‘blueprint’ for making all the proteins in the body, and this vital code remains inside the cell’s nucleus. When a gene is turned on to make the protein it specifies, another molecule, RNA, makes a temporary copy of the gene and carries it out of the nucleus into the cell’s cytoplasm where specialized structures translate that RNA code to synthesize the protein specified by the gene. RNA self-destructs quickly so that old instructions do not bog down the operation, while the master code for genes is preserved in DNA and passed down to our offspring in egg and sperm cells. The one-way flow of genetic information from DNA to RNA to protein is called the ‘Central Dogma’ in biology, but retroviruses reverse-engineer the process 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 with the codes to make viral proteins into the cells they infect. That RNA can be converted into DNA and inserted into the host’s DNA. Then, like malicious code slipped into software by a computer hacker, the viral gene gets read out when the infected cell runs its genetic operation converting DNA into RNA and into a protein, unwittingly making new virus.
Sometimes, fragments of viral RNA get inserted into the host’s DNA and remain there. The fragment does not make a protein, but when it is inserted between genes, it can affect how genes are read out. This can cause serious inherited disorders, but it can also result in quantum leaps in evolution, by suddenly generating new traits in the line of inheritance without the usual gradual mutation and natural selection that drives evolution. A recently discovered example is the sudden appearance of the vital electrical sheath on nerve fibers, called myelin, which transformed how information is transmitted in the brain and body. Myelin appeared suddenly in animals with backbones (vertebrates), and according to new research, viral infection in ancestors of vertebrates sparked that sudden advance.
Splicing RNA to Make Hundreds of Variations
But there is more involved in the central dogma than you likely learned in biology class. If the “one gene-one protein” rule was correct, the human body would have only about 20,000 proteins, but the fact is that one gene can make up to 100 different types of proteins. One reason for this is that the RNA made from the gene coded in DNA can become spliced in various ways. Much like a gardener can splice three varieties of apples onto one tree and create an entirely new plant, RNA splicing generates multiple variations of a protein.
Ancient Virus Infection Promotes the Inheritance of Brain Disorders
Knowing about retroviruses, you no doubt already surmised how viral infection could foul up RNA editing and produce protein variations that could contribute to mental illness. If viral RNA fragments get inserted into DNA, which is inherited, when the cell reads out its DNA and makes these viral RNA fragments, they can change the process of splicing RNA and generate aberrant proteins. That’s what the latest research has found to be a major reason for some inherited neurodevelopmental intellectual disabilities.
In the new study on virus and inherited psychological illness, researchers analyzed RNA from 792 postmortem brain samples and identified 1,238 RNA fragments that originated from a virus. Twenty-six of these were associated with psychiatric disorders. Two were specific to the risk of schizophrenia. One of these was also associated with the risk of both schizophrenia and bipolar disorder, and another one was associated specifically with major depressive disorder.
As understanding of the complex mechanisms of genetics increases, understanding of how complex psychological and neurological disorders are inherited is increasing. These new findings offer new hope for treatment and remind us again of how integrated our bodies are in the complex fabric of life on Earth.
