Your brain may be mutated in ways previously thought to be extremely rare

Mutations in which DNA from energy-producing mitochondria is mistakenly added to a cell’s main genome were thought to be extremely rare. Now, studies of brain tissue show that such mutations occur in all of us, and their numbers may be a factor in ageing.

“Not only are they present, but they’re abundant in the dorsolateral prefrontal cortex, an area of ​​the brain associated with cognitive abilities,” says Ryan Mills of the University of Michigan.

In human cells, almost all of the DNA (about 6 billion letters) resides in the nucleus, but the energy-producing organelles called mitochondria have their own tiny genome of about 16,600 letters.

That’s because mitochondria were once free-living bacteria with their own large genome. In the roughly 2 billion years since those bacteria formed a symbiotic relationship with our distant ancestors, most of the original bacterial genome has been lost or transferred to the main genome in the nucleus.

This evidence of transfer has meant that biologists have long known that pieces of mitochondrial DNA could somehow find their way into the nucleus and then be added to the main genome. But these kinds of mutations were thought to be very rare, Mills says. Over the past few years, work by his team and others has shown that, at least in cancer cells, this isn’t as uncommon as we thought.

Mills and his colleagues showed that these types of mutations also occur in non-cancerous cells by sequencing the DNA of brain tissue samples taken from 1,200 people during post-mortem examinations.

Although another team took the samples and sequenced them, Mills and his colleagues looked for mutations that add mitochondrial DNA to the nuclear genome. “We were just curious,” Mills says.

Not only did they find such mutations, but they also found that they were more prevalent in people who, on average, died younger.

It’s not clear whether these mutations are just a symptom of aging or a cause of it, Mills says. “The jury is still out,” he says. “But if you take the entire mitochondrial sequence and put it somewhere in the genome, it’s hard for me to believe that it wouldn’t have an effect.”