Scientists have found that in one out of every 4,000 births, some of the genetic material from our mitochondria, the “batteries” that power our cells, gets inserted into our DNA. This is a shocking new way to think about how humans have changed over time. Researchers from Queen Mary University of London and the University of Cambridge demonstrate that mitochondrial DNA can also be found in some cancer DNA in a study that was just published in Nature. This finding makes it more likely that mitochondrial DNA is a short-term fix for broken genetic code.
The tiny “organelles” known as mitochondria are found inside our cells, where they function as batteries, supplying the cells with energy in the form of the molecule ATP. The mitochondrial DNA that makes up each mitochondrion is unique from the nuclear DNA that makes up the rest of the human genome.
We inherit our mitochondrial DNA from our mothers, not from our fathers, because it is passed down the maternal line. However, a study from Cincinnati Children’s Hospital Medical Center researchers that was published in PNAS in 2018 provided evidence that suggested some mitochondrial DNA had been passed down the paternal line.
The Cambridge team examined the DNA of more than 11,000 families enlisted in Genomics England’s 100,000 Genomes Project in an effort to verify these claims. They looked for patterns that suggested paternal inheritance. The Cambridge team discovered mitochondrial DNA “inserts” in some children’s nuclear DNA that weren’t present in their parents’ nuclear DNA. This meant that the US team probably came to the wrong conclusions because what they had seen was these inserts and not mitochondrial DNA from the father.
By looking at more than 66,000 people, the team has shown that the new inserts are actually happening all the time. This shows a new way that genomes change over time.
A primitive animal cell ingested a bacterium that evolved into what we now refer to as mitochondria billions of years ago, according to Professor Patrick Chinnery of the Medical Research Council Mitochondrial Biology Unit and the Department of Clinical Neurosciences at the University of Cambridge. These give the cell the energy it needs to function normally while also removing oxygen, which can be toxic in large doses. Over time, parts of these old mitochondria have moved into the cell nucleus, allowing their genomes to talk to each other.
The majority of this was thought to have occurred before our species had even begun to form, but we’ve found that’s not the case. With quantifiable transfers of our mitochondrial genetic code into the nuclear genome, we can see this happening right now.
The researchers calculate that one in every 4,000 births results in the transfer of mitochondrial DNA to nuclear DNA. The team discovered that the majority of us carry five new inserts, and one in seven of us (14%) carries very recent ones. If that person has children of their own, they will pass these inserts on to them. Once they are put in, the inserts can sometimes cause very rare diseases, like a rare genetic form of cancer.
Professor Chinnery thinks that the most likely place where mitochondrial DNA is put in is in the egg cells of the mother. It is not known if this happens directly or through something like RNA.
When the team looked at the sequences of 12,500 tumor samples, they found that mitochondrial DNA was even more common in tumor DNA. It was found in about 1 in 1,000 cancers, and in some cases, the cancer was caused by the mitochondrial DNA inserts.
According to Professor Chinnery, “our nuclear genetic code is breaking and being repaired constantly.” The nuclear genetic code appears to be able to repair itself with the assistance of mitochondrial DNA, almost like a Band-Aid or plaster. And, while this occasionally works, it can also make things worse or even cause tumors to form.
More than half (58%) of the insertions occurred in the regions of the genome that code for proteins. The majority of the time, a molecule attaches to the insert and turns off the insert as soon as the body recognizes the invasive mitochondrial DNA. This process is known as methylation. A similar process takes place when viruses are able to insert themselves into our DNA. This method of silencing is imperfect, though, because some mitochondrial DNA insertions copy themselves and move within the nucleus.
The team searched for proof that the opposite might occur—that our nuclear DNA might be partially absorbed by our mitochondria—but they came up empty-handed. There are probably a number of explanations for why this is the case.
First off, cells only have two copies of nuclear DNA, whereas there are thousands of copies of mitochondrial DNA. As a result, there is a much greater chance that mitochondrial DNA will break and enter the nucleus than the reverse.
Furthermore, there are no holes in the two membranes that contain the mitochondrial DNA, making it difficult for nuclear DNA to enter. Nuclear DNA, on the other hand, would pass through holes in the membrane surrounding it relatively easily if mitochondrial DNA managed to escape.
The 100,000 Genomes Project has revealed the dynamic interaction between our genome and mitochondrial DNA in the cell’s nucleus, said Professor Sir Mark Caulfield, Vice Principal for Health at Queen Mary University of London. The definition of a new role in DNA repair makes it possible that this role could sometimes cause rare diseases or even cancer.
Most of the money for the study came from the Medical Research Council, Wellcome, and the National Institute for Health Research.
