Less separated than thought: A study shows that pieces of the normally separate genome of our cellular power plants can sometimes be incorporated into the nuclear DNA. Such a transfer of mitochondrial sequences occurs in the genesis of about 1 in 4000 people. The effect could have evolutionary significance and there is also evidence of a connection with cancer, say the scientists.
Similar to the entire body, its cells also have functional units - the so-called organelles. The mitochondria have a power plant function: they provide energy in the form of the molecule ATP for the operation of the cells. These organelles are also characterized by another special feature: each mitochondrion has its own DNA, which differs from the rest of the human genome, which consists of nuclear DNA. The mitochondrial DNA includes genes that serve the function of the organelle.
On the trail of integrated mitochondrial DNA
It is assumed that the system arose in ancient times through the process of what is known as endosymbiosis: at some point a unicellular organism absorbed another microbe and a unit was finally formed. The mitochondria therefore still have characteristics of a separate organism – including their own genome. It was already known that DNA transfer from the mitochondria to the cell nucleus once occurred. However, it was previously assumed that the corresponding nuclear mitochondrial segments are ancient and long preceded human evolutionary history.
Another special aspect is that mitochondrial DNA is only inherited through the maternal line - that is, we do not inherit it from our fathers. In 2018, however, a research team came across an astonishing finding: their results seemed to suggest that part of the mitochondrial DNA can also be inherited in the paternal line. A research team led by Patrick Chinnery from the University of Cambridge followed this lead. In doing so, the scientists came across the first indications that there may be mitochondrial DNA inserts in the nuclear DNA of children that were not present in the DNA of their parents.
What the researchers had previously observed were therefore probably not paternally inherited mitochondrial units, but these genetic insertions. To shed more light on this phenomenon, Chinnery and his colleagues have now conducted a broader study: They searched the genome sequences of 66,000 people for traces of mitochondrial DNA segments that were relatively late in entering the nuclear DNA. As they explain, this assignment is possible based on certain genetic characteristics of the pieces.
Continuous installation
As the team reports, their analyzes revealed that there is still a transfer of mitochondrial DNA into the cell nucleus. "This was thought to have happened a long time ago, before we evolved as a species, but we discovered that wasn't the case," says Chinnery. The team found that most of us carry around five new insertions, and one in seven carries a particularly young one. More than 90 percent of the 1,637 distinct pieces discovered were inserted into the nuclear genome after humans split off from apes, the researchers write. The team estimates that transfer of mitochondrial sequences into nuclear DNA occurs in the genesis of about 1 in 4,000 people.
It's not exactly clear how the mitochondrial DNA snippets insert - whether directly or via an RNA intermediate. But the process probably occurs in the mother's eggs, the researchers say. According to them, the reason why pieces of mitochondrial DNA do not increasingly accumulate in the human genome is that they disappear from the genome again particularly frequently. The incorporation of the sequences often remains largely without consequences, but occasionally the genetic changes could also lead to various effects on the organism. The scientists say that the ongoing integration of mitochondrial genome pieces into the nuclear DNA could have had an impact on human evolution.
As they continue to report, their results also provided interesting indications of a possible connection between the DNA insertions and cancer: When the researchers examined genetic sequences from 12,500 tumor samples, they found that mitochondrial DNA is found comparatively frequently in tumor DNA: in about one in 1000 cancer cases. In some cases, the insertion could also have caused the cancer. However, mitochondrial DNA may also have a positive function: "Our nuclear genetic code is constantly being broken and repaired," explains Chinnery. "The mitochondrial DNA could act like a band-aid that helps to repair the genetic core code. Sometimes that might work, but in rare cases it can make things worse or even trigger tumors to develop," Chinnery said.
It seems that the study now raises interesting further questions.
Source: University of Cambridge, professional article: Nature, doi: 10.1038/s41586-022-05288-7