A new way to evolve? Mitochondrial DNA is inserted into our genome

Researchers at the University of Cambridge and Queen Mary University of London have shown that mitochondrial DNA also appears in some cancer DNA, suggesting that it acts like a Band-Aid, trying to repair damage
to our genetic code.
The findings were published in the journal Nature on October 5
.

Mitochondria are tiny organelles within a cell that, like batteries, provide energy
to cells in the form of ATP molecules.
Each mitochondria have their own DNA, known as mitochondrial DNA, which is very different
from the rest of the human genome (nuclear DNA).

Mitochondrial DNA is inherited through matrilineal lines—that is, we inherit it
from our mother, not our father.
However, a 2018 study published by researchers at Cincinnati Children's Hospital Medical Center in the United States reported that there is evidence that some mitochondrial DNA is inherited through paternal lines
.

To investigate this claim, the Cambridge University team studied the DNA of more than 11,000 families that are involved in Genomics England's 100,000 Genome Project
.

The researchers found mitochondrial DNA "inserts" in the nuclei DNA of some children that were not present in their parents' DNA
.
This means that the U.
S.
team may have come to the wrong conclusion: What they observed was not paternal-inherited mitochondrial DNA, but these inserts
.

Now, the work has expanded to more than 66,000 people
.
The research team showed that mitochondrial DNA nuclear transfer is an ongoing process and that new insertions actually happen all the time, showing a new way
our genome evolved.

Professor Patrick Chinnery, from the Department of Clinical Neuroscience at the University of Cambridge, explains: "Billions of years ago, primitive animal cells absorbed a bacterium that became what we now call mitochondria
.
They provide energy to the cells to make them work properly while removing high concentrations of oxygen
.
Over time, a portion of these primitive mitochondria have entered the nucleus, allowing their genomes to communicate with
each other.

"All of this was thought to have happened a long time ago, mostly before speciation, but we found that this is not true
.
We can see this happening, with the genetic code of mitochondria being transferred to the nuclear genome in a measurable way," he said
.

The research team estimates that one in every 4,000 newborns has mitochondrial DNA transferred to nuclear DNA
.
If the person has children of their own, they pass on these inserts
.
The team found that most of us carried 5 new inserts, and one in seven (14%) carried the latest inserts
.
By chance, these inserts can cause extremely rare diseases, including rare hereditary cancers
.

It's unclear how mitochondrial DNA is inserted into the nucleus DNA — either directly or through intermediates (such as RNA) — but Professor Chinnery says this is likely to happen inside
the mother's egg cells.

After analyzing the sequences of 12,500 tumor samples, the researchers found that mitochondrial DNA is more common in tumor DNA, with mitochondrial DNA appearing in about one in every 1,000 cancers, and in some cases, cancers are actually caused
by mitochondrial DNA inserts.

"Our nuclear genetic code has been broken and has been repaired," Professor Chinnery said
.
"Mitochondrial DNA seems like a band-aid that helps the genetic code of the nucleus repair
itself.
Sometimes this approach works, but in rare cases, it can make the situation worse and even cause tumorigenesis
.
”

More than half (58%) of the inserts are located in the genomic region
that codes for the protein.
In most cases, the body recognizes invading mitochondrial DNA and silences
it through the process of methylation.
A similar process occurs when a virus manages to insert itself into our DNA
.
However, this method of silencing is not perfect, as some mitochondrial DNA inserts continue to be replicated and move
around the nucleus.

The team was also looking for evidence of the opposite, that is, mitochondrial DNA absorbs a portion of the nuclear DNA, but they did not find it
.
They believe that the following reasons may explain why this is the case
.

First, cells have only two copies of nuclear DNA, but mitochondrial DNA has thousands of copies, so the possibility of mitochondrial DNA being destroyed and entering the nucleus is much greater
.
Second, the DNA in the mitochondria is wrapped within two layers of membranes with no pores in the membrane, so nuclear DNA is difficult to enter
.
In contrast, once mitochondrial DNA successfully runs out, they easily pass through holes in the nuclear membrane
.

Professor Mark Caulfield, from Queen Mary University of London, said: "I am delighted that the 100,000 Genomes Project has uncovered the dynamic interactions between mitochondrial DNA and our genomes
.
This defines a new role in DNA repair, but occasionally triggers rare diseases and even malignancies
.
”

Source text search

Wei, W.
, Schon, K.
R.
, Elgar, G.
et al.
Nuclear-embedded mitochondrial DNA sequences in 66,083 human genomes.
Nature (2022).
https://doi.
org/10.
1038/s41586-022-05288-7