Sophie Breton, Professor in the Department of Biological Sciences and holder of the Canada Research Chair in the Evolutionary Biology of Mitochondria
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Mitochondrial DNA and its “small” number of base pairs (about 16,000, which is significantly less than nuclear DNA, which contains more than 3 billion) was sequenced almost 45 years ago. “The sequencing of the mitochondrial DNA was done quickly. “The scientific community had certainly understood everything about this tiny genetic material,” says Sophie Breton, professor in the Department of Biological Sciences and holder of the Canada Research Chair in the Evolutionary Biology of Mitochondria.
However, the professor had an intuition. There may be other genes hiding there. In fact, mitochondria are the result of the evolution of a number of bacteria, which in turn possess genes hidden within other genes. “Does the mitochondrial genome still have this property?” Ms. Breton wondered. She and her team have managed to prove that. Their discovery was published in the journal BMC Biology in mid-May. “We found a gene hidden inside another gene. “The DNA of the mitochondria is like a game with Russian dolls,” she compares.
From mollusks to humans
It is colossal work that has led to this discovery. The person who discovered new mitochondrial genes in mussels during her postdoctoral research in 2009 wondered if there wasn’t something on the human side too. “The mitochondrial DNA of molluscs is about as long as that of humans. It is plausible that we missed something,” explains Ms. Breton. But without a background in health research, “it was a bit more difficult to convince peers and get funding,” she says.
After receiving a professorship at the University of Montreal in 2012, she received grants to support her various work. “I received no funding for this research; I took risks and scratched the bottom of my drawer,” she notes. But thanks in part to her research chair, she was able to raise the necessary funds to test her hypothesis.
As of 2018, Sophie Breton and her colleagues Xavier Roucou from the Université de Sherbrooke, Christian Landry from the Université Laval and Annie Angers from the UdeM, and a team of students (Laura Kienzle, Stefano Bettinazzi and Thierry Choquette) have carried out laboratory research on the subject . “There were a lot of biochemical, physiological, microscopic and bioinformatic analyses. We haven’t used tools like CRISPR yet, but it might be interesting to do so one day to see what happens if we prevent hidden genes from expressing themselves,” suggests Ms Breton. In fact, they are hidden genes, as the team revealed the existence of a second hidden gene, which will be the subject of another publication later this year.
A shocking discovery
The discovery by Ms Breton and her team challenges several certainties. “Basically, we will have to rethink certain things,” she says. In addition, the reactions to his article are crucial. “We are shaking the foundations a bit. We are praised and criticized on Twitter!”
This discovery opens the door to direct applications to better understand and treat certain diseases such as diabetes, Parkinson’s and Alzheimer’s or certain cancers related to mitochondria. In some cases, scientists did not understand the links between a synonymous or silent mutation, meaning a mutation that does not change the protein, and a disease. “But it may be that the mutation does not take place silently in the hidden gene, but changes the protein, which could explain some of these puzzling observations,” she continues. To better understand these hidden genes, other potential therapeutic targets need to be explored to better treat or cure these diseases.
Sophie Breton hopes to continue research in this area in collaboration with colleagues from different disciplines. She has also applied for fellowships with the Canadian Institutes of Health Research (CIHR). “We want to better identify the functions of the gene that we just discovered,” she says.
Real power packs
Mitochondrial DNA is the DNA contained in the mitochondria, which are true energy centers for cells. “These power plants have a very small DNA. It’s an additional genetic element to our core’s DNA,” summarizes Ms. Breton. Mitochondrial DNA, which consists of just 37 genes, is passed down from our mothers and encodes key elements in the mitochondria needed for energy production.