Science & Technology, Canada (Commonwealth Union) – Mitochondrial DNA, which comprises a relatively small number of base pairs (approximately 16,000 compared to the 3 billion in nuclear DNA), was initially sequenced nearly 45 years ago. Sophie Breton, a professor at the University of Montreal’s (UdeM), Department of Biological Sciences and the Canada Research Chair in Evolutionary Mitochondrial Biology, indicated that once mitochondrial DNA was sequenced, it was believed that the scientists had exhausted its secrets, given its diminutive size in the genetic landscape.
However, Breton, intrigued by the fact that mitochondria have bacterial origins, and bacteria possess genes nested within other genes, harbored a suspicion that there might be concealed genes within mitochondrial DNA. She pondered, “Could the mitochondrial genome still retain such a characteristic?” Subsequently, her team’s research confirmed that, it does for sure.
Their discoveries were unveiled in a mid-May publication in BMC Biology.
Breton indicated that they unearthed a gene concealed within another gene, further elaborating that inn essence, mitochondrial DNA can be likened to a series of nested Russian dolls.
The journey towards this discovery involved an enormous amount of effort and dedication. Sophie Breton’s initial encounter with novel mitochondrial genes in mussels during her postdoctoral work planted the seed of curiosity back in 2009. She couldn’t help but wonder whether a similar phenomenon existed in humans. As she pointed out, that the length of mitochondrial DNA in mollusks is comparable to that in humans, raising the possibility that we might have overlooked something. However, her lack of training in health research made it challenging to persuade colleagues and secure funding.
Years passed, and in 2012, Breton became a professor at UdeM, eventually obtaining funding for her research. Partly owing to her Chair’s support, she managed to gather the necessary resources to test her hypothesis. Reflecting on this period, she recollected, that she didn’t receive any external funding for this study and took risks and made do.
In 2018, Breton, along with her colleagues Xavier Roucou, Christian Landry, and Annie Angers from Université de Sherbrooke, Université Laval, and Université de Montréal, respectively, collaborated with students Laura Kienzle, Stefano Bettinazzi, and Thierry Choquette to commence the investigation in the laboratory. This endeavor demanded extensive work in biochemistry, physiology, microscopy, and bioinformatics analysis. Breton noted, that they didn’t utilize tools like CRISPR, but it might be intriguing to explore in the future to observe the effects when they inhibit the expression of these concealed genes. Notably, their research unveiled not one but multiple hidden genes, with a second nested gene awaiting exploration in a forthcoming article later in 2023.
The key finding made by Breton together with her team challenges what was regarded as fact in the field. “Some things about the basic science will have to be rethought,” she said. Her article has bought about robust reactions from both sides. “We’ve upset the apple cart. We’re being praised and bashed on Twitter.”
The discovery carries significant practical implications, particularly in its potential direct application to the comprehension and treatment of certain diseases. Several diseases, including diabetes, Parkinson’s, Alzheimer’s, and certain cancers, have established connections with mitochondria. In some instances, the link between a synonymous mutation (an alteration in a DNA sequence that does not visibly modify the protein) and a disease remains unclear.
“However, it’s conceivable that the mutation may not remain inconspicuous within the concealed gene, potentially altering the protein. This could provide an explanation for some of the perplexing observations,” suggested Breton. A deeper understanding of these nested genes may pave the way for identifying additional therapeutic targets, ultimately enhancing the effectiveness of disease treatments, and possibly even leading to cures.
Breton had stated her desire to carry on with research along with the other researchers of the study from various disciplines.
