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Mitochondrial DNA is Making its Way Into the Human Genome

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This research shows that even after billions of years, the once independent, energy-producing bacterium may not have completed their role in endosymbiosis after all.

mitochondria cover pic

Billions of years ago, an important endosymbiotic event occurred in which an energy-producing bacterium was engulfed by a larger cell. Instead of being digested, the smaller bacterium and the cell formed a functional relationship in which the bacterium provides energy for the cell, with the two acting as one organism. This remarkable hijacking event marked the birth of the eukaryotic cell, the building block of all animals, plants, and fungi that exist today.

Mitochondrial Structure. Image: Flickr

1.45 billion years later, that once independent, energy-producing bacterium, mitochondria, is now famously known as the ‘powerhouse’ of the cell. These biological machines help to convert the food we eat into ATP, a chemical energy source we can use for our daily activities. Owing to their origin as an independent molecular entity, mitochondria have their own double membrane and mitochondrial DNA (mtDNA). This mtDNA is directly inherited from the mother and, by analysing mtDNA through generations, scientists have been able to gather significant ancestral data.

Until recently, it was generally accepted that after the initial re-localisation to the nucleus, mtDNA became genetically stationary, resembling ‘molecular fossils’ of the ancestral mitochondrial genome. However, new research published in Nature suggests that the mitochondrial genome is not so stationary after all. Patrick Chinnery, a neuroscientist at the University of Cambridge, and his colleges analysed fragments of mtDNA within the human genome of 66,083 individuals to investigate any unusual activity. Strikingly, they found that transfer of mitochondrial DNA to the nucleus is an ongoing process that still occurs today. The transfer of mitochondrial DNA into the nucleus was shown to occur once in every 4,000 births.

As these genomic changes are inherited by future generations, the ongoing insertion events play a role in the shaping of the human genome. Due to the dynamic nature of these insertion events, Chinnery et al. proposed that 14.2% of individuals have an ultra-rare DNA segment found in under 1/1000 people.

Mitochondria. Image: Flickr

So, what role do these mitochondrial DNA fragments play in the nucleus? One theory suggests that mtDNA helps to stick back together DNA which has been severed. This theory is supported by the fact that many mtDNA fragments were found next to binding sites for a protein involved in DNA repair called PRDM9.

Occasionally, insertion of mitochondrial DNA may go wrong and have implications in cancer. Though the majority of mtDNA insertions occur in the non-coding regions of DNA (known as introns), in rare cases they may be inserted into coding regions of the genome which could drive tumour formation. Interestingly, Chinnery et al. found that mtDNA was more likely to be found in tumour DNA, appearing in 1/1,000 cancers from 12,500 samples. This invites further investigation of mtDNA in cancer which may prove useful for future therapeutic application.

This discovery leaves us with a slightly different perspective of mitochondrial DNA which is not as dormant as was once believed. This research shows that even after billions of years, the once independent, energy-producing bacterium may not have completed their role in endosymbiosis after all. Further work is now required to explain exactly how mtDNA navigates into the human genome and what impact this has human evolution.

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