Last updated January 23, 2018 at 11:04 am
New methods allow scientists to explore untapped territory. In this latest discovery, researchers have developed a method to isolate and distinguish different DNA from different tissues.
Credit: iStock
Researchers have found that the rate of genetic mutation in mitochondrial DNA vary across different tissue types, with the highest rate occurring in reproductive cells.
Until now, researchers have not been able to isolate mitochondrial DNA from whole organisms in a way that is cell-specific. That is, they have not been able to determine which cells – and thus which tissue – that specific mitochondrial DNA came from.
They achieved this using Caenorhabditis elegans (C. elegans), a tiny, see-through nematode that is a common model for genetic research as it shares about 60-80% of its genes with humans, and its transparency makes it useful for tracking cell activity.
DNA exists in our cells as nuclear DNA (named so because it exists within the nucleus of the cell) but our cell also contains DNA in the mitochondria, an organelle that is vitally important to our bodies.
“Mitochondria are known as the cell’s power plant – they are found in all animal and human cells – and in humans they generate about 90% of the body’s energy from the food we eat and the oxygen we breathe,” explained Dr Steven Zuryn, leader of the Queensland Brain Institute team behind his study.
Mitochondria DNA remains a target of interest to scientists as a number of age-related diseases such as neurodegenerative diseases, as well as diabetes and cancer, are associated with mutations that affect mitochondria functionality.
Cell-specific mitochondrial affinity purification system. Credit: Zuryn et al./Natural Cell Biology
New methods, new possibilities
By creating a sophisticated fusion protein that is switched on and controlled by a specific tissue, it allows for the researchers to isolate tissue-specific mitochondria in the C. elegans.
A protein subunit (TOMM-20) is tagged with HA and mKate2 (a red fluorophore) and expressed under a tissue-specific promoter, such as the body wall muscle. Homogenisation of the animals releases total mitochondria from all the different tissues. Tissue-specific labeled mitochondria (red) can then be purified and isolated.
This approach allows for direct comparison of mitochondria from different tissues and to determine the level of mitochondrial DNA mutations in individual cell types.
They have now established that there are mutations in mitochondrial DNA that are specific to tissues and that their frequency of gene mutations differs in different cells and tissues. There are higher rates of mutations in germline (reproductive) cells than regular somatic (any cell other than reproductive) cells.
“Mitochondrial DNA is only passed down from the mother’s side, and transmits the genetic information from one generation to the next,” said Dr Zuryn.
But if these mutation rates are as high as they are, it would be assumed there would be higher rates of mitochondrial-related diseases.
“We now suspect that there is a mechanism in all animals that can filter out these mutations before they are passed to future offspring, which could otherwise cause a multitude of diseases affecting the brain,” Dr Zuryn said.
With this method they developed, it can be applied both at the individual level and large populations, which will help future studies looking at large-scale trends to achieve this efficiently.
This paper was published in Nature Cell Biology.
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