Why did some people experience more severe coronavirus symptoms than others during the Covid-19 pandemic? International researchers believe part of the answer may lie deep within human cells, specifically in the small circular chromosome inside each cell, called the mitochondrial DNA.

Genetic variations in mitochondrial DNA are considered the key to unlocking answers about the innermost workings of cells and mapping the way forward for more effective medical treatment.

Dr Marianne Pretorius*, senior lecturer in Biochemistry at the North-West University (NWU), is part of a major international research project that probes genetic variations in mitochondrial DNA.

The first part of the study, involving research in the USA, India and South Africa, will explore the effects of differences in the mitochondrial DNA of different populations on the severity of viral diseases such as Covid-19.

Creating cells for impactful research

Dr Pretorius’s main contribution to the project will be to provide cybrid cells representing African populations through which the effects of differences in mitochondrial DNA can be explored. Cybrids are hybrid cells that all contain the same nuclear genes, but the mitochondrial DNA is from donor cells.

Since mitochondrial DNA is passed on only from mother to child, different population groups have distinct mitochondrial DNA patterns and can be assigned to mitochondrial haplogroups, the origins of which can be traced back tens of thousands of years.

It is possible that haplogroup background plays a role in how severely mitochondrial functions are affected in a disease state.  

Dr Pretorius grows the cybrid cells in the laboratory. She uses a basic laboratory cell line ― in this case the 143B cell line. This cell line is then treated with chemicals that break down mitochondrial DNA to create a background cell line without any mitochondrial DNA, which is called an rho0 cell.

Blood platelets contain mitochondrial material but almost no other cellular components, and can be used to introduce a donor’s mitochondrial DNA into the rho0 cells. Dr Pretorius will isolate platelets from blood donated by study participants who have mitochondrial haplogroups representing African population groups.

She will then fuse these platelets from different donors with the treated laboratory cell line. This creates a series of cells with the same nuclear DNA background, but with different mitochondrial DNA. Through this, the effect of differences in mitochondrial DNA can be studied on its own without including other differences between donors.

Bringing African populations into the mix

The study is an international collaboration between researchers from the NWU, the Children’s Hospital of Philadelphia in the USA and Hyderabad University in India, with the specific goal of adding cybrids representing African and Indian populations to the existing European collection.

Dr Pretorius’s research focus is specifically on African populations. “The purpose is to include African populations in the study, since African populations have unfortunately been understudied in major research projects so far, despite their unique genetic diversity. Most published genetic research was done in European populations or those of European descent.”

She says research findings on European populations are not always compatible with those on African groups. “My aim is to determine if there is a difference in the cells that represent various population groups and in what way they react differently when they are infected. If there is a difference, I want to find out what drives those differences.”

Once completed, the biggest impact of her research will be to chart the way forward regarding how various population groups should be approached when they need treatment for viral infections and other diseases.

“This is important in making a difference to the health and well-being of patients worldwide, but is especially needed in Africa, where there still is a lot to be researched in this regard,” she concludes.

For more information about research on mitochondrial DNA, email Dr Pretorius at Marianne.pretorius@nwu.ac.za. She is currently recruiting participants for this study. If you would like to take part and find out more about your own maternal genetic heritage along the way, see here for more information.

*Dr Pretorius publishes her research under the name Marianne Venter.

Dr Marianne Pretorius