The new discoveries by the team of microbiologists, physicists and geneticists, led by Dr Justin O’Sullivan of the University of Auckland, turn around how cells switch their genes on and off to function. The team has uncovered new explanations for how this may be occurring.
By studying the shape and structure of the DNA inside the cell, the team discovered for the first time a microscopic, effortlessly efficient organisational structure that is linked to when genes turn on and off. This “on/off” switching of genes makes cells different from one another.
There are about 200 different cell types in the body, all with the same DNA information, but each with completely different functions. For example a skin cell and a hair cell are genetically identical, but different, specific genes in them are turned on and off. “How is it that cells are different, even though they have the same DNA?” asks Dr O’Sullivan. “With this paper, and an earlier one, we think we have discovered part of the mechanism.”
The team now believes that the DNA in a cell is not arranged randomly and chaotically (as has long been believed), with the long double helix DNA stuffed into the nucleus. The Gravida team believes the DNA is ordered in the nucleus.
“The DNA is folded in the nucleus. It is folded so that certain bits of DNA, certain genes or chromosomes are juxtaposed together,” says Dr O’Sullivan. “This means certain genes come directly into contact. They are mapped together deliberately in the nucleus. This creates an efficient process. It means that genes and chromosomes that need to work together to make cells different from one another, don’t have to ‘wander around the nucleus’ trying to meet up.
Chromosomes and genes meet because they’re folded together quite precisely.”
“For the first time, we’ve shown you can’t separate the structure of a cell from its function. If a cell has a different structure, if the DNA is folded a certain way in one cell and not in another cell, the cell itself has a different function. The juxtaposition of chromosomes and genes is linked to genes turning on and off.”
"Furthermore, the structure is self-organising. The cell is not doing this in a way that requires membranes. It’s just a spatial organisation setting up domains of chromosomes to perform functions.”
The team related this new finding to another completely ‘novel’ research discovery they made, and published in the international journal Mitochondria, in June this year. In the research published in June, Gravida’s team found that the mitochondria also directly connects with genes that are turned on. Previously, most scientists believed that the mitochondria was simply the cell’s powerhouse, and had nothing to do with nuclear genes. Science for a long time considered that the mitochondria had the remnants of a genome.
Previously, mitochondrial DNA in the nucleus was thought to do nothing and considered ‘junk DNA’. The team found that the mitochondria send a little bit of their “genome” back to the nucleus and they do this with a purpose so it isn’t junk at all.
“This physically connects with the DNA from the cell already in the nucleus. Thus the mitochondria are shifting genetic information around inside the cell,” says Dr O’Sullivan. “When the bits of mitochondrial DNA go across to the nucleus, they change the way the cell reads the information in the nuclear library. They change the way the cell interprets its nuclear DNA and its genes. That’s pretty amazing.”
“What we think is happening is that the mitochondrial DNA is pivotal in contributing to the way the cells are developing, as they change to skin cells, or a cell that makes melanin, or one that makes a red blood cell. The mitochondrial DNA contributes to the development pathway through the spatial organisation of DNA and genes in the cell nucleus. So it’s not junk DNA at all: it’s just not coded. We’re finding out that its function is determining the spatial organisation of the genome – the way the DNA is folded, which in turn determines what chromosomes are touching one another, and which are turned on and off,” says Dr O’Sullivan.
Dr O’Sullivan says that this is an essential insight into the nature of disease. “If you have the wrong combinations of chromosomes associated together in space, you could be turning the wrong functions on and off in the genes,” he says.
“This is a leading edge discovery,” says Professor Phil Baker, director of Gravida.
“There are only a couple of other labs around the world doing this sort of work, and Gravida’s team is the first to discover this. Again, Gravida is at the forefront of cutting edge research.” Gravida brings together leading biomedical and clinical scientists from around and the world to identify conditions encountered in early life that affect the way people grow and develop throughout life.”