Tiny DNA building block is identical regardless of species

Wednesday 21 Oct 15


Jakob Bohr
DTU Compute
Professor Jakob Bohr is working on a theory to explain why a specific building block in chromosomes is identical in people, animals and plants.

The diameter of a single, cylindrical DNA component is always the same, regardless of whether it forms part of a fruit fly, a beech tree, or a human being. This tiny building block in the DNA architecture is part of what is known as the nucleosome. The diameter of the nucleosome has long been a source of fascination for Professor Jakob Bohr of DTU Nanotech. Because if it is the same in all species, what universal principle or law of nature is in effect?

“As a physicist, I attempt to find the answers to these questions in the worlds of mathematics and physics. And in these contexts, our calculations demonstrate that the size of the nucleosomes makes perfect sense. They create what we have chosen to call ‘twist neutrality’,” relates Jakob Bohr, who has been studying the diameter of the nucleosomes in partnership with his colleague, Kasper Olsen.

“Twist neutrality ensures that the number of turns in the DNA material always remains constant, such that the smallest structure in DNA architecture—the DNA helix—can be stretched without affecting the number of twists. This property is essential in nature every time DNA material needs to be copied; in the case of cell division, for example. Briefly put, twist neutrality helps prevent the twists becoming entangled and damaging our DNA,” he adds.

"Twist neutrality helps prevent the twists becoming entangled and damaging our DNA."
Professor Jakob Bohr, DTU Nanotech.

The nucleosome is only a tiny part of the complex DNA architecture. In total, every single sell contains more than a metre of DNA, and to make room for so much material, the DNA is twisted and folded together over and over again. This leads to the creation of what can be perceived as different levels of structuring, and depending on how a level can actually be defined, eight such levels are created.

“Each level alters the scale of our hereditary material by a factor of around three, in the same way as when you fold a piece of paper repeatedly, the thickness is increased by a factor of two every time. This compression of the DNA ensures that it is small enough to fit inside the nucleus of the cell,” explains Jakob Bohr.

The highest level of DNA comprises the chromosome structures, where the gender chromosomes—X and Y—are the best known. The bottom level, i.e. the tiniest structure in the DNA architecture, is the famous double helix, the eye-catching spiral of two strands of DNA winding around one another.

Chromosome architecture  


The illustration shows a very simplified, comic strip view of the organization of DNA. The organization serves to compress the over one-metre long DNA, so it can fit inside the cell nucleus. If you ‘read’ the figure backwards—i.e. from H to A—it corresponds to looking at a chromosome, then ‘zooming in’' step-by-step, so you finally end with the chromosome’s smallest structure—the DNA helix in Figure A.

Figure A The well-known double helix—the spiral with the two strands of DNA is the smallest structure in the chromosome. Here it is reproduced without the base pairs that connect the two strands and which cause the spiral to resemble a spiral ladder.

Figur B shows how the double helix is wound twice around a cylindrical core of proteins. This structure is called a nucleosome. It is the diameter of this structure which is the same across different species—and which fascinates Professor Jakob Bohr. The proportions in this figure do not correspond to the real world, where the DNA helix is equal in size to the protein core.

Figure C shows the row of nucleosomes, causing the structure to resemble a chain of pearls.

Figure D-G illustrates the next levels, where the material DNA is further packaged. As yet, the geometry of these levels is not fully clarified.

Level H illustrates the contours of the chromosome as viewed under a microscope.

The natural law of the twists
At the level before this, the double helix is wound twice around a collection of proteins. This is the structure that is called a nucleosome. It takes a lot of nucleosomes to wind up the entire double helix, and this makes the structure resemble a string of pearls—where the nucleosomes are the pearls and the double helix is the chain.

The calculations performed by Jakob Bohr and his colleagues demonstrate that if the diameter of the nucleosomes were different, twist neutrality would simply not exist.

“This would not be good, because it would mean that new, inappropriate structures could appear in the DNA. So we think that the reason why the size of the nucleosomes remains constant across species is that there is no benefit to nature in developing or changing this size. Otherwise, we would probably have encountered it as a stage in the evolutionary process,” explains Jakob Bohr.

New technology should help
The long-term aim of the research into the diameter of the nucleosomes is to contribute to a complete description of the geometry of DNA. This could help reveal general principles for the construction of the chromosomes, which would enable us to understand them in even greater detail.

“Because even though we can already mine down to gene level in the double helix—the lowest level in the chromosome—a number of the other eight levels are still largely uncharted territory. Simply put, we have no idea what structures exist on some of the other levels,” adds Jakob Bohr.

According to Jakob Bohr, researchers do not currently have access to technology with the capacity to clarify the structures completely at all levels of the chromosomes. However, he is sure that the technology required should appear over the coming 10–15 years, possibly as a result of other research into bioinformatics and via the new facilities including ESS and MAX IV in Lund. 

Article in DTUavisen no. 7, October 2015.