Cues for DNA curl-up inside us just as important as genetic code – study

© National Human Genome Research Institute
Taking a well-known concept, theoretical physicists (of all people) observed for the first time that our DNA hides embedded instructions for the strands to fold a certain way – instructions that can also affect mutations.

Most of us have known for a while what we learned in biology class – that a particular arrangement of the gene code comprising the letters A,C,T, and G, is what gives us our traits; from eye color to disease propensity, it’s all in there. And, of course, you can also add environmental factors, which have been proven to turn some genes on and off, leading to particular physical traits or behaviors suddenly gaining prominence.

But all of the above is only 50 percent correct. Because since the 80s we’ve also known of a second layer of information that governs how we look and feel – our DNA’s mechanical properties.
In fact, all cells in our body already contain all of our information. But what distinguishes, say, a hair cell from a skin cell?

The answer is in the prominence each gene combination is given inside each cell. There are two meters of DNA inside each cell. The only way to fit it all in there is to fold it. These clusters of folded DNA on a reel are called nucleosomes. The type of fold determines what a cell does, and how, and which proteins it actives and hides.

We’ve also guessed for some time that there must be a way for science to grab hold of some strands and change the way they are folded, giving different genes prominence. A different technique could be changing the shape of the rod on which the nucleosomes rest.

All of this until now was in the academic domain of biology, as to be expected. But now a group of theoretical physicists have been able to demonstrate for the first time through simulations how this hidden information controls our traits. And they claim to have proved that the instructions for how the DNA strand is folded are embedded also within us.

"The mechanics of the DNA structure can change, resulting in different packaging and levels of DNA accessibility and therefore differing frequency of production of that protein,” explains the team at Leiden University in the Netherlands, who undertook the research.

Led by physicist Helmut Schiessel, they showed that the cues embedded in us controlled how the DNA was folded, and which properties it expressed. They did this by taking baking yeast and fission yeast and then embedding mechanical cues into their respective DNA sequences. The resulting computer simulation proved the theory.

Concluding that this second layer of information does exist, the team knows genetic mutations and various defects are also a result of that. Being able to manipulate the folds and assign our own cues to DNA behavior, we may be able to engineer disease-free humans, although the Leiden team admits we’re still too far away from that.