The understanding between scientists as to how DNA is packaged has shifted from being less like a shoe lace and more like a yoyo string… stay with us, there is a little more to it than this.
Scientists knew that DNA could be uncoiled from the structural unit of a chromosome, known as a nucleosome, but it was assumed that the two ends were symmetric. This would have meant that the uncoiling of the DNA would be much like the untying of a shoe. University of Illinois researchers found that the DNA is actually very asymmetric, like the string wrapped around a yoyo. This would essentially mean that pulling on one end of the DNA would tighten the coil, while pulling on the other would cause it to uncoil like a yoyo.
This is an appropriate analogy, but to cram so much genetic information into a tight space is not as simple as this might make it sound. To pack two meters of DNA into a microscopic cell, the string of genetic information must be wound extremely carefully into chromosomes.
“Still Suprises in the Physics of DNA”
Professor Taekjip Ha, a member of the Carl R. Woese Institute for Genomic Biology at the University of Illinois said: “We discovered this interesting physics of DNA that its sequence determines the flexibility and thus the stability of the DNA package inside the cell. This is actually very elementary DNA physics. Many people thought we should have known this many decades ago, but there are still surprises in the physics of DNA.”
The physics of the packaging is determined by the DNA’s sequence, which makes the strand of DNA flexible enough to strike a balance between two opposing principles: it has to be stable enough to compact DNA, but dynamic enough so the strand can be uncoiled and read to make proteins.
Professor Ha said: “There are many good studies that show that if you change the sequence of the gene, then it will affect other things. Different proteins may be created because they require certain sequences for binding and so on. But no one had really thought about sequence changes having an effect on DNA physics, which in turn causes changes in the biology.”
“Major Impact on How DNA is Read”
His research has shown that it is easier for the cell’s protein-making properties to read from the ‘weak’ end of the nucleosome that uncoils more easily. It also suggests that genetic mutations related to diseases alter the stability of the nucleosome. Ha explains: “This could have a major impact on how the information is read out and how different proteins are produced. For example, cancer-fighting proteins or cancer-causing proteins may be made differently depending on the changes in the DNA flexibility and stability caused by mutations.”
Professor Ha is hardly going to stop at this achievement of his recent discoveries. His ambitious future plans include using next generation sequencing to determine the flexibility of an entire genome. He hopes to create the first genome-wide map of physical properties. He also wants to find out if mutations can make the DNA easier or more difficult to read.