An international team of researchers, in collaboration with the University of Durham, UK, has recently made an important discovery in the field of genetic engineering. They managed to develop an innovative experimental protocol that allowed them to decipher the mechanical code of DNA. Recall that the mechanical code of DNA refers to the physical properties that are critical to its function as a genetic material. Among the best-known mechanical codes are the structure of the double helix, the stability of base pairing, or the elasticity of the DNA molecule.
With this new DNA sequencing method, called loop-seq, the team was able to lift the veil on the exact nature of the biological information contained in a DNA sequence. The researchers hope that this knowledge will guide future therapeutic and bioengineering developments.
They described their new technology in the journal Nature Structural & Molecular Biology.
The researchers deciphered the mechanical code of DNA using loop-seq.
Loop-seq has helped researchers learn more about the structure of DNA. In particular, this allowed them to demonstrate that a certain sequence of bases along a stretch of DNA determines the local flexibility of the molecule. By combining the information collected during sequencing with computer analysis and machine learning, they were able to determine the mechanical code. It is this mechanical code that gives the correspondence between the local sequence and the local deformability of DNA.
In addition, the researchers found that the mechanical code of DNA can be changed by “methylation”. Methylation is a chemical modification in which DNA bases regularly undergo various developmental stages in an organism. It intervenes to regulate gene expression through the addition of methyl groups to cytosines. This chemical modification allows DNA to change the genetic code without changing its sequence.
Aberrant methylation contributes to diseases such as cancer.
In this study, the scientists also found that DNA methylation can go awry. Hypermethylation or aberrant methylation is one such genetic epiphenomenon. However, this excess methylation changes the mechanical code. Diseases such as cancer partially affect cells by changing the information encoded in the mechanical code. Therefore, aberrant methylation has been associated with the occurrence of several types of cancer and can be considered as a diagnostic marker of these diseases.
To better explain this phenomenon, Dr. Aakash Basu of Durham University, the lead author of this study, compared DNA to a book containing the instructions cells need to survive. Only with this special kind of book, your ability to turn the page, patch a hole, or fold this one depends on the words that are written there. And that those words in the book also somehow control the mechanical properties of the paper.