Researchers at the Weizmann Institute discovered that the chromosomes spend only a short period of time in the form in which they are usually drawn - an X shape.
It is customary to present the chromosomes - those 46 well-packaged packages of genetic material found in all the cells of our body - as resembling the letter X, but in fact those ordered "X's" appear only at the stage when the cell is about to divide, after all its genetic material has undergone duplication. Until now, scientists did not have a clear picture of how our DNA molecule - a double helix about two meters long - is organized in an orderly manner inside the nucleus, in a structure that allows for the ongoing activity of the genes within it. A combination of two new methods for DNA sequencing in individual chromosomes, and analysis of data obtained from thousands of measurements, now reveal an unfamiliar picture of the three-dimensional structure of chromosomes. The new method, the result of joint work by scientists from the Weizmann Institute of Science and scientists from England, Shwas published recently in the journal Nature, will help scientists understand the basic processes that control the expression of genes and maintain the stability of the genome.
Prof. Amos Tani from the Department of Computer Science and Applied Mathematics and the Department of Biological Control at the Weizmann Institute of Science developed an algorithm for analyzing genomic data sets, capable of scanning billions of bits of information. Together with the members of his team, which included research students Yaniv Lubling and Eitan Yaffe, and in collaboration with Dr. Peter Fraser from the Barham Institute in England, Prof. Tanai succeeded in deciphering the architectural structure of the chromosome with an unprecedented resolution. Instead of using traditional microscopic methods, as is customary, the scientists took advantage of modern and powerful DNA sequencing methods.
The basis for the new method was laid by Dr. Fraser and his team members, who developed sophisticated methods for DNA sequencing that use thousands of measurements of the points of contact between genes found on a single chromosome. These methods are a significant improvement over the approaches that preceded them, which were based on a structural average of millions of chromosomes. However, although it analyzes a tiny amount of DNA (several trillions of grams), originating from a single cell, Dr. Fraser's method generates enormous amounts of information, and uses advanced statistical methods for its analysis. Prof. Tanai and his team members performed the complex computerized analysis, through which millions of DNA sequences were turned into reliable maps describing the connections between genes along the chromosome. Using these maps, the team, in collaboration with Dr. Ernest Law of the University of Cambridge, was able to produce three-dimensional models describing the structure of individual chromosomes.
Deciphering the architectural structure of the chromosomes at a high resolution level points to an interesting fact: the structure of one DNA molecule may vary from cell to cell. At the same time, the results provide several general principles that determine the way the genes are organized in the chromosome: the organization is modular, and is based on the function of the genes found in the chromosome. For example, the data indicates that the chromosome reveals the genes that must be activated by pushing them to the ends, thus allowing those genes to come into contact with the cellular machinery that controls their expression.
The new method not only provides a unique and surprising look at the structure of the chromosomes in cells, but provides geneticists with a powerful research tool. For example, it may help reveal the variation in genetic activity between different types of cells, as well as contribute to understanding the mechanisms that determine why certain genes are active and others are inactive in health or disease states. The rapid improvement in technologies for sequencing huge amounts of genetic material ensures that this type of research will gain momentum in the near future.
For more details, you can contact the Weizmann Institute of Science spokesperson's office: 08-9343856
