Fission yeast genome……Credit: Wistar Institute

It looks like a loose ball of yarn, as in the picture above. In fact, it’s the genome of a common yeast (S. pombe). The human genome spends most of its time in a ball something like this. The familiar “X” shaped chromosomes occur only at the time of cell division. Like almost everything biologists are discovering about the cell, the shape of the genome isn’t arbitrary. A new study, conducted by Ken-ichi Noma and colleagues at the Wistar Institute (Philadelphia, USA) and published in the October 29, 2010 issue of Nucleic Acids Research [ Mapping of long-range associations throughout the fission yeast genome reveals global genome organization linked to transcriptional regulation ] shows that the shape of the yeast genome has real significance.

‘Shape’ in this case means the three-dimensional structure. By (stretched) analogy it’s like the mess on and in your desk. The important stuff is on top. That includes things you need every day and the current things you’re working on. Less important stuff is buried on top, or jammed into drawers where you (mostly) remember where to find them. The genome ball of chromosomes is something like this. Important genes are placed so that they can be more easily reached by transcription factors (RNA material).

To reach this conclusion Noma and his colleagues combined latest-generation DNA sequencing (equipment) with a technique known as chromosome conformation capture (3C – developed in 2002 by Dekker and colleagues at the University of Massachusetts). The 3C technique is tricky, but it does help clarify the conformation (shape); the researchers used this in conjunction with fluorescent probes to locate specific genes through a microscope. From this they were able to ‘map’ three-dimensional computer models of the yeast genome.

The advantage of their new technique is the ability to view genes as they interact with each other. They were able to identify 465 groups of genes that share a similar function (gene ontology groups). The physical relationship of genes in these groups was often significant:

“When the chromosomes come together, they fold into positions that bring genes from different chromosomes near each other,” Noma said. “This positioning allows the processes that dictate how and when genes are read to operate efficiently on multiple genes at once.”

This structure is not merely an accident of chemical attractions within and among the chromosomes – although that is certainly a part of the larger whole – but an arrangement guided by other molecules in the cell to create a mega-structure that dictates genetic function, Noma says. He envisions a scenario where accessory molecules, such as gene-promoting transcription factors, bind to DNA and contribute to the ultimate structure of the genome as the chromosomes fold together.

[Source: Wistar Institute]

Keep in mind that this research was done on the genome of yeast, a relatively simple beasty with only three chromosomes. The human genome presents a more complex challenge. Nevertheless, Noma and other researchers are turning to new techniques that give them a picture of how elements of the genome interact. The physical relationships can tell them a lot about the timing, priority, and chemical activity of various DNA processes – RNA transcription in particular. The real insights will come from future work.

In addition, work in other areas of genome sequencing will undoubtedly influence the research into the importance of genome shape. For example, a study released on the same day as the Wistar paper revealed new information about the amount and versatility of copied genetic sequences [SciTechStory: DNA redundancy: Genetic sequence copies are more prevalent and important than thought] Almost all genes have a copy in the genome, but some are more copied than others. How these copies interact will also have a physical dimension.