Function Follows Form? Researchers Deciphered Complete 3-D Structure of Bacterium's Chromosome

Knowing the three-dimensional shape of a cell’s chromosome can help in understanding genetic sequences and how genes are regulated; however, until now, it has been nearly impossible to analyze the shape and structure of a chromosome’s genome in its entirety.

Luckily, a group of researchers at University of Massachusetts Medical School, Harvard Medical School, Stanford University, and the Prince Felipe Research Centre in Spain recently deciphered the three-dimensional structure of the chromosome of the bacterium Caulobacter crescentus using both molecular and 3-D modeling technology, specifically high-throughput chromatin interaction detection (known as “5C” technology), advanced DNA sequencing techniques, computational modeling, and fluorescent microscopy.

[caption id="attachment_3351" align="alignright" width="185" caption="C. crescentus, shown above, is a single-celled, Gram-negative, rod-shaped bacterium. (Image source: Yves Brun, courtesy of Indiana University)"][/caption]

In order to “create” the image, they used the 5C technology to map more than 28,700 contact points in the bacterium’s genome and used these points to then approximate spatial distance in the folded chromosome. In doing this, they discovered unique characteristics of a specific genetic sequence called the parS site, which helps to define the chromosome's shape (which was found to be ellipsoidal with helically-arranged arms on both sides). They determined the importance of the parS site by creating mutant bacteria in which the site was in a different location, and observing that the entire genome had rotated clockwise, changing the shape of the entire chromosome.

This new experimental method is crucial because the previous technique used in analyzing genome structure – trying to form conclusions by studying the positions of genome loci – was not thorough enough to study any whole genome at once. As Dekker, one of the authors of the study, noted, “This study illustrates how an investigation of 3D genomic structure can provide insights into how the complex relationships between genome sequence and structure can impact function.” I think that these researchers’ approach was novel because they studied the chromosome in a three-dimensional, or realistic, way – biological structures, especially chromosomes, have complex shapes that are difficult to visualize.

The abstract of the original research article can be found here.