Understanding the structure of the human genome is critical to understanding its function as a whole, according to USC professor Lin Chen. Image: University of Southern California |
For the first time, scientists have developed a method for generating
accurate 3D models of the entire DNA strand of a cell, known as a genome
The genome plays a central role in the functions of almost all human cells, and
flaws in its structure are thought to cause various disorders, including
cancer.
Understanding the structure of the genome is crucial to understanding its
function as a whole, said Lin Chen, professor of molecular biology at the University
of Southern California (USC) Dornsife College of Letters, Arts and Sciences.
“Everything biological works in the three dimensions,” Chen said. “Therefore, to understand it completely, you have to understand it
three-dimensionally.”
The genome inside a cell can be thought of as a bowl of angel hair pasta.
Different cells are like different bowls of pasta in which the noodles are
organized differently overall, but they share certain features.
The technique adds a crucial piece of the puzzle for scientists trying to
understand the genome in normal and diseased cells. One of the most likely
applications of this research will be to identify potentially cancerous cells
based on structural defects in the cell’s genome, Chen said.
“Hopefully in the future, these studies allow scientists to better
understand how the genome is involved in disease and how its function can be
regulated in those circumstances,” Chen said.
Because of its tiny size and monstrously long length, creating a 3D image of
a genome is not as simple as taking a photograph. The genomic DNA strand is so
long that if a nucleus was the size of a soccer ball, the strand of DNA inside
it could be unraveled to stretch more than 30 miles long. Nothing biologists
normally use for studying the structure of biomolecules works well for the
human genome.
Scrunched up inside the nucleus, the DNA forms hundreds of millions of
contacts with itself. Using a new technique, USC researchers plotted out the
location of each of those DNA-on-DNA contacts and used sophisticated computer
algorithms to model the results in 3D.
“It provides you with a completely new prospective in the genome,” Chen
said. The study appears on the Nature Biotechnology Website.
By analyzing the differences and similarities in genome structure between
various cells, scientists are able to discern what basic principles of 3D
organization are. In addition, the structure allows scientists to see where
each gene is located relative to any other gene and how this arrangement is
important to cellular functions.
The method used by the USC team takes into account the fact that each cell
is slightly different—the DNA does not always scrunch in the exact same way.
“There is not a single structure of a genome,” said Frank Alber, assistant
professor of computational biology at USC Dornsife. Chen and Alber led a team
of USC researchers, including Reza Kalhor, Harianto Tjong, and Nimanthi
Jayathilaka, that solved the problem.
By doing a statistical analysis of many genomes, the team was able to
determine “preferred positions” for the DNA strand, providing an idea of how it
most likely is to appear.
