Essential Genes Cluster Clue To Order In The Genome

"There may be a real code to chromosomal organization," said Dr. Monica Justice, associate professor of molecular and human genetics at BCM and an expert in mouse genomics. Chromosomes are cellular structures that contain genes. Humans have 23 pairs. One of each pair comes from the mother; the other from the father.

This is the first time anyone has been able to look at the issue of essential genes in the mouse, said Justice. Essential genes are those that are crucial to the life of an organism. When these genes are lacking, the animal does not develop normally and dies.

"The area of mouse chromosome 11 on which we focused is homologous to or has the same genes as human chromosome 17," said Justice. "It is very gene-rich, but it also seems to have a lot of genes that when mutated, cause the animal to die."

She said she and her colleagues chose this chromosome because all the genes present on the homologous region on human 17 could actually be found on mouse chromosome 11.

"When we saw that there were all these essential genes in this region, we wondered if the reason that the chromosome remained together (and is not easily broken apart or recombined with other parts of this or other chromosomes) is that it had all these densely packed essential genes," said Justice.

With the aid of a computer program developed by Dr. Bin Liu at Baylor College of Medicine, the researchers analyzed this region across species as diverse as possum, cow, dog and chimp. "We found it was highly conserved across species," she said.

"The reason this part of the chromosome has remained intact is that it has densely packed essential genes. If the chromosome broke anywhere, the organism would not develop," she said.

The finding also begs the question as to whether genes need to be transcribed (or have their message read to enable production of proteins) at the same or similar times during development, to be organized in a certain way in the nucleus and remain together, she said. She anticipates that many laboratories, including hers, will begin to pursue that question.

Drs. David Pollock of the University of Colorado Health Sciences Center in Aurora and Kathryn E. Hentges of the University of Manchester in the United Kingdom also took part in this research.

Funding for this work came from the U.S. Public Health Service.

PLoS Genetics is an open-access journal. The full article can be read at http://dx.doi.org/10.1371/journal.pgen.0030072 after publication.