From genome comparisons, researchers learn lessons about evolution and cancer.

2003 NOV 6 - (NewsRx.com & NewsRx.net) -- In 1905, American astronomer Percival Lowell predicted the existence of a new planet he called Planet X. Lowell proved that this new planet existed even though no one had been able to see it in the sky. Twenty-five years later, astronomer Clyde Tombaugh stumbled on images of X photographed from the Flagstaff Observatory in Arizona. Today, that planet is known as Pluto.

While it took 25 years for astronomers to go from theory to confirmation of Pluto's existence, it took genome scientists barely 3 months in 2003 to confirm a revolutionary new view of what happens in the human genome to cause dramatic evolutionary changes. Now, bioinformaticians at the University of California, San Diego (UCSD) - who posited that 'fragile' regions exist in the human genome that are more susceptible to gene rearrangements - are collaborating with biologists to see if their new theory can yield potentially life-saving insights into diseases such as breast cancer, in which chromosomal rearrangements are implicated.

"It took only 3 months to go from theory to hard scientific evidence that there are regions of the genome that are subject to evolutionary 'earthquakes' over and over again," said Pavel Pevzner, who holds the Ronald R. Taylor Chair in computer science and engineering at UCSD's Jacobs School of Engineering. "That is representative of how quickly knowledge is advancing in bioinformatics, and how useful this research can be for medicine and other fields."

In June, Pevzner and UCSD mathematics professor Glenn Tesler predicted the existence of evolutionary 'fault zones' - hotspots where gene rearrangements are more likely to occur and change the architecture of our genomes. Their work was based on computational analysis and comparison of the human and mouse genomes. In a paper in the journal Proceedings of the National Academy of Sciences USA (PNAS), Pevzner and Tesler estimated that these fault zones may be limited to approximately 400 fragile regions that account for only 5% of the human genome. While reaching that estimate using computers, the researchers were not yet able to point to specific locations in the genome where these rearrangements are more commonplace (Pevzner P, Tesler G, Human and mouse genomic sequences reveal extensive breakpoint reuse in mammalian evolution. Proc Natl Acad Sci USA, 2003;100(13):7672-7).

The PNAS paper departed from the prevailing "random breakage" theory of evolution that has been widely held for nearly 2 decades, but the theory of "fragile breakage" quickly gained acceptance. A team led by UC Santa Cruz scientists Jim Kent and David Haussler, who are widely credited for their work in the public-sector assembly of the human genome, were the first to confirm the UCSD results. In addition, for the first time, they explicitly pinpointed the location of some of the faults in the human genome.

Kent's findings were published in PNAS, along with a commentary by two pioneers in ...