[meteorite-list] Multi-Species Genome Comparison Sheds New Light on Evolutionary Processes, Cancer Mutations

From: Ron Baalke <baalke_at_meteoritecentral.com>
Date: Fri Jul 22 15:18:54 2005
Message-ID: <200507221918.j6MJI2q13647_at_zagami.jpl.nasa.gov>

http://www.nih.gov/news/pr/jul2005/nhgri-21.htm
 
National Human Genome Research Institute (NHGRI)

EMBARGOED FOR RELEASE
Thursday, July 21, 2005
2:00 p.m. ET

CONTACT: Leslie Saint-Julien
301-402-0911

Multi-Species Genome Comparison Sheds New Light on Evolutionary
Processes, Cancer Mutations

Bethesda, Maryland - An international team that includes researchers
from the National Human Genome Research Institute (NHGRI), part of the
National Institutes of Health (NIH), has discovered that mammalian
chromosomes have evolved by breaking at specific sites rather than
randomly as long thought - and that many of the breakage hotspots are
also involved in human cancer.

In a study published in the July 22 issue of the journal Science, a team
of 25 scientists from the United States, France and Singapore compared
the organization of the chromosomes of eight mammalian species: human,
mouse, rat, cow, pig, dog, cat and horse. Using sophisticated computer
software to align and compare the mammals' genetic material, or genomes,
the team determined that chromosomes tend to break in the same places as
species evolve, resulting in rearrangements of their DNA. Prior to the
discovery of these breakage hotspots, the prevailing view among
scientists was that such rearrangements occurred at random locations.

"This study shows the tremendous power of using multi-species genome
comparisons to understand evolutionary processes, including those with
potential relevance to human disease," said NHGRI Scientific Director
Eric D. Green, M.D., Ph.D. "The dog genome map generated by NHGRI
researchers and their collaborators played a key role in these new
analyses. Furthermore, the team took full advantage of the wealth of
human, mouse and rat genome sequence data generated by the recently
completed Human Genome Project."

Chromosomes are the threadlike "packages" of DNA located in the nucleus
of each cell. When cells divide, a chromosome occasionally breaks and
the fragment can get stuck onto another chromosome. In addition,
fragments may break off from two different chromosomes and swap places.

Chromosomal breakages, also referred to as translocations, are thought
to be important in terms of evolution. When chromosomes break in egg or
sperm cells, opportunities arise for the rearrangement of DNA in the
resulting offspring. Such inheritable rearrangements may be lethal or
cause disease. However, in some cases, the breaks may lead to the
production of new or altered proteins with potential to benefit an
organism. In addition to their evolutionary implications, chromosomal
translocations are known to contribute to the development or progression
of many types of cancer.

In their paper, researchers report that the chromosomal abnormalities
most frequently associated with human cancer are far more likely to
occur in or near the evolutionary breakage hotspots than were less
common types of cancer-associated abnormalities. Researchers theorize
that the rearrangements seen near breakage hotspots may activate genes
that trigger cancer and/or inactivate genes that normally suppress
cancer. However, they emphasize that far more work remains to be done to
clarify the relationship between cancer and the breakage hotspots. One
thing researchers have determined is that the regions immediately
flanking the breakage hotspots contain more genes, on average, than the
rest of the genome.

The team was led by Harris A. Lewin, Ph.D., of the University of
Illinois at Urbana-Champaign, and William J. Murphy, Ph.D., of Texas A&M
University in College Station. Mapping data for the dog genome were
provided by NHGRI's Elaine Ostrander, Ph.D., and Heidi G. Parker, Ph.D.,
along with scientists from the French National Center for Scientific
Research at the University of Rennes. Other study participants were from
the National Cancer Institute, the Genome Institute of Singapore and the
University of California at San Diego.

"Science tells us that the most effective tool we currently have to
understand our own genome is to compare it with the genomes of other
organisms. With each new genome that we sequence, we move closer to
filling the gaps in our knowledge," said Dr. Ostrander, who is chief of
the Cancer Genetics Branch in NHGRI's Division of Intramural Research.

The multi-species comparison published in Science also yielded
surprising results about the rate at which chromosomal evolution occurs.
Based on an analysis that included a computer-generated reconstruction
of the genomes of long-extinct mammals, researchers found the rate of
chromosomal evolution among mammals dramatically accelerated following
the extinction of the dinosaurs about 65 million years ago.

Before the sudden demise of dinosaurs and many other types of animals,
which is thought to have resulted from a massive comet or asteroid
striking Earth, mammals shared fairly similar body plans and also fairly
similar genomes. Researchers speculate that the mass extinction opened
new ecological niches for mammals, spurring their diversification and
the emergence of new mammalian orders. This situation would have
facilitated opportunities for the isolation of mammals into more
distinct breeding groups, speeding the development of species-specific
chromosomes.

"This study has revealed many hidden secrets on the nature and timing of
genome evolution in mammals, and it demonstrates how the study of basic
evolutionary processes can lead to new insights into the origin of human
diseases," said Dr. Lewin, who is director of the Institute of Genomic
Biology at the University of Illinois.

To learn more about the rapidly growing field of comparative genomics,
go to ww.genome.gov/11509542 . The
genomes of a number of organisms have been or are being sequenced by the
large-scale sequencing capacity developed by the Human Genome Project,
which was led in the U.S. by NHGRI and the Department of Energy. A
complete list of organisms and their sequencing status can be viewed at
www.genome.gov/10002154 .

High-resolution photos of dog, cat, cow, rat and other organisms under
study by NHGRI's Large-Scale Sequencing Program are available at
www.genome.gov/10005141 .

NHGRI is one of the 27 institutes and centers at NIH, an agency of the
Department of Health and Human Services. The NHGRI Division of
Intramural Research develops and implements technology to understand,
diagnose and treat genomic and genetic diseases. Additional information
about NHGRI can be found at its Web site, www.genome.gov .

The National Institutes of Health (NIH) - The Nation's Medical Research
Agency - is comprised of 27 Institutes and Centers and is a component of
the U. S. Department of Health and Human Services. It is the primary
Federal agency for conducting and supporting basic, clinical, and
translational medical research, and investigates the causes, treatments,
and cures for both common and rare diseases. For more information about
NIH and its programs, visit www.nih.gov .
Received on Fri 22 Jul 2005 03:18:01 PM PDT