[ RadSafe ] MULTI-SPECIES GENOME COMPARISON SHEDS NEW LIGHT ON EVOLUTIONA RY PROCESSES, CANCER MUTATIONS

Mon Oct 3 13:25:13 CDT 2005

>From another list server.  "In addition to their
evolutionary implications, chromosomal translocations
are known to contribute to the development or
progression of many types of cancer."  It would help
to explain why radiation is a weak carcinogen as the
effects only occur at "hot spots."

-----Original Message-----
From: NIH OLIB (NIH/OD) 
Sent: Thursday, July 21, 2005 2:11 PM
To: List NIHPRESS
Subject: MULTI-SPECIES GENOME COMPARISON SHEDS NEW
LIGHT ON EVOLUTIONARY P ROCESSES, CANCER MUTATIONS

U.S. Department of Health and Human Services 
NATIONAL INSTITUTES OF HEALTH 
NIH News 
National Human Genome Research Institute (NHGRI)   
http://www.genome.gov/

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.

##

This NIH News Release is available online at:
http://www.nih.gov/news/pr/jul2005/nhgri-21.htm.

+++++++++++++++++++
"Anyone who has never made a mistake has never tired anything new."
-- Albert Einstein

-- John
John Jacobus, MS
Certified Health Physicist
e-mail:  crispy_bird at yahoo.com

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