Wednesday, Oct. 2, 2002 -- Genome sequences of Plasmodium
falciparum, the most lethal malaria-causing parasite, and Anopheles gambiae, a
mosquito that transmits the parasite to humans, are now complete, two
international research teams announced today.
The simultaneous publication in Science of
the Anopheles genome and in Nature of the Plasmodium genome was marked by press
conferences held in Washington, DC, and London.
"The
sequencing of both P. falciparum and its insect vector heralds a new era in the
fight against malaria. When joined with information we have about the human
genome, a much fuller understanding of this disease and its transmission is now
possible," says Anthony S. Fauci, M.D., director of the National Institute
of Allergy and Infectious Diseases (NIAID).
"NIAID
is proud to have contributed to this extraordinary scientific achievement, which
will speed efforts to investigate and develop control strategies for this
devastating disease."
The
medical, social and economic ravages of malaria are most keenly felt in Africa,
where 90 percent of the up to 2.7 million annual deaths worldwide from the
disease occur. Most victims are children less than 5 years old; on average, a
child succumbs to malaria every 30 seconds.
Malaria
causes cycles of fever and chills that accompany cyclical destruction of
parasite-infected red blood cells. Debilitating and life-threatening
complications of malaria include severe anemia, cerebral malaria, and
respiratory distress.
The
disease is caused by single-celled parasites of the genus Plasmodium, which are
transmitted from person to person through the bite of an infected mosquito.
The
menace posed by malaria is increasing with the spread of drug-resistant parasite
strains and insecticide-resistant mosquitoes. No vaccine exists.
The
sequencing of P. falciparum resulted from an international collaboration
established in 1996. Besides NIAID, consortium support came from the Wellcome
Trust, the Burroughs Wellcome Fund and the U.S. Department of Defense.
Sequencers worked at The Institute for Genomic Research (TIGR) in Rockville, MD,
the Stanford Genome Center in Palo Alto, CA, and the Wellcome Trust Sanger
Institute in the United Kingdom. The lead investigator, Malcolm Gardner, Ph.D.,
of TIGR, co-authored the Nature paper with 44 researchers working in sites in
the United States, the United Kingdom and Australia.
Researchers
overcame significant technical challenges on the way to this accomplishment.
Perhaps because of its unusual composition, Plasmodium's genetic material cannot
be separated into a mixture of long, medium, and short lengths.
Rather,
the parasite's DNA breaks up into very short lengths only. Placing such tiny
strips back into their original sequence is difficult, just as repairing a vase
that has smashed into hundreds of bits is harder than fixing one broken into a
few large pieces.
"This
detailed map of the parasite's 5,300 genes and their predicted functions is a
milestone in malaria research. The information it provides will enable
investigators to design anti-malarial drugs targeted precisely to areas of
genetic vulnerability," says Michael Gottlieb, Ph.D., chief of NIAID's
parasitology and international programs branch.
In
1999, NIAID joined the Anopheles Gambiae Genome Consortium (AGGC) to accelerate
sequencing of Anopheles' 14,000 genes.
Sequencing
was performed at Genoscope with funds from the French government and at the
Celera Genomics Group in Rockville, MD. Other institutions contributing to the
effort include World Health Organization's Special Program of Research on
Tropical Diseases; Germany's European Molecular Biology Laboratory; the
Institute of Molecular Biology and Biotechnology in Crete; the Institut Pasteur
in Paris; TIGR; and the universities of Iowa, Rome, Notre Dame, and Texas
A&M.
In
August 2001, NIAID expanded its support for Anopheles genome sequencing with a
$9 million award to Celera Genomics Group of Rockville, MD. Celera's Robert A.
Holt, Ph.D., heads a list of 123 authors on the Science paper, submitted on
behalf of the AGGC.
Before
this week's publications, significant amounts of sequence data produced by both
teams had been disseminated through publicly accessible databases. For example,
P. falciparum genes were identified that allow the parasite to avoid detection
by human immune response cells. Other genes involved in parasite metabolism have
no counterparts in humans. Inhibitors of those genes' products could be
developed into anti-malarial drugs.
Information
from the Anopheles genome is giving researchers new insights into mosquito
physiology and behavior, including the insect's ability to digest blood and its
choice of humans as a blood source.
Scientists
can now begin to determine how Anopheles reacts, at a molecular level, to
infection with the Plasmodium parasite. Ultimately, such a detailed
understanding of host-parasite interactions could improve mosquito control
efforts.
With
the triad of genomes now complete, investigators have essentially all the
genetic information they need to understand the complexity of the parasite's
life cycle in mosquitoes and humans, notes Dr. Gottlieb. "We are hopeful
that this wealth of information will translate into new drugs, vaccines, and
insecticides that will more effectively control malaria and, ultimately, lift a
burden of suffering from millions," he adds.
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NIAID's
comprehensive program of research on malaria, which began 50 years ago, is
conducted at its laboratories in Bethesda, MD, in dozens of institutions
throughout the United States, and through collaboration with scientists from
countries where malaria is endemic, such as Mali, Cameroon, Ghana, Thailand,
Indonesia, and Brazil. The Institute was also founding member of the
Multilateral Initiative on Malaria, which emphasizes strengthening research
capacity in Africa. For more information on NIAID's malaria research and
research support, visit http://www.niaid.nih.gov/dmid/malaria.
References:
M. J. Gardner et al. Genome sequence of the human malaria parasite Plasmodium
falciparum. Nature 419: 498-511. (2002).
RA
Holt et al. The genome sequence of the malaria mosquito Anopheles gambiae.
Science 297: 129-49 (2002).
NIAID
is a component of the National Institutes of Health (NIH). NIAID supports basic
and applied research to prevent, diagnose, and treat infectious and
immune-mediated illnesses, including HIV/AIDS and other sexually transmitted
diseases, illness from potential agents of bioterrorism, tuberculosis, malaria,
autoimmune disorders, asthma and allergies.
The National Institute of
Allergy and Infectious Diseases is a component of the National Institutes of
Health, U.S. Department of Health and Human Services