Deadly Parasites Have Common Genetic Core
THE INSTITUTE FOR GENOMIC RESEARCH
Deadly Parasites Have Common Genetic Core;
Studies May Help Target New Drugs to Fight Them
Scientists decipher, compare the genomes of parasites that threaten
half a billion people, causing Chagas disease, Sleeping Sickness and
Leishmaniasis
One parasite causes a deadly sleeping sickness in Africa. The second
damages the internal organs of millions of Latin Americans. The
third causes terrible lesions on the face or limbs of victims from
Brazil to India.
The three parasites the culprits behind African sleeping sickness,
Chagas disease and leishmaniasis cause markedly varying diseases
and are carried by different insect vectors. But scientists have
found that the pathogens have a core of about 6,200 conserved genes.
Their genetic similarities far outweigh their differences.
"This common core of genes is extremely important because it may
provide targets for a new generation of drugs that might fight all
three parasites, which threaten millions of people worldwide," says
Najib El-Sayed, the first author of two of the parasite papers that
appear in the July 15 issue of Science and senior author of a third
paper. "At the moment, there are no vaccines and only a few
inadequate drugs to fight these devastating and neglected diseases."
El-Sayed is a molecular biologist at The Institute for Genomic
Research (TIGR), of Rockville, Maryland, which conducted the genome
sequencing and analysis along with scientists at the Wellcome Trust
Sanger Institute in Hinxton, U.K.; the Seattle Biomedical Research
Institute (SBRI); and the Karolinska Institutet, in Stockholm,
Sweden.
The Science issue includes several related papers, including genome
studies of Trypanosoma cruzi, which causes Chagas disease;
Trypanosoma brucei, which causes African trypanosomiasis, also known
as sleeping sickness; and Leishmania major, which causes the skin
disease leishmaniasis and an internal disease known as kala azar.
Another paper compares the three related genomes.
By determining the shared genes and focusing on those that differ,
the comparative study sheds important new light on the genetic basis
for the differences between the parasites including how they
infect people, how they cause human disease, and why they are
carried by different insects. (T. cruzi is carried by blood-sucking
triatomine insects; T. brucei by the tsetse flies; and L. major by
sand flies.)
The comparison found dozens of genes found in all three parasites
that may have been acquired from bacteria through lateral gene
transfer. In addition, studies of the parasites' Variant Surface
Glycoproteins (VSGs) found T. brucei to have the most complex
genetic apparatus for avoiding host immune systems and, at the same
time, to be the most dependent of the parasites on the host's
metabolism. Scientists also discovered that many of the genes
specific to each species are found in so-called sub-telomeric
regions near the ends of chromosomes areas where the genome tends
to be more changeable.
An important finding in the T. cruzi genome study was the discovery
of a novel and large set of 1,300 genes (called the "mucin-
associated surface protein," or MASP, genes) that may play a role in
the parasite's evasion of the human immune system or in its ability
to survive in the variety of hosts that it infects.
The T. cruzi project was funded by the National Institute of Allergy
and Infectious Diseases (NIAID), part of the U.S. National
Institutes of Health. The major funders of the T. brucei and L.
major genome projects were The Wellcome Trust and the NIAID.
Matthew Berriman of Sanger, the first author of the T. brucei genome
paper, predicts that the genome sequences will help advance research
into diseases that have been "neglected" in the past. "Genome
sequences allow ideas to be tested and more quickly turned into
reality," Berriman says. "The basic building blocks of all three
parasites are now known."
Peter J. Myler of SBRI, who shared the first authorship with El-
Sayed on two of the papers, says: "Now that the genes of these
parasites are mapped out, it's much easier to identify genes that
are critical for parasite survival. Genes encoding proteins that are
involved in critical biological processes often serve as drug
targets."
Much of the world's population in tropical and sub-tropical areas is
at risk of contracting one or more of the diseases. Chagas disease
which may have infected Charles Darwin infects as many as 18
million people and threatens about 100 million others in Latin
America, according to the World Health Organization. African
sleeping sickness (trypanosomiasis) infects between 300,000 and
500,000 persons and threatens more than 60 million people in 36
countries in sub-Saharan Africa. Leishmaniasis (which also can be
caused
by related parasites) is endemic in 88 countries and may threaten
as many as 300 million people.
*
* *
The Institute for Genomic Research (TIGR), which sequenced the first
complete genome of a free-living organism in 1995, is a not-for-
profit research institute based in Rockville, Maryland. TIGR
conducts research involving the structural, functional, and
comparative analysis of genomes and gene products in viruses,
bacteria, archaea, and eukaryotes.
[In addition to his faculty position at TIGR, Dr. El-Sayed also
holds an appointment in the microbiology and tropical medicine
department at the George Washington University School of Medicine in
Washington, D.C.]
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