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International Teams Sequence Genomes of Two Blood Parasites

NEW YORK (GenomeWeb News) – A pair of international research teams have sequenced the genomes of two blood flukes, Schistosoma japonicum and S. mansoni.

In the first of these papers, researchers involved in the Schistosoma japonicum Genome Sequencing and Functional Analysis Consortium used whole-genome shotgun sequencing to generate the draft sequence of S. japonicum's 397 million base pair genome.

Meanwhile, another international research team used a similar whole-genome shotgun approach to sequence the 363 million base pair genome of S. mansoni. That group also began trying to harness information in the genome to find schistosome weaknesses, using bioinformatics and a chemogenomic screen to look for fluke proteins that may be vulnerable to existing drugs.

"This genome sequence catapults schistosomiasis research into a new era," Wellcome Trust Sanger Institute researcher Matthew Berriman, lead author on the latter paper, said in a statement. "It provides a foundation for understanding aspects of the parasite's complex biology as well as a vehicle to immediately identify new targets for drug treatment."

Blood flukes — flatworms in the genus Schistosoma — can cause schistosomiasis, a neglected tropical disease characterized by inflammation and damage to blood vessels and/or internal organs. Larval schistosomes are carried by snails and can be transmitted to humans through the skin when they come in contact with contaminated water.

Schistosomiasis affects some 210 million people around the world. It is particularly common in sub-Saharan Africa and parts of South America, the Middle East, and East Asia. Even so, just one main schistosomiasis treatment is available so far — a drug called praziquantel that treats, but doesn't prevent, schistosome infections.

"New drugs and other interventions are badly needed to reduce the impact of a disease that lowers quality of life and slows economic development," National Institute of Allergy and Infectious Disease Director Anthony Fauci said in a statement.

"We need to take advantage of this genetic sequence data to find new and improved ways of coping with this problem that devastates much of the developing world," Michael Gottlieb, associate director of science at the Foundation for the National Institutes of Health, who was not involved in either study, said in a statement.

Indeed, both research teams have already started analyzing the newly deciphered schistosome genomes in an effort to better understand the organisms' biology and find clues about finding new ways to control the flukes.

Analysis of the S. japonicum genome uncovered 13,469 protein-coding genes on eight chromosome pairs. More than a third of the genes appear to have metabolic functions, the researchers reported, though they also found genes involved in processes such as development, locomotion, reproduction, and cellular organization. The repertoire of genes is also providing new insights into how S. japonicum interacts with and exploits host biology.

For their part, Berriman and his team identified 11,809 potential protein-coding genes in the S. mansoni genome. Many of the genes appear to have large introns, they reported, though 3' introns tend to be larger than those at the 5' ends of genes.

Their subsequent analysis of the genome turned up a group of genes with micro-exons — very small exons dispersed in and among normal exons. When the researchers sequenced transcripts representing three of these micro-exon gene families, they found evidence for alternative splicing in these genes based on exon skipping.

Repeat sequences were common in both the S. japonicum and S. mansoni, comprising about 40 percent of each genome.

In their subsequent analyses, Berriman and colleagues used the S. mansoni genome to explore everything from flatworm and animal evolution to the nuts and bolts of S. mansoni biology, including features that make the worms dependent on their hosts.

They also used several approaches — including a bioinformatics search for "metabolic chokepoints" and a chemogenomic screen — to look for schistosome features that could eventually be exploited to prevent schistosome infections and to determine whether existing drugs or compounds might be effective against S. mansoni proteins. For instance, the team identified dozens of S. mansoni transcripts predicted to be vulnerable to existing drugs.

"It is hoped that these and other targets will accelerate drug discovery, generating the much needed new treatments for the control and eradication of schistosomiasis," Berriman and his co-authors wrote.

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