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Researchers Sequence Genome of Trichinosis Parasite

By a GenomeWeb staff reporter

NEW YORK (GenomeWeb News) – In a paper appearing online yesterday in Nature Genetics, a Washington University-led research team reported that it has sequenced the genome of Trichinella spiralis, the parasitic nematode behind most cases of the food borne illness trichinellosis, also known as trichinosis.

Through comparative genomic analyses, including comparisons with the non-parasitic nematode Caenorhabditis elegans, the group identified genetic and genomic features that seem to be shared across nematode species, as well as traits found only in nematodes with parasitic lifestyles. Given their findings so far, those involved in the research say such comparative approaches may eventually offer clues to combating T. spiralis and related pathogens.

"This provides opportunities for scientists to dig deeper into the distinctive features of parasitic nematodes that can be targeted with new drugs," lead author Makedonka Mitreva, a genetics researchers with Washington University's Genome Center, said in a statement. "If those drugs target molecular features unique to parasitic worms, it is more likely the side effects of those drugs will be minimal in humans."

Larvae of parasites in the Trichinella genus infect animal tissue and then mature into adults in the intestine of other animals that consume this infected flesh, the researchers explained. There, the parasites mate, spawning larvae that move into the new host's muscle tissue, where the parasites can cause trichinosis.

The disease, which is typically associated with eating raw or under-cooked pork or wild game meat, can lead to chronic pain and, in some cases, serious complications such as myocarditis and encephalitis.

"Once the worms invade the muscle, drugs are less effective," Mitreva said. "While the disease is rarely deadly, patients often live for months or years with chronic muscle pain and fatigue until the worms eventually die."

Using whole-genome shotgun and map-assisted sequencing strategies, Mitreva and her co-workers sequenced libraries made using DNA from a T. spiralis strain called ISS 195. In the process, they generated sequence covering about 90 percent of the worm's 64 million base genome to around 35 times coverage.

During their subsequent analyses, the researchers found 15,808 predicted protein-coding genes in the T. spiralis genome — several thousand fewer than reported for C. elegans.

The T. spiralis and C. elegans genomes have comparable gene density and repeat patterns, the researchers noted, despite the fact that the worms diverged from one another some 600 to 700 million years ago.

Still, many of T. spiralis genes are distinct from those found in C. elegans or other organisms: about 45 percent of genes detected in the T. spiralis genome had not been previously found in any other species.

By bringing in data on two more nematode species, as well as the fruit fly Drosophila melanogaster and yeast Saccharomyces cerevisiae, the team homed in on 274 gene families that are shared between the nematodes but not found in non-nematodes. And compared with other organisms, they explained, the nematode lineage seems to be particularly prone to intra-chromosomal rearrangements.

Meanwhile, when they compared parasitic and non-parasitic nematodes with one another, the researchers tracked down 64 gene families that are found only in the parasitic worms. Their comparison also suggests that the loss of protein families has outpaced the birth of new ones in the parasitic nematodes — a pattern not detected in non-parasitic members of the group.

Given the identification of these sorts of parasite-specific genome features, those involved in the study are optimistic that comparative genomic approaches will provide resources for those trying to come up with new treatments for trichinosis and other plant and animal diseases caused by parasitic nematodes.

"By comparing nematode genomes, we have identified key molecular features that distinguish parasitic nematodes, raising the prospect that a single targeted drug may be effective against multiple species," senior author Richard Wilson, director of the Washington University Genome Center, said in a statement.