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Researchers Search for Clues to Roundworm Infections in Pig Parasite Genome

NEW YORK (GenomeWeb News) – An international team reported online today in Nature that it has sequenced the draft genome of Ascaris suum, a parasitic roundworm that infects pigs.

The group, led by researchers from Australia and China, generated a 273 million base genome sequence for A. suum. By comparing the genome with sequences from other parasitic and non-parasitic roundworms, including the model organism Caenorhabditis elegans, they were able to find genetic features that may contribute to parasitism by the A. suum and a closely related human parasite A. lumbricoides, including hundreds of molecules that seem to be secreted by the pig parasite to help it break down and invade animal tissues and resist host immunity.

When they focused on predicted parasitic worm proteins resembling indispensable proteins from C. elegans and Drosophila, meanwhile, the team found five potential drug targets in A. suum.

"From the genome sequence we have identified five high-priority drug targets that are likely to be relevant for many other parasitic worms," University of Melbourne veterinary science researcher, Aaron Jex, the study's first author, said in a statement. "New treatments are urgently needed and genome-guided drug target discovery is ideal for identifying targets that selectively kill the parasite and not the host."

Ascaris worms infect more than a billion people around the world, many in developing countries in Asia, Africa, and Latin America, the researchers noted. By setting up shop in the human intestine, the worm can impair nutrient absorption and create blockages in the intestine, leading to physical and cognitive impairment and sometimes death. Ascariasis in animals can have detrimental social and economic impacts too, they explained, affecting food production and leading to large losses for pig farmers.

For the current study, researchers took advantage of this pig parasitism, studying larval and adult forms of the swine-infecting roundworm A. suum collected from pigs with naturally acquired infections.

Using the Illumina HiSeq 2000, the team sequenced nearly 273 million bases of the A. suum draft genome to a depth of around 80 times. They also used the Illumina platform to do RNA sequencing on adult worms and worm larvae from various pig tissues.

Overall, they found that the A. suum genome is far less repeat rich than most other animal genomes characterized to date: just 4.4 percent of the genome sequence appears to be comprised of repeats. In their analyses of the genome, the researchers identified sequences from nearly two-dozen retrotransposon families and eight DNA transposon families.

Additional analyses suggest the genome houses 255 transfer RNA genes and an estimated 18,542 protein-coding genes. Indeed, the researchers' transcriptome data contained sequences for nearly 15,000 of these predicted genes.

Comparisons with the animal parasite Brugia malayi, the plant parasite Meloidogyne hapla, and the free-living roundworms C. elegans and Pristionchus pacificus indicated that more than 78 percent of A. suum's genes have homologues in at least one other roundworm.

While it shared homology with each of the roundworms tested, though, the A. suum genome had the highest overall genome synteny with the other animal parasite, B. malayi.

Among the 13,500 or so A. suum genes for which functional information was available were genes coding for hundreds of enzymes suspected of helping A. suum to infiltrate and break down host tissues during infection or give its host's immune system the slip. Some of these proteins appear to belong to the worm's "secretome," a set of the more than 750 molecules suspected of being secreted by the worm while interacting with its host.

Other genes that were identified appear to code for receptor and ion channel genes and proteins suspected of contributing to the worm's reproduction and development.

RNA sequence data, meanwhile, offered clues to the transcriptional patterns found in A. suum worms at various developmental stages and in different host tissues as the worms make their way to the host small intestine. From the RNA sequences generated so far, researchers also found nearly 164,000 coding SNPs in the A. suum genome.

Finally, when they looked for A. suum proteins with homologues that are essential for the growth of C. elegans or fruit flies, the researchers found five proteins produced by the parasite that may be especially vulnerable to targeted treatment.

By mining the genome further, researchers hope to uncover other clues about diagnosing, preventing, and treating infections caused by A. suum and the human parasite A. lumbricoides.

"This genome provides a comprehensive resource of new and urgently needed interventions (drugs, vaccines, and diagnostic tests) against ascariasis and other nematodiases," the researchers wrote.

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