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1.
Nat Genet ; 48(3): 299-307, 2016 Mar.
Article En | MEDLINE | ID: mdl-26829753

Soil-transmitted nematodes, including the Strongyloides genus, cause one of the most prevalent neglected tropical diseases. Here we compare the genomes of four Strongyloides species, including the human pathogen Strongyloides stercoralis, and their close relatives that are facultatively parasitic (Parastrongyloides trichosuri) and free-living (Rhabditophanes sp. KR3021). A significant paralogous expansion of key gene families--families encoding astacin-like and SCP/TAPS proteins--is associated with the evolution of parasitism in this clade. Exploiting the unique Strongyloides life cycle, we compare the transcriptomes of the parasitic and free-living stages and find that these same gene families are upregulated in the parasitic stages, underscoring their role in nematode parasitism.


Genomics , Strongyloides/genetics , Strongyloidiasis/genetics , Symbiosis/genetics , Animals , Biological Evolution , Humans , Life Cycle Stages/genetics , Strongyloides/pathogenicity , Strongyloidiasis/parasitology , Transcriptome/genetics
2.
Genome Biol ; 15(11): 510, 2014.
Article En | MEDLINE | ID: mdl-25413302

BACKGROUND: Sparganosis is an infection with a larval Diphyllobothriidea tapeworm. From a rare cerebral case presented at a clinic in the UK, DNA was recovered from a biopsy sample and used to determine the causative species as Spirometra erinaceieuropaei through sequencing of the cox1 gene. From the same DNA, we have produced a draft genome, the first of its kind for this species, and used it to perform a comparative genomics analysis and to investigate known and potential tapeworm drug targets in this tapeworm. RESULTS: The 1.26 Gb draft genome of S. erinaceieuropaei is currently the largest reported for any flatworm. Through investigation of ß-tubulin genes, we predict that S. erinaceieuropaei larvae are insensitive to the tapeworm drug albendazole. We find that many putative tapeworm drug targets are also present in S. erinaceieuropaei, allowing possible cross application of new drugs. In comparison to other sequenced tapeworm species we observe expansion of protease classes, and of Kuntiz-type protease inhibitors. Expanded gene families in this tapeworm also include those that are involved in processes that add post-translational diversity to the protein landscape, intracellular transport, transcriptional regulation and detoxification. CONCLUSIONS: The S. erinaceieuropaei genome begins to give us insight into an order of tapeworms previously uncharacterized at the genome-wide level. From a single clinical case we have begun to sketch a picture of the characteristics of these organisms. Finally, our work represents a significant technological achievement as we present a draft genome sequence of a rare tapeworm, and from a small amount of starting material.


Diphyllobothrium/genetics , Genome , Sparganosis/genetics , Spirometra/genetics , Animals , Base Sequence , Biopsy , Brain/parasitology , Brain/pathology , High-Throughput Nucleotide Sequencing , Humans , Sparganosis/parasitology , Spirometra/parasitology , United Kingdom
3.
Nat Genet ; 46(7): 693-700, 2014 Jul.
Article En | MEDLINE | ID: mdl-24929830

Whipworms are common soil-transmitted helminths that cause debilitating chronic infections in man. These nematodes are only distantly related to Caenorhabditis elegans and have evolved to occupy an unusual niche, tunneling through epithelial cells of the large intestine. We report here the whole-genome sequences of the human-infective Trichuris trichiura and the mouse laboratory model Trichuris muris. On the basis of whole-transcriptome analyses, we identify many genes that are expressed in a sex- or life stage-specific manner and characterize the transcriptional landscape of a morphological region with unique biological adaptations, namely, bacillary band and stichosome, found only in whipworms and related parasites. Using RNA sequencing data from whipworm-infected mice, we describe the regulated T helper 1 (TH1)-like immune response of the chronically infected cecum in unprecedented detail. In silico screening identified numerous new potential drug targets against trichuriasis. Together, these genomes and associated functional data elucidate key aspects of the molecular host-parasite interactions that define chronic whipworm infection.


Gene Expression Profiling , Genome, Helminth , Host-Parasite Interactions/genetics , Host-Parasite Interactions/immunology , Th1 Cells/immunology , Trichuriasis/genetics , Trichuris/genetics , Animals , Humans , Intestines/parasitology , Male , Mice , Mice, Inbred C57BL , Phylogeny , Species Specificity , Trichuriasis/immunology , Trichuriasis/parasitology , Trichuris/immunology
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