Authors

J A Cotton⁸; S BennuruA GroteR BeechJ C Dunning-HotoppA MhashilkarN NursimuluJ ParkinsonT B NutmanE GhedinM Berriman⁸; S Lustigman ¹ Institute of Parasitology, McGill University, Canada;  ² Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, NIH, United States;  ³ New York Blood Center, United States;  ⁴ New York University, United States;  ⁵ University of Maryland, United States;  ⁶ University of South Florida, United States;  ⁷ University of Toronto, Canada;  ⁸ Wellcome Trust Sanger Institute

Discussion

Human onchocerciasis is a serious neglected tropical disease caused by Onchocerca volvulus, leading to blindness and chronic disability. The development of new drugs and vaccines depend on better knowledge of parasite biology. We have assembled a high-quality reference genome for O. volvulus and its Wolbachia endosymbiont, reconstructing essentially complete chromosomes of the parasite. We describe large-scale patterns in genome structure to those known in C. elegans. We also investigate the gene complement of this key human pathogen in the context of other filarial genomes, identifying a number of gene family expansions that may underpin key aspects of parasite biology. Transcriptomic and proteomic data shows that some of these duplicated genes are expressed specifically in particular parts of the parasite's complex lifecycle. We use the genome annotation as a substrate for an in-silico reconstruction of the metabolism of Onchocerca volvulus and other filaria, and use this to identify key essential reactions that could represent valuable drug targets. In particular, differences in purine metabolism suggest that purine-nucleotide phosphorylase could represent a target for chemotherapy specifically killing Onchocerca over Loa loa, an important constraint on the use of ivermectin, the main current drug treatment. This illustrates how the data we have generated could serve to underpin ongoing efforts to control onchocerciasis.