Genome sequencing white paper for the black fly disease vectors Simulium sp.

C. Brockhouse, A. Papanicolaou, R. Post, D. Boakye, E.W. Cupp, M. Pfrender, J.K. Colbourne
Broad Institute

Black flies (Diptera: Simuliidae) are the second most medically-important group of arthropod pest species affecting human health and are now the most important group of disease vectors and pest species lacking a representative genome project. The family also occupies a critical taxonomic placement in the sub-order Nematocera, making it an important out-group for genomic studies in mosquitoes and other important hematophagous Diptera associated with leishmaniasis and viral encephalitis. Simulium species are the sole vectors for the human filarial parasite Onchocerca volvulus, the causative agent of onchocerciasis, or river blindness. River blindness is a scourge of some of the poorest regions of the world, affecting 39 million people worldwide. Historically, it has been the second most important infectious cause of blindness (after trachoma) and the second most important disease in terms of overall socio-economic impact, eclipsed only by polio.

The socio-economic impact of onchocerciasis has been recognized by the international community, which has supported a number of large control programs to reduce the impact of the disease on the afflicted populations. For example, the Onchocerciasis Control Programme in West Africa, a program that focused primarily upon the control of S. damnosum in 13 countries of Africa was active from 1975-2002, and spent more than $565 million over its lifetime. The tradition of interest in onchocerciasis by the international community continues to this day, with ongoing programs in Africa (the African Programme for Onchocerciasis Control (APOC)) and Latin America (the Onchocerciasis Elimination Program in the Americas (OEPA)) spending millions to control the disease.

Until recently, it was felt that onchocerciasis could not be eliminated using the currently available tools, which rely primarily upon mass distribution of the anti-helminthic drug ivermectin. However, recent studies have suggested that long term treatment with ivermectin has dramatic effects on fertility of the adult female parasites. This finding has resulted in a paradigm shift in the field of onchocerciasis control, moving from a focus upon control in Africa towards elimination. The strategy to accomplish elimination involves delineating isolated foci of the infection, and eliminating the infection sequentially in these isolated foci, eventually resulting in continent wide elimination of the parasite. For this strategy to be successful, it is first necessary to delineate these isolated foci or transmission zones. In Africa, the major vector Simulium damnosum s.l., is known to be capable of long distance migration. The extent of the transmission zones will thus likely be determined by vector movement throughout most of Africa. To delineate these transmission zones, polymorphic markers capable of distinguishing populations and of determining effective population sizes are critically needed. Genome sequences of the African vectors for onchocerciasis will provide a rich source of such markers.

This document proposes the sequencing of 11 Simulium genomes (genome size smaller than 187 Mb), including both disease vectors and non-vector species. For critical vector species and populations, we simultaneously propose re-sequencing of 50 individuals per species, to identify polymorphisms for vitally needed population genetic studies, and to identify genes involved in vectorial capacity and the ability to colonize. The availability of multiple black fly genomes will provide an epidemiological and genetic framework delimiting the spatial distribution of vector sibling species in areas where onchocerciasis control is on-going, greatly aid the identification of promising species-specific genetic control targets, provide a frame-work for ecological genomic studies, and give an entrée into detailed gene regulation analysis in an otherwise intractable group of insects.