An international team of researchers led by the Yale School of Public Health has successfully sequenced the genetic code of the tsetse fly, opening the door to scientific breakthroughs that could reduce or end the scourge of African sleeping sickness in sub-Saharan Africa.
It took nearly 10 years and involved more than 140 scientists from numerous countries to map the genome of the fly (Glossina morsitans). Tsetse flies are the sole insect vectors of a disease that threatens the health of millions of people and devastates livestock herds. The study is published today in the journal Science.
The genetic blueprint will provide researchers with the codes for the proteins that make up the tsetse fly. It is essentially a “parts list” of what the organism, which is slightly larger than a common housefly, is made from.
“This is a major milestone for the tsetse research community and represents years of hard work by scientists.” said Geoffrey M. Attardo, a research scientist at the School of Public Health and the paper’s lead author. “Our hope is that this resource will facilitate functional research and be an ongoing contribution to the vector biology community. The final product is a reflection of the wonderful community of tsetse researchers from around the globe whose contributions made this project a reality. I feel lucky to have been a part of it.”
Access to the blueprint is expected to accelerate research into the tsetse fly’s unique biology and allow for the development of improved tsetse control methods as well as the development of new control strategies.
While drugs do exist to combat sleeping sickness, they are expensive, have many undesirable side effects and are difficult to administer in wide swaths of rural Africa where the disease is most pronounced. Left untreated, sleeping sickness is 100 percent fatal.
The disease in animals hinders agricultural practices and restricts economic development as the disease destroys the livestock upon which families and farmers depend. The disease is pronounced in countries such as Uganda, the Democratic Republic of the Congo and Sudan but its range extends to more than 30 other countries in the region. Due to international efforts, the disease numbers have come down in much of the sub-Sahara to endemic levels, but hotspots remain and armed conflict can potentially cause is to re-emerge.
The researchers had to overcome numerous challenges—technical, biological and economic—in order to achieve the complete sequence. As with most genome projects the researchers had to limit their analysis to a single genetic line in order to improve the assembly of small fragments of sequence data (thousands of letters of code) into large scaffolds (millions of letters of code). This became an issue as only a small amount of genetic material is obtainable from each fly and one tsetse female, unlike other insects, gives birth to very few offspring. Sequencing technology also has improved dramatically over the life of the project. When the effort began, the prevailing method was much more labor intensive, more costly, required more material and yielded poorer results. Recent technologies have improved all aspects of this process and accelerated progress to the finish line.
School of Public Health Professor Serap Aksoy helped initiate the collaborative research project in the early 2000s when she and a small group of other researchers concluded that progress against the disease and new tsetse-based control opportunities would be stymied unless the biological and chemical underpinnings of the organism were completely understood. The consortium was initiated with seed funding from the World Health Organization.
“We are very happy to reach the finish line finally,” Aksoy said. Along with the genetic map, the community of researchers produced eight research papers that are released this week in PLOS wide journals. These papers describe some of the low-hanging fruit with translational implications. “Working closely with colleagues at the Wellcome Trust Sanger Institute (where the genome was sequenced and assembled) as well as the many European and African researchers and students who participated in the multiple annotation workshops we organized in South Africa, Cambridge and Kenya were memorable experiences for me. Our hope is that tsetse research will now enjoy broader participation from the vector community and lead to improved and/or novel methods to eliminate disease.”
While the tsetse fly is not the first insect to have its genome mapped, it completion is a significant landmark in the fight against vector-borne diseases such as sleeping sickness and signals the length to which researchers will go in order to find viable solutions that improve public health.
The tsetse fly project cost approximately $10 million and was funded over the years from multiple public and private sources. The tsetse fly genome contains approximately 366 million letters of code, which is equivalent to about 10 percent of the size of the human genome.
Dean Paul Cleary praised the accomplishment and noted that it only could have happened with close collaboration between multiple individuals and institutions.
“The sequencing of the genetic code of the tsetse fly is not only a major scientific achievement that could have a huge impact on our ability to control the spread of trypanosomiasis, but also is a testament to the power of collaborative research projects that involve teams of scientists from different institutions,” he said. “This could not have been achieved by a single research team and illustrates the need for, and incredible potential of, interdisciplinary team science.”
Beyond disease control, the genome wide map of the tsetse fly will also be an important resource for the understanding of evolutionary biology. Tsetse flies are unique from almost all other insects in that they have developed an essential relationship with a bacterial symbiont for multiple aspects of their biology, they give birth to live young and they feed their offspring through lactation.
Data from the project is currently being hosted by Vectorbase (www.vectorbase.com) and is publicly available for download or for direct analysis on the website using a comprehensive set of browsing, search and analysis tools.
In addition to Attardo and Aksoy, other Yale researchers involved in the project include present and past members of the group including, Joshua Benoit, Brian Weiss, Jingwen Wang, Uzma Alam, Corey Brelsfoard, Michelle Maltz, Xin Zhao, Aurelien Vigneron, Erich Tellaria and Veronika Michalkova.