Tsetse fly genome sequenced with help from UWC-SANBI

The International Glossina Genome Initiative (IGGI), including scientists at the University of the Western Cape’s South African National Bioinformatics Institute (SANBI), led by Professor Alan Christoffels, have concluded a ten-year project on the genome of the tsetse fly (Glossina morsitans morsitans). Understanding the genomic structure and behavior of the tsetse fly is pivotal to treating sleeping sickness, a disease that affects about 70 million people in sub-Saharan Africa, where the tsetse fly is most commonly found.

African sleeping sickness in humans (Human African Trypanosomias – HAT) is a dreadful disease to contract, and one that more often than not results in death. ‘Sleeping sickness’, the colloquial name for HAT, originates from observations of how the disease affects the infected person’s sleep pattern. The saliva of the tsetse fly contains parasitic trypanosomes. When the human host is bitten, the host’s blood is infected with trypanosomes. There is no known vaccine to prevent the spread of infected blood throughout the bloodstream. The early stages of the parasite infection in the host leads to fever, headaches, and joint pain. If undetected, it attacks the lymphatic system where swelling of the lymph nodes at the back of the neck are prominent. Finally, the central nervous system is assailed by the infection once its crosses the blood-brain barrier.

When the host is at this stage of infection, the sleep-cycle is affected. The patient is confused and disoriented and experiences a disrupted sleep pattern, with long sleep cycles by day and fragmented periods of wakefulness and delirium at night. There is no medically viable course of treatment.

Until recently, public health drives were concentrated on preventing new infections in the absence of a vaccine. Efforts to prevent new infections in areas commonly afflicted by HAT have focused on using insect repellents and wearing appropriately protective clothing to avoid being bitten by the tsetse fly.

Ten years ago, scientists formed the International Glossina Genome Initiative  (IGGI), with the view that understanding the biology of the fly may be an important step towards preventing the spread of HAT.

The aim of the IGGI consortium was clear: unveiling the physiological working of the fly could present the opportunity for biomedical researchers to develop new vector control strategies to limit the spread of sleeping sickness.

The tsetse fly has a unique physiognomy, physiology, and behavioural traits – most notably as a vector for Human African Trypanosomiasis. This is not new to the researchers. However, the primary focus of the IGGI consortium was to sequence the entire tsetse fly - a 366 million base pair genome. The key exercise here was to identify and annotate (describe) the genes within the genome sequence.  The availability of this genomic data and its concomitant knowledge – including knowledge of the tsetse fly’s vision, olfaction, immune and reproductive physiology – provides an unparalleled opportunity to transform tsetse fly research and associated disease control practices.

Tsetse flies are known for their unique biology: they feed exclusively on vertebrate blood; they give birth to live young (one at a time); they provide nutrition to their young by lactation, and they have formed complex relationships with no less than three different symbiotic bacteria. In addition, there are no doubt several mysteries that need to be solved – the genome holds information for which nobody has yet identified functions.

The analysis of the genome has assisted in revealing the basic biology of the fly on a fundamental level. For example, identifying genes that produce proteins involved with vision or smell allow researchers to better understand what may attract or repel tsetse flies, and thus trap them or drive them away.

A particular area of interest has been tsetse mechanisms that eliminate parasites in the midgut. This is of both basic and applied research interest, since the ability to engineer greater resistance in flies could solve the problem of disease transmission.

The IGGI consortium encompasses and is driven by over 140 scientists from a range of research areas at different institutions. It is truly an inter- and multi-disciplinary research project that includes researchers from, inter alia, the South African National Bioinformatics Institute, the International Centre for Insect Physiology and Entomology (ICIPE) in Kenya, the Yale School of Public Health in the United States, the European Bioinformatics Institute (EBI) and the Wellcome Trust Sanger Centre in England, and the Liverpool School of Tropical Medicine in England.

The African component of the IGGI consortium comprised over 40 experienced African researchers.  They all were involved in multiple group annotations held in South Africa, Kenya, and Uganda. A hallmark of this consortium, however, is that African and Africa-based researchers played a decisive leadership role in the research.

According to Professor Christoffels: “All of the activities were directed at supporting genomics research on the African continent. We have developed partnerships with researchers across the African continent over the course of the project. International genome projects are often directed at the primary goal of sequencing the genome and annotating the genes. Besides the scientific findings, this programme has demonstrated the value of genomics training in the context of a DNA sequencing project.”

For Professor Christoffels and his African counterparts, human capacity development was a crucial factor of the success of their scientific endeavour.

To this end, SANBI – which has previously been involved in major international genomics research, including analysing the coelacanth genome – invested heavily in computer-based training pertaining to the analysis of the tsetse fly genomic data. Bioinformatics training at SANBI included: the analysis of the olfactory genes and the iron-metabolism genes; the examination of characteristics that control the ‘on/off’ switch of the genome; the identification of DNA that repeats itself multiple times in the genome; and, the description of the location of particular genes in the genome.

Six PhD students conducted their research on this tsetse project, graduating from the University of the Western Cape, of which SANBI is an affiliate.  Two PhD students still conducting research on the tsetse fly are concurrently supervised at SANBI and ICIPE in Kenya. This collaboration is a fine example of experienced scholars who are confident of their collaborative relationships and of African institutes of scientific research sharing their distinct expertise.

The results of this ten-year collaboration appears on 25 April 2014 in the journal entitled Science. A collection of satellite research papers will appear concurrently in the open access journal, PLoS Neglected Tropical Diseases, in which various aspects and functions of tsetse fly genes will be discussed further.  

Trypanosomiasis does not only affect humans. It affects animals too, particularly cattle. Continued research into various tsetse fly species as they infect cattle via the trypanosome will also be of benefit to the agricultural communities of sub-Saharan countries, and by extension, the broader SADC commercial agricultural economy.