The genetic basis of host specificity in African trypanosomes: why do some species prefer pigs?

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Animal African Trypanosomiasis (AAT) is a disease that places a major burden on livestock farming in sub-Saharan Africa, with impacts on sustainable food production and food security, as well as animal health. The disease is caused by microscopic single-celled parasites (trypanosomes) found in the blood of infected animals and spread by bloodsucking tsetse flies. AAT affects cattle, as well as a range of other animals including pigs, sheep and goats. There is no vaccine against AAT and new drugs are urgently needed to counter increasing resistance to current drugs. AAT has held back development in many African countries, as it severely constrains agricultural productivity through its harmful effects on livestock production and draught animals, with impacts on people's wealth, livelihoods and health. Climate change is likely to exacerbate the impact of AAT through changes in tsetse fly distribution altering the transmission dynamics of the disease. While there has been a major push to eliminate human African trypanosomiasis or sleeping sickness in recent years, research on the parasites that cause AAT, the equivalent livestock disease, has lacked impetus. Several trypanosome species cause AAT and the host range includes both wild and domestic animals, making it a complex disease to combat. Among these trypanosomes, some have a wide host range including cattle, small ruminants and pigs, while others are restricted to pigs. The underlying reasons for restriction to certain livestock hosts are unknown. Here we will investigate whether host specificity has a genetic basis by looking at how pig-restricted trypanosomes originated and diverged over time from those with a broader host range. We will take advantage of recent advances in gene sequencing technology to obtain the complete set of genes - the genome - from each trypanosome. At Bristol, we have a unique collection of trypanosomes isolated over many years of fieldwork in sub-Saharan Africa, which we will use to extract purified DNA for genome sequencing. Each genome will be carefully assembled, allowing us to compare variation in the sequence and numbers of individual genes between trypanosomes. For example, we will be able to determine whether certain genes or variants are associated with adaptation to pig hosts. Not only will this allow us to test hypotheses on how host specificity evolved, but also make predictions about the probability of host switches in the future. The new trypanosome genome sequences we will obtain will also serve as an essential resource for future work on these important parasites, including drug development. Research into AAT is often focused on cattle to the exclusion of other livestock, but pigs and small ruminants also suffer from AAT and these livestock are becoming increasingly important to smallholders as sources of food and wealth. The control of AAT is thus an important task in terms of increasing food production and supply in sub-Saharan Africa, thereby progressing global development goals in sustainable agriculture and food security.