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

非洲动物锥虫病是一种给撒哈拉以南非洲的畜牧业造成重大负担的疾病，对可持续粮食生产和粮食安全以及动物健康造成影响。这种疾病是由感染动物血液中发现的微小单细胞寄生虫(锥虫)引起的，并通过吸血采采蝇传播。AAT影响牛，以及包括猪、绵羊和山羊在内的一系列其他动物。目前还没有针对AAT的疫苗，迫切需要新药来对抗对当前药物日益增长的耐药性。AAT阻碍了许多非洲国家的发展，因为它对牲畜生产和放牧动物产生有害影响，严重限制了农业生产力，影响了人民的财富、生计和健康。气候变化可能会通过采采蝇分布的变化改变疾病的传播动态来加剧AAT的影响。尽管近年来在消除人类非洲锥虫病或昏睡病方面取得了重大进展，但对导致AAT(相当于牲畜疾病)的寄生虫的研究缺乏动力。几种锥虫引起AAT，宿主范围既包括野生动物，也包括家畜，使其成为一种复杂的疾病，需要与之抗争。在这些锥虫中，有些寄主范围很广，包括牛、小型反刍动物和猪，而另一些则仅限于猪。限制某些牲畜宿主的潜在原因尚不清楚。在这里，我们将通过观察限制猪的锥体如何起源并随着时间的推移与具有更广泛宿主范围的锥体的分化来调查宿主特异性是否具有遗传基础。我们将利用基因测序技术的最新进展，从每个锥虫体内获得完整的基因集-基因组。在布里斯托尔，我们有一个在撒哈拉以南非洲多年的田野工作中分离出来的独特的锥虫集合，我们将用它们来提取纯化的DNA，用于基因组测序。每个基因组都将被仔细组装，使我们能够比较锥体之间单个基因序列和数量的差异。例如，我们将能够确定某些基因或变异是否与猪宿主的适应有关。这不仅允许我们测试有关主机专一性如何演变的假设，而且还可以预测未来主机交换机的概率。我们将获得的新的锥虫基因组序列也将成为未来研究这些重要寄生虫的重要资源，包括药物开发。对AAT的研究通常集中在牛身上，而不是其他牲畜，但猪和小型反刍动物也患有AAT，这些牲畜作为食物和财富的来源对小农来说变得越来越重要。因此，控制AAT对于增加撒哈拉以南非洲的粮食生产和供应，从而推动可持续农业和粮食安全方面的全球发展目标而言，是一项重要任务。

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.