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

非洲锥虫宿主特异性的遗传基础：为什么有些物种更喜欢猪？

• 批准号: BB/R016437/1
• 负责人: Wendy Gibson
• 金额: $ 32.32万
• 依托单位: University of Bristol
• 依托单位国家: 英国
• 项目类别: Research Grant
• 财政年份: 2018
• 资助国家: 英国
• 起止时间: 2018 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=BB%2FR016437%2F1
• 关键词: genetic; basis; host; specificity; African

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.

动物非洲锥虫病（AAT）是一种对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产生影响。这种疾病是由感染动物血液中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，以及一系列其他动物，包括猪，绵羊和山羊。目前还没有针对AAT的疫苗，迫切需要新的药物来对抗对当前药物日益增加的耐药性。农业可持续发展阻碍了许多非洲国家的发展，因为它对畜牧业生产和耕畜产生有害影响，严重制约了农业生产力，影响到人民的财富、生计和健康。气候变化可能会通过改变采采蝇分布改变疾病的传播动力来加剧AAT的影响。虽然近年来一直在大力推动消除人类非洲锥虫病或昏睡病，但对导致AAT（相当于牲畜疾病）的寄生虫的研究缺乏动力。几种锥虫物种引起AAT，宿主范围包括野生动物和家畜，使其成为一种复杂的疾病。在这些锥虫中，一些具有广泛的宿主范围，包括牛、小型反刍动物和猪，而另一些仅限于猪。限制某些牲畜宿主的根本原因尚不清楚。在这里，我们将研究宿主特异性是否具有遗传基础，通过观察猪限制性锥虫如何起源并随着时间的推移从具有更广泛宿主范围的锥虫中分化出来。我们将利用基因测序技术的最新进展，从每一个锥虫获得完整的基因组。在布里斯托，我们有一个独特的锥虫收集多年来在撒哈拉以南非洲地区的实地工作中分离出来，我们将使用它来提取纯化的DNA进行基因组测序。每个基因组将被仔细组装，使我们能够比较锥虫之间单个基因的序列和数量的变化。例如，我们将能够确定某些基因或变异是否与适应猪宿主有关。这不仅使我们能够测试宿主特异性如何进化的假设，而且还可以预测未来宿主转换的概率。我们将获得的新锥虫基因组序列也将成为未来研究这些重要寄生虫（包括药物开发）的重要资源。对反式乙酰氨基酚的研究往往集中在牛身上，而不包括其他牲畜，但猪和小型反刍动物也患有反式乙酰氨基酚，这些牲畜作为小农的食物和财富来源越来越重要。因此，控制农业可持续发展是增加撒哈拉以南非洲粮食生产和供应的一项重要任务，从而推动实现可持续农业和粮食安全方面的全球发展目标。

项目成果

Additional file 4 of Mitochondrial DNAs provide insight into trypanosome phylogeny and molecular evolution

线粒体 DNA 的附加文件 4 提供了对锥虫系统发育和分子进化的深入了解

• DOI: 10.6084/m9.figshare.13357203
• 发表时间: 2020
• 作者: C. Kay

Additional file 7 of Mitochondrial DNAs provide insight into trypanosome phylogeny and molecular evolution

线粒体 DNA 的附加文件 7 提供了对锥虫系统发育和分子进化的深入了解

• DOI: 10.6084/m9.figshare.13357212
• 发表时间: 2020
• 作者: C. Kay

Additional file 9 of Mitochondrial DNAs provide insight into trypanosome phylogeny and molecular evolution

线粒体 DNA 的附加文件 9 提供了对锥虫系统发育和分子进化的深入了解

• DOI: 10.6084/m9.figshare.13357218
• 发表时间: 2020
• 作者: C. Kay

Additional file 3 of Mitochondrial DNAs provide insight into trypanosome phylogeny and molecular evolution

线粒体 DNA 的附加文件 3 提供了对锥虫系统发育和分子进化的深入了解

• DOI: 10.6084/m9.figshare.13357200
• 发表时间: 2020
• 作者: C. Kay

Additional file 8 of Mitochondrial DNAs provide insight into trypanosome phylogeny and molecular evolution

线粒体 DNA 的附加文件 8 提供了对锥虫系统发育和分子进化的深入了解

• DOI: 10.6084/m9.figshare.13357215
• 发表时间: 2020
• 作者: C. Kay