Genomic consequences of schistosome hybridization

寄生虫物种之间的杂交有可能在物种之间转移重要的生物医学基因 对宿主特异性、致病机制和耐药性有潜在影响的界限。人们普遍认为 家畜寄生虫牛血吸虫和人类寄生虫之间经常进行杂交。 西非的美国血瘤杆菌：这已经成为“一个健康”疾病治疗方法的典范 管理层。这些血吸虫物种之间的遗传杂交可以在实验室进行，并且 多篇论文描述了感染人类的血吸虫和牛链球菌之间的“杂交”血吸虫。 感染牛。然而，这些实地研究的一个中心问题是，单个线粒体和核糖体DNA 标记是用来表征寄生虫幼虫的。在这种有限的基因组分辨率下，目前还不清楚 杂交经常发生，无论是罕见的和古老的，还是从未发生过的杂交 不和谐是由祖先世系分类造成的。我们的初步数据与罕见的古代 杂交和随后的导入，而不是广泛的正在进行的杂交。我们进行了测序 从尼日尔和坦桑尼亚收集的毛虫外显子揭示：(A)没有证据表明最近的杂交，(B) 所有来自尼日尔的嗜血杆菌都在它们的基因组中携带5-8%的牛链球菌DNA(C)导入牛链球菌的大小 片段表明古代杂交(100-600代前)(D)牛链球菌DNA已上升到高水平 血瘤链霉菌基因组的某些区域出现频率，表明适应性渗入。的中心目标是 这个应用是利用基因组测序、种群基因组学和实验分析来理解 血瘤链霉菌与牛链霉菌杂交的频率和基因组后果。我们有 开发了从粪便或蜗牛样本中提取单个寄生虫幼虫的全基因组测序方法：IN 目的1检测395株牛链球菌和血瘤链球菌的基因组序列。 或来自非洲14个国家和尼日利亚10个州的成虫。我们将使用这些数据来 严格评估：(A)最近(F1或F2)杂交的证据，(B)确定有多少次导入 (C)确定富含或缺乏牛链球菌等位基因的基因组区域；以及(D)确定 已经发生渗入的地理区域。在目标2中，我们将进行实验性的遗传杂交 在啮齿类动物中检测牛链球菌和血瘤链球菌之间的关系以确定病毒的基因组和表型后果 杂交。特别是，我们将确定涉及蜗牛穿透毛虫幼虫的基因组区域。 以及皮肤对尾虫的穿透情况，以确定杂交对宿主特异性的影响。最后，在目标3中 我们将检查从西非啮齿动物的自然血吸虫感染中回收的成虫和卵 以确定是否可能发生罕见的杂交事件。结果将解决基本问题和应用问题 关于物种边界、杂交、寄主专一性和生物医学中的导入的问题 重要的和实验上易驯化的寄生虫物种。

Hybridization between parasite species has the potential to transfer biomedically important genes across species boundaries with potential impact on host specificity, pathogenesis and drug resistance. It is widely assumed that there is frequent ongoing hybridization between the livestock parasite Schistosoma bovis and the human parasite S. haematobium in West Africa: this has become a poster child for “one health” approaches to disease management. Genetic crosses between these schistosome species can be conducted in the laboratory, and multiple papers have described “hybrid” schistosomes between S. haematobium infecting humans and S. bovis infecting cattle. However, a central issue with these field studies is that single mitochondrial and ribosomal DNA markers are used to characterize parasite larvae. With this limited genomic resolution it is unclear whether hybridization occurs frequently, whether it is rare and ancient, or if hybridization has never occurred and the discordance results from ancestral lineage sorting. Our preliminary data are consistent with rare ancient hybridization and subsequent introgression, rather than widespread, ongoing hybridization. We sequenced exomes from miracidia collected from Niger and Tanzania revealing (a) no evidence for recent hybrids, (b) that all S. haematobium from Niger carry 5-8% of S. bovis DNA in their genome (c) the size of introgressed S. bovis fragments indicated ancient hybridization (100-600 generations ago) (d) that S. bovis DNA has risen to high frequency some regions of the S. haematobium genome suggesting adaptive introgression. The central goal of this application is to use genome sequencing, population genomics and experimental analyses to understand the frequency and genomic consequences of hybridization between S. haematobium and S. bovis. We have developed methods for whole genome sequencing from single parasite larvae from fecal samples or snails: In Aim 1 we will examine 395 genome sequences of S. bovis and S. haematobium from archived parasite larvae or adult worms from 14 countries from across Africa and from 10 states in Nigeria. We will use these data to critically evaluate: (a) evidence for recent (F1 or F2) hybridization, (b) to determine how many times introgression has occurred; (c) identify genome regions that are enriched or depleted in S. bovis alleles; and (d) to define geographical regions in which introgression has occurred. In Aim 2 we will stage experimental genetic crosses between S. bovis and S. haematobium in rodents to determine genomic and phenotypic consequences of hybridization. In particular, we will determine genome regions involved in snail penetration of miracidia larvae and skin penetration of cercariae to determine the impact of hybridization on host specificity. Finally, in Aim 3 we will examine both adult worms and eggs recovered from natural schistosome infections of West Africa rodents to determine whether rare hybridization events may occur. The results will address fundamental and applied questions concerning species boundaries, hybridization, host specificity and introgression in a biomedically important and experimentally tractable parasite species.