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生物医学上重要的基因 对宿主特异性、发病机制和耐药性有潜在影响的边界。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 S.西非的埃及伊蚊：这已成为“一种健康”方法治疗疾病的典范 管理在实验室中可以进行这些杂交物种之间的遗传杂交， 多篇论文描述了S.感染人类的埃及血吸虫和S.牛 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 标记物用于表征寄生虫幼虫。由于这种有限的基因组分辨率，尚不清楚是否 杂交经常发生，无论它是罕见的和古老的，或者如果杂交从未发生过， 不一致性是由祖先血统分类造成的。我们的初步数据与罕见的 杂交和随后的渐渗，而不是广泛的，正在进行的杂交。我们测序 从尼日尔和坦桑尼亚收集的毛蚴的外显子组揭示（a）没有最近杂交的证据，（B） 所有鼠伤寒沙门产自尼日尔埃及血吸虫携带5-8%的S.牛的DNA在它们的基因组中（c）渗入的S.牛 片段显示了古老的杂交（100-600代前）。牛的DNA含量已经上升到 频率的一些地区的S。haematobium基因组表明适应性渐渗。的中心目标 这个应用程序是使用基因组测序，人口基因组学和实验分析， S. haematobium和S.牛我们有 从粪便样本或蜗牛中的单个寄生虫幼虫开发的全基因组测序方法： 目的1.对395株S. bovis和S.来自存档寄生虫幼虫的血吸虫 或者来自非洲14个国家和尼日利亚10个州的蠕虫。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）确定有多少次基因渗入 （c）鉴定富集或耗尽S.牛等位基因;和（d）定义 发生基因渗入的地理区域。在目标2中，我们将进行实验性遗传杂交 在S。bovis和S.在啮齿类动物中的嗜血杆菌，以确定基因组和表型后果 杂交方法特别是，我们将确定毛蚴幼虫的蜗牛渗透所涉及的基因组区域 和尾蚴的皮肤穿透，以确定杂交对宿主特异性的影响。最后，在Aim 3中 我们将检查从西非啮齿动物的自然寄生虫感染中回收的蠕虫和虫卵， 以确定是否可能发生罕见的杂交事件。结果将解决基本和应用 生物医学领域中有关物种边界、杂交、宿主特异性和渐渗的问题 重要的和实验上易处理的寄生虫种类。

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.