Genomic consequences of schistosome hybridization

血吸虫杂交的基因组后果

• 批准号: 10346459
• 负责人: Tim J Anderson
• 金额: $ 61.37万
• 依托单位: TEXAS BIOMEDICAL RESEARCH INSTITUTE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-09-27 至 2026-08-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10346459
• 关键词: Address; Adult; Africa; African; Alleles; Archives; Biological Assay; Blood; Bulinus; Cattle; Child; Collection; Country; DNA; DNA Markers; Data; Disease Management; Drug resistance; Event; Experimental Genetics; Frequencies; Gene Frequency; Gene Transfer; Generations; Genes; Genetic; Genetic Crosses; Genetic Recombination; Genome; Genomics; Genotype; Geographic Locations; Goals; Hamsters; Hand; Health; Human; Hybrid-B; Hybrids; Individual; Infection; Laboratories; Larva; Liver; Livestock; Medical; Methods; Mitochondrial DNA; Nature; Niger; Nigeria; Nuclear; Paper; Parasites; Parents; Pathogenesis; Pattern; Penetration; Phenotype; Play; Population; Prevalence; Publishing; Reporting; Research; Resolution; Resources; Ribosomal DNA; Rodent; Role; Sampling; Schistosoma; Schistosoma mansoni; Skin; Snails; Sorting - Cell Movement; Specificity; Tanzania; Time; Work; egg; exome; experimental analysis; field study; fitness; genetic linkage analysis; genome sequencing; genome-wide; improved; infected vector rodent; posters; segregation; trait; whole genome

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.

寄生虫物种之间的杂交有可能在物种上转移生物医学重要的基因 边界对宿主特异性，发病机理和耐药性有潜在影响。广泛认为 牲畜寄生虫血吸虫与人类寄生虫之间经常发生杂交 西非的S. haematobium：这已成为“一种健康”疾病方法的海报孩子 管理。这些黑素物种之间的遗传杂交可以在实验室进行，并且 多篇论文描述了葡萄球菌感染人类和牛链球菌之间的“混合”血块 感染牛。但是，这些现场研究的一个核心问题是单线粒体和核糖体DNA 标记用于表征寄生虫幼虫。通过这种有限的基因组分辨率，尚不清楚是否存在 杂交经常发生，无论它是罕见和古老的，还是从未发生过杂交， 不一致是由祖先的谱系分类引起的。我们的初步数据与罕见的古代一致 杂交和随后的渗入，而不是宽度，持续的杂交。我们测序了 从尼日尔和坦桑尼亚收集的奇迹的外体揭示了（a）没有证据表明最近的杂种，（b） 来自尼日尔的所有嗜血杆菌在其基因组中含有5-8％的牛链霉菌DNA（c）浸入的牛S. bovis的大小 片段表明古代杂交（100-600代）（d），S。bovis DNA已上升到高 频率的止血链球菌基因组的某些区域表明自适应渗入。中心目标 该应用是使用基因组测序，种群基因组学和实验分析来了解 造血链球菌和牛链球菌之间杂交的频率和基因组后果。我们有 从粪便样品或蜗牛的单个寄生虫幼虫中进行整个基因组测序的开发方法： AIM 1我们将检查来自存档寄生虫幼虫的395个基因组和嗜血杆菌的基因组序列 或来自非洲各地和尼日利亚10个州的14个国家的成年蠕虫。我们将使用这些数据来 批判性评估：（a）最近（F1或F2）杂交的证据，（b）确定渗入多少次 发生了； （c）鉴定在牛链球菌等位基因中富集或耗尽的基因组区域； （d）定义 发生渗入的地理区域。在AIM 2中，我们将进行实验性遗传杂交 在啮齿动物中的牛链球菌和止血链球菌之间，以确定基因组和表型后果 杂交。特别是，我们将确定幼虫的蜗牛渗透涉及的基因组区域 尾骨的皮肤穿透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天然黑素感染中回收的成年蠕虫和卵 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 关于物种边界，杂交，宿主特异性和渗入的问题 重要且具有实验性的寄生虫物种。