Genomic consequences of schistosome hybridization

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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.