Genomic consequences of schistosome hybridization

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.

Grant Number: 5R01AI166049-05
NIH Institute/Center: NIH
Principal Investigator: Tim Anderson