Clusters of polymorphic transmembrane genes control resistance to schistosomes in snail vectors
- Harvard T.H. Chan School of Public Health, United States
- Oregon State University, United States
Abstract
Schistosomiasis is a debilitating parasitic disease infecting hundreds of millions of people. Schistosomes use aquatic snails as intermediate hosts. A promising avenue for disease control involves leveraging innate host mechanisms to reduce snail vectorial capacity. In a genome-wide association study of Biomphalaria glabrata snails, we identify genomic region PTC2 which exhibits the largest known correlation with susceptibility to parasite infection (>15-fold effect). Using new genome assemblies with substantially higher contiguity than the Biomphalaria reference genome, we show that PTC2 haplotypes are exceptionally divergent in structure and sequence. This variation includes multi-kilobase indels containing entire genes, and orthologs for which most amino acid residues are polymorphic. RNA-Seq annotation reveals that most of these genes encode single-pass transmembrane proteins, as seen in another resistance region in the same species. Such groups of hyperdiverse snail proteins may mediate host-parasite interaction at the cell surface, offering promising targets for blocking the transmission of schistosomiasis.
Data availability
All data not included in the manuscript are available at NCBI. PacBio genome assemblies are available under BioProject Accession PRJNA639204. Pooled whole-genome sequencing reads are available under BioProject Accession PRJNA638474. RNA-Seq reads are available under BioProject Accession PRJNA639026. Assembled transcripts are on Genbank, Accessions MT787302-MT787323.
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Biomphalaria glabrata genome BglaB1VectorBase Biomphalaria glabrata.
Article and author information
Author details
Michael Scott Blouin
Funding
National Institutes of Health (AI143991)
- Professor Michael Scott Blouin
The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.
Ethics
Animal experimentation: We used mice to maintain the schistosome parasites and to produce miracidia for challenge experiments. Infection is through contact with inoculated water and involves minimal discomfort. Infected rodents are euthanized with CO2 prior to showing clinical signs of disease and are dissected to recover parasitic eggs. Animal numbers were held to the minimum required for the research. Institutional approval: Oregon State University Animal Care and Use Protocols 4749 and 5115.
Copyright
© 2020, Tennessen et al.
This article is distributed under the terms of the Creative Commons Attribution License permitting unrestricted use and redistribution provided that the original author and source are credited.
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Clusters of polymorphic transmembrane genes control resistance to schistosomes in snail vectors
eLife 9:e59395.
https://doi.org/10.7554/eLife.59395
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