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.
-
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.
Metrics
-
- 2,200
- views
-
- 256
- downloads
-
- 21
- citations
Views, downloads and citations are aggregated across all versions of this paper published by eLife.
Download links
A two-part list of links to download the article, or parts of the article, in various formats.
Downloads (link to download the article as PDF)
Open citations (links to open the citations from this article in various online reference manager services)
Cite this article (links to download the citations from this article in formats compatible with various reference manager tools)
Clusters of polymorphic transmembrane genes control resistance to schistosomes in snail vectors
eLife 9:e59395.
https://doi.org/10.7554/eLife.59395
Further reading
-
- Epidemiology and Global Health
Background: The role of circulating metabolites on child development is understudied. We investigated associations between children's serum metabolome and early childhood development (ECD).
Methods: Untargeted metabolomics was performed on serum samples of 5,004 children aged 6-59 months, a subset of participants from the Brazilian National Survey on Child Nutrition (ENANI-2019). ECD was assessed using the Survey of Well-being of Young Children's milestones questionnaire. The graded response model was used to estimate developmental age. Developmental quotient (DQ) was calculated as the developmental age divided by chronological age. Partial least square regression selected metabolites with a variable importance projection ≥ 1. The interaction between significant metabolites and the child's age was tested.
Results: Twenty-eight top-ranked metabolites were included in linear regression models adjusted for the child's nutritional status, diet quality, and infant age. Cresol sulfate (β = -0.07; adjusted-p < 0.001), hippuric acid (β = -0.06; adjusted-p < 0.001), phenylacetylglutamine (β = -0.06; adjusted-p < 0.001), and trimethylamine-N-oxide (β = -0.05; adjusted-p = 0.002) showed inverse associations with DQ. We observed opposite directions in the association of DQ for creatinine (for children aged -1 SD: β = -0.05; p =0.01; +1 SD: β = 0.05; p =0.02) and methylhistidine (-1 SD: β = - 0.04; p =0.04; +1 SD: β = 0.04; p =0.03).
Conclusion: Serum biomarkers, including dietary and microbial-derived metabolites involved in the gut-brain axis, may potentially be used to track children at risk for developmental delays.
Funding: Supported by the Brazilian Ministry of Health and the Brazilian National Research Council.
-
- Epidemiology and Global Health
Given the rapid cross-country spread of SARS-CoV-2 and the resulting difficulty in tracking lineage spread, we investigated the potential of combining mobile service data and fine-granular metadata (such as postal codes and genomic data) to advance integrated genomic surveillance of the pandemic in the federal state of Thuringia, Germany. We sequenced over 6500 SARS-CoV-2 Alpha genomes (B.1.1.7) across 7 months within Thuringia while collecting patients’ isolation dates and postal codes. Our dataset is complemented by over 66,000 publicly available German Alpha genomes and mobile service data for Thuringia. We identified the existence and spread of nine persistent mutation variants within the Alpha lineage, seven of which formed separate phylogenetic clusters with different spreading patterns in Thuringia. The remaining two are subclusters. Mobile service data can indicate these clusters’ spread and highlight a potential sampling bias, especially of low-prevalence variants. Thereby, mobile service data can be used either retrospectively to assess surveillance coverage and efficiency from already collected data or to actively guide part of a surveillance sampling process to districts where these variants are expected to emerge. The latter concept was successfully implemented as a proof-of-concept for a mobility-guided sampling strategy in response to the surveillance of Omicron sublineage BQ.1.1. The combination of mobile service data and SARS-CoV-2 surveillance by genome sequencing is a valuable tool for more targeted and responsive surveillance.
