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Abstract

Ongoing elimination efforts have altered the global distribution of Onchocerca volvulus, the agent of river blindness, and further population restructuring is expected as efforts continue. Therefore, a better understanding of population genetic processes and their effect on biogeography is needed to support elimination goals. We describe O. volvulus genome variation in 27 isolates from the early 1990s (before widespread mass treatment) from four distinct locales: Ecuador, Uganda, the West African forest and the West African savanna. We observed genetic substructuring between Ecuador and West Africa and between the West African forest and savanna bioclimes, with evidence of unidirectional gene flow from savanna to forest strains. We identified forest:savanna-discriminatory genomic regions and report a set of ancestry informative loci that can be used to differentiate between forest, savanna and admixed isolates, which has not previously been possible. We observed mito-nuclear discordance possibly stemming from incomplete lineage sorting. The catalogue of the nuclear, mitochondrial and endosymbiont DNA variants generated in this study will support future basic and translational onchocerciasis research, with particular relevance for ongoing control programmes, and boost efforts to characterize drug, vaccine and diagnostic targets.

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  • 14 July 2017

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Acknowledgements

The sequencing work was funded by NIH–NHGRI (U54HG003079) and the genetic variation analysis was funded by NIH–NIAID (R01AI081803) and the Bill & Melinda Gates Foundation (OPP GH 1083853). The study was also funded, in part, by the Division of Intramural Research, National Institute of Allergy and Infectious Diseases. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. The findings and conclusions contained within are those of the authors and do not necessarily reflect positions or policies of the Bill & Melinda Gates Foundation. The authors thank the faculty and staff of the McDonnell Genome Institute who contributed to this study, and thank the physicians and fieldworkers in the endemic countries for their extensive help in collecting the parasite material. The unpublished RNAseq data used in this study were produced by the parasite genomics group at the Wellcome Trust Sanger Institute in collaboration with the laboratories of T. B. Nutman and S. Lustigman.

Author information

Author notes

    • Young-Jun Choi
    •  & Rahul Tyagi

    These authors contributed equally to this work.

Affiliations

  1. McDonnell Genome Institute, Washington University in St Louis, St Louis, Missouri 63108, USA

    • Young-Jun Choi
    • , Rahul Tyagi
    • , Samantha N. McNulty
    • , Bruce A. Rosa
    • , Philip Ozersky
    • , John Martin
    • , Kymberlie Hallsworth-Pepin
    •  & Makedonka Mitreva
  2. Global Health Infectious Disease Research Program, Department of Global Health, University of South Florida, Tampa, Florida 33612, USA

    • Thomas R. Unnasch
  3. Laboratory of Parasitic Diseases, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland 20892, USA

    • Carmelle T. Norice
    •  & Thomas B. Nutman
  4. Division of Infectious Diseases, Department of Medicine, Washington University School of Medicine, St Louis, Missouri 63110, USA

    • Gary J. Weil
    • , Peter U. Fischer
    •  & Makedonka Mitreva

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Contributions

Y.-J.C. and R.T. contributed equally to this work. M.M., P.U.F. and G.J.W. conceived and planned the project. M.M. led the project, and carried out analysis and manuscript preparation. T.R.U., C.T.N., T.B.N. and P.U.F. provided material. K.H.-P., P.O. and J.M. carried out sequence data production, annotation and submission. Y.C., R.T., B.A.R. and S.M.N.M performed genome-based variant studies. M.M., R.T., Y.C., S.N.M. and B.A.R. drafted, edited and wrote the manuscript.

Competing interests

The authors declare no competing financial interest.

Corresponding author

Correspondence to Makedonka Mitreva.

Supplementary information

PDF files

  1. 1.

    Supplementary Information

    Legends for Supplementary Tables 1-9, Supplementary Figures 1-10

Excel files

  1. 1.

    Supplementary Table 1

    Classifications, sources and read mapping data for each of the samples utilized

  2. 2.

    Supplementary Table 2

    SnpEff annotations and allele frequency data per SNP position

  3. 3.

    Supplementary Table 3

    Summary of results from the FST sliding window analysis

  4. 4.

    Supplementary Table 4

    FST genome scan sliding window positions, summary statistics, and overlapping genes

  5. 5.

    Supplementary Table 5

    Detailed functional annotation and SNP annotation per gene

  6. 6.

    Supplementary Table 6

    ABBA-BABA analysis results for gene flow

  7. 7.

    Supplementary Table 7

    Ancestry Informative Markers for distinguishing savanna from forest O. volvulus isolates

  8. 8.

    Supplementary Table 8

    Variants ranked by FST (FOR:SAV comparison, minimum value 0.5)

  9. 9.

    Supplementary Table 9

    Sources, dates, and processing procedures for each of the whole genome shotgun libraries in each of the samples

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https://doi.org/10.1038/nmicrobiol.2016.207