The parasite Leishmania  donovani causes a fatal disease termed visceral leishmaniasis. The process through which the parasite adapts to environmental change remains largely unknown. Here we show that aneuploidy is integral for parasite adaptation and that karyotypic fluctuations allow for selection of beneficial haplotypes, which impact transcriptomic output and correlate with phenotypic variations in proliferation and infectivity. To avoid loss of diversity following karyotype and haplotype selection, L. donovani utilizes two mechanisms: polyclonal selection of beneficial haplotypes to create coexisting subpopulations that preserve the original diversity, and generation of new diversity as aneuploidy-prone chromosomes tolerate higher mutation rates. Our results reveal high aneuploidy turnover and haplotype selection as a unique evolutionary adaptation mechanism that L. donovani uses to preserve genetic diversity under strong selection. This unexplored process may function in other human diseases, including fungal infection and cancer, and stimulate innovative treatment options.

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Work on samples from the Indian subcontinent was supported by the European Union 7th Framework Programme (EU FP7) (Kaladrug-R, contract 222895), the Belgian Science Policy Office (TRIT, P7/41), the Department of Economy, Science and Innovation in Flanders (ITM-SOFIB) and the Flemish Fund for Scientific Research (G.0.B81.12). We thank Life Science Editors for editing assistance. This study recieved funding from Plan Nacional (BFU2011-28575 to C.N., P.P.B. and D.K.), Center for Genomic Regulation (CRG), Spanish Ministry of Economy and Competitiveness, ‘Centro de Excelencia Severo Ochoa 2013–2017’ (SEV-2012–0208), a grant from the Institut Pasteur International Department strategic fund to the LeiSHield consortium (P.P.B., P.P, C.N., G.F.S., G.B. and Y.S.), Agence Nationale de la Recherche (ANR) within the framework of the 'Investissements d’avenir' programme (ANR-11-LABX-0024-01 “PARAFRAP”) (V.C., M.P. and Y.S.), the EU FP7 (Kaladrug-R, contract 222895), the Belgian Science Policy Office (TRIT, P7/41), the Department of Economy, Science and Innovation in Flanders (ITM-SOFIB) and the Flemish Fund for Scientific Research (G.0.B81.12) (J.C.D., F.D., H.I. and M.D.).

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Author notes

  1. These authors contributed equally to this work: Pablo Prieto Barja, Pascale Pescher.


  1. Centre for Genomic Regulation (CRG), The Barcelona Institute of Science and Technology, 08002, Barcelona, Spain

    • Pablo Prieto Barja
    • , Darek Kedra
    • , Heinz Himmelbauer
    •  & Cedric Notredame
  2. Universitat Pompeu Fabra (UPF), 08002, Barcelona, Spain

    • Pablo Prieto Barja
    •  & Cedric Notredame
  3. Institut Pasteur, INSERM U1201, Unité de Parasitologie Moléculaire et Signalisation, 75015, Paris, France

    • Pascale Pescher
    •  & Gerald Frank Späth
  4. HUB de Bioinformatique et Biostatistiques, Centre de Bioinformatique, Biostatistique et Biologie Intégrative (C3BI), Institut Pasteur, 75015, Paris, France

    • Giovanni Bussotti
  5. Institute of Tropical Medicine, Molecular Parasitology Unit, B-2000, Antwerp, Belgium

    • Franck Dumetz
    • , Hideo Imamura
    • , Malgorzata Domagalska
    •  & Jean-Claude Dujardin
  6. University Montpellier, Faculty of Medicine, Laboratory of Parasitology–Mycology, CNRS 5290, IRD 224, University Montpellier (UMR ‘MiVEGEC’) and Centre Hospitalier Universitaire, 34295, Montpellier cedex 5, France

    • Victor Chaumeau
    • , Michel Pages
    •  & Yvon Sterkers
  7. Institute of Biotechnology, 1190, Vienna, Austria

    • Heinz Himmelbauer
  8. Department of Biomedical Sciences, University of Antwerp, B-2610, Antwerp, Belgium

    • Jean-Claude Dujardin


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P.P.B., P.P, C.N. and G.F.S worked on all aspects of work, contributed to the design of the project and wrote the article. G.B contributed to in silico analysis. F.D. and M.D. managed the hamster infection experiment with field isolates. H.I., M.D. and J.-C.D. contributed to the field isolates analyses and revised the paper. D.K. helped analyse the sequencing data. H.H. was responsible for the genomic sequencing of the in vitro clones. V.C., M.P. and Y.S. contributed the DNA-FISH analysis.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Cedric Notredame or Gerald Frank Späth.

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