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    Modulation of Aneuploidy in Leishmania donovani during Adaptation to Different In Vitro and In Vivo Environments and Its Impact on Gene Expression.

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    Publication date
    2017-05
    Author
    Dumetz, F.
    Imamura, H.
    Sanders, M.
    Seblova, V.
    Myskova, J.
    Pescher, P.
    Vanaerschot, M.
    Meehan, Conor J.
    Cuypers, B.
    De Muylder, G.
    Späth, G.F.
    Bussotti, G.
    Vermeesch, J.R.
    Berriman, M.
    Cotton, J.A.
    Volf, P.
    Dujardin, J.-C.
    Domagalska, M.A.
    Show allShow less
    Keyword
    Leishmania
    Aneuploidy
    Gene dosage
    Genomics
    Life cycle
    Rights
    © 2017 Dumetz et al. This is an open-access article distributed under the terms of the Creative Commons Attribution 4.0 International license.
    Peer-Reviewed
    Yes
    
    Metadata
    Show full item record
    Abstract
    Aneuploidy is usually deleterious in multicellular organisms but appears to be tolerated and potentially beneficial in unicellular organisms, including pathogens. Leishmania, a major protozoan parasite, is emerging as a new model for aneuploidy, since in vitro-cultivated strains are highly aneuploid, with interstrain diversity and intrastrain mosaicism. The alternation of two life stages in different environments (extracellular promastigotes and intracellular amastigotes) offers a unique opportunity to study the impact of environment on aneuploidy and gene expression. We sequenced the whole genomes and transcriptomes of Leishmania donovani strains throughout their adaptation to in vivo conditions mimicking natural vertebrate and invertebrate host environments. The nucleotide sequences were almost unchanged within a strain, in contrast to highly variable aneuploidy. Although high in promastigotes in vitro, aneuploidy dropped significantly in hamster amastigotes, in a progressive and strain-specific manner, accompanied by the emergence of new polysomies. After a passage through a sand fly, smaller yet consistent karyotype changes were detected. Changes in chromosome copy numbers were correlated with the corresponding transcript levels, but additional aneuploidy-independent regulation of gene expression was observed. This affected stage-specific gene expression, downregulation of the entire chromosome 31, and upregulation of gene arrays on chromosomes 5 and 8. Aneuploidy changes in Leishmania are probably adaptive and exploited to modulate the dosage and expression of specific genes; they are well tolerated, but additional mechanisms may exist to regulate the transcript levels of other genes located on aneuploid chromosomes. Our model should allow studies of the impact of aneuploidy on molecular adaptations and cellular fitness.
    URI
    http://hdl.handle.net/10454/17310
    Version
    Published version
    Citation
    Dumetz F, Imamura H, Sanders M et al (2017) Modulation of Aneuploidy in Leishmania donovani during Adaptation to Different In Vitro and In Vivo Environments and Its Impact on Gene Expression. mBio, 8 (3): e00599-17.
    Link to publisher’s version
    https://doi.org/10.1128/mBio.00599-17
    Type
    Article
    Collections
    Life Sciences Publications

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