Modulation of aneuploidy in leishmania donovani during adaptation to different in vitro and in vivo environments and its impact on gene expression

Dumetz, F. 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. (doi: 10.1128/mBio.00599-17) (PMID:28536289) (PMCID:PMC5442457)

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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.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Cotton, Professor James and Berriman, Professor Matt
Authors: Dumetz, F., Imamura, H., Sanders, M., Seblova, V., Myskova, J., Pescher, P., Vanaerschot, M., Meehan, C.J., Cuypers, B., De Muylder, G., Späth, G.F., Bussotti, G., Vermeesch, J.R., Berriman, M., Cotton, J.A., Volf, P., Dujardin, J.C., and Domagalska, M.A.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:mBio
Publisher:American Society for Microbiology
ISSN (Online):2150-7511
Published Online:23 May 2017
Copyright Holders:Copyright © 2017 Dumetz et al.
First Published:First published in mBio 8(3): e00599-17
Publisher Policy:Reproduced under a Creative Commons License

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