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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.
Dumetz, F. Imamura, H. Sanders, M. Seblova, V. Myskova, J. Pescher, P. Vanaerschot, M. Meehan, Conor J. Cuypers, B. De Muylder, G.
Dumetz, F.
Imamura, H.
Sanders, M.
Seblova, V.
Myskova, J.
Pescher, P.
Vanaerschot, M.
Meehan, Conor J.
Cuypers, B.
De Muylder, G.
Publication Date
2017-05
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© 2017 Dumetz et al. This is an
open-access article distributed under the terms
of the Creative Commons Attribution 4.0
International license.
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openAccess
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2017-05-01
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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.
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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.
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Article