Yes / 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. / This study was supported by Belgian Science Policy Office (TRIT, P7/41), Flemish Fund for Scientific Research (G.0.B81.12), and Department of Economy, Science and Innovation in Flanders ITM-SOFIB (SINGLE project, to J.C.D.). G.D. and B.C. were supported by the Research Foundation—Flanders (FWO) (grants 12Q8115N and 11O1614N, respectively). V.S., J.M. and P.V. were supported by Czech Science Foundation (project no. 13-07500S) and Charles University (UNCE 204017/2012). J.R.V. was supported by research grants from the KU Leuven (SymBioSys [PFV/10/016]) and the Hercules Foundation (ZW11-14). M.S., M.B., and J.A.C. were supported by the Wellcome Trust through the core support for the Wellcome Trust Sanger Institute (grant no. 098051). G.B., P.P., and G.F.S. were supported by Institut Pasteur strategic fund for the LeiSHield project (to G.F.S.).
| Identifer | oai:union.ndltd.org:BRADFORD/oai:bradscholars.brad.ac.uk:10454/17310 |
| Date | 24 September 2019 |
| Creators | 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. |
| Source Sets | Bradford Scholars |
| Language | English |
| Detected Language | English |
| Type | Article, Published version |
| Rights | © 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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