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Nucleic Acids Res. 2022 Jan 11;50(1):293-305. doi: 10.1093/nar/gkab1203.

High throughput single-cell genome sequencing gives insights into the generation and evolution of mosaic aneuploidy in Leishmania donovani.

Nucleic acids research

Gabriel H Negreira, Pieter Monsieurs, Hideo Imamura, Ilse Maes, Nada Kuk, Akila Yagoubat, Frederik Van den Broeck, Yvon Sterkers, Jean-Claude Dujardin, Malgorzata A Domagalska

Affiliations

  1. Molecular Parasitology Unit, Institute of Tropical Medicine, Antwerp, Belgium.
  2. MiVEGEC, University of Montpellier, CNRS, IRD, Montpellier, France.
  3. Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, Katholieke Universiteit Leuven, 3000 Leuven, Belgium.
  4. Department of Biomedical Sciences, University of Antwerp, Belgium.

PMID: 34893872 DOI: 10.1093/nar/gkab1203

Abstract

Leishmania, a unicellular eukaryotic parasite, is a unique model for aneuploidy and cellular heterogeneity, along with their potential role in adaptation to environmental stresses. Somy variation within clonal populations was previously explored in a small subset of chromosomes using fluorescence hybridization methods. This phenomenon, termed mosaic aneuploidy (MA), might have important evolutionary and functional implications but remains under-explored due to technological limitations. Here, we applied and validated a high throughput single-cell genome sequencing method to study for the first time the extent and dynamics of whole karyotype heterogeneity in two clonal populations of Leishmania promastigotes representing different stages of MA evolution in vitro. We found that drastic changes in karyotypes quickly emerge in a population stemming from an almost euploid founder cell. This possibly involves polyploidization/hybridization at an early stage of population expansion, followed by assorted ploidy reduction. During further stages of expansion, MA increases by moderate and gradual karyotypic alterations, affecting a defined subset of chromosomes. Our data provide the first complete characterization of MA in Leishmania and pave the way for further functional studies.

© The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.

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