1. High throughput single-cell genome sequencing gives insights into the generation and evolution of mosaic aneuploidy in Leishmania donovani
- Author
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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, Institute of Tropical Medicine [Antwerp] (ITM), Maladies infectieuses et vecteurs : écologie, génétique, évolution et contrôle (MIVEGEC), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD [France-Sud])-Université de Montpellier (UM), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), Laboratoire de parasitologie-mycologie, CHU Grenoble, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), University of Antwerp (UA), Flemish Ministry of Science and Innovation [Secondary Research Funding ITM – SOFI, Grant MADLEI], FlemishFund for Scientific Research [FWO, post-doctoral grantto F.V.dB.], Agence Nationale de la Recherche (ANR)(to A.Y. within the frame of the ‘Investissements d’avenir’programme [ANR 11-LABX-0024-01, ‘ParaFrap’]). Funding for open access charge: Department of Economy, Science and Innovation, Flanders (Secondary Research Funding ITM - SOFI), and ANR-11-LABX-0024,ParaFrap,Alliance française contre les maladies parasitaires(2011)
- Subjects
Biochemistry & Molecular Biology ,[SDV.GEN]Life Sciences [q-bio]/Genetics ,Science & Technology ,Whole Genome Sequencing ,Mosaicism ,STRAINS ,[SDV]Life Sciences [q-bio] ,GENETIC EXCHANGE ,Aneuploidy ,READ ALIGNMENT ,MECHANISMS ,Evolution, Molecular ,Chemistry ,Genetics ,YEAST ,R PACKAGE ,Single-Cell Analysis ,Biology ,Genome, Protozoan ,Life Sciences & Biomedicine ,RESISTANCE ,Leishmania donovani - 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. ispartof: NUCLEIC ACIDS RESEARCH vol:50 issue:1 pages:293-305 ispartof: location:England status: published
- Published
- 2022