TY - JOUR
T1 - High throughput single-cell genome sequencing gives insights into the generation and evolution of mosaic aneuploidy in Leishmania donovani
AU - Negreira, Gabriel H
AU - Monsieurs, Pieter
AU - Imamura, Hideo
AU - Maes, Ilse
AU - Kuk, Nada
AU - Yagoubat, Akila
AU - Van den Broeck, Frederik
AU - Sterkers, Yvon
AU - Dujardin, Jean-Claude
AU - Domagalska, Malgorzata A
N1 - FTX; (CC BY 4.0); © The Author(s) 2021. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - Aneuploidy
KW - Evolution, Molecular
KW - Genome, Protozoan
KW - Leishmania donovani/genetics
KW - Mosaicism
KW - Single-Cell Analysis/methods
KW - Whole Genome Sequencing/methods
UR - https://www.webofscience.com/api/gateway?GWVersion=2&SrcApp=itm_wosliteitg&SrcAuth=WosAPI&KeyUT=WOS:000749588900025&DestLinkType=FullRecord&DestApp=WOS_CPL
U2 - 10.1093/nar/gkab1203
DO - 10.1093/nar/gkab1203
M3 - A1: Web of Science-article
C2 - 34893872
SN - 0305-1048
VL - 50
SP - 293
EP - 305
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 1
ER -