TY - JOUR
T1 - The adaptive roles of aneuploidy and polyclonality in Leishmania in response to environmental stress
AU - Negreira, Gabriel H
AU - de Groote, Robin
AU - Van Giel, Dorien
AU - Monsieurs, Pieter
AU - Maes, Ilse
AU - de Muylder, Geraldine
AU - Van den Broeck, Frederik
AU - Dujardin, Jean-Claude
AU - Domagalska, Malgorzata A
N1 - FTX; (CC BY-NC-ND 4.0); © 2023 The Authors. Published under the terms of the CC BY NC ND 4.0 license.
PY - 2023
Y1 - 2023
N2 - Aneuploidy is generally considered harmful, but in some microorganisms, it can act as an adaptive mechanism against environmental stress. Here, we use Leishmania-a protozoan parasite with remarkable genome plasticity-to study the early steps of aneuploidy evolution under high drug pressure (using antimony or miltefosine as stressors). By combining single-cell genomics, lineage tracing with cellular barcodes, and longitudinal genome characterization, we reveal that aneuploidy changes under antimony pressure result from polyclonal selection of pre-existing karyotypes, complemented by further and rapid de novo alterations in chromosome copy number along evolution. In the case of miltefosine, early parasite adaptation is associated with independent point mutations in a miltefosine transporter gene, while aneuploidy changes only emerge later, upon exposure to increased drug levels. Therefore, polyclonality and genome plasticity are hallmarks of parasite adaptation, but the scenario of aneuploidy dynamics depends on the nature and strength of the environmental stress as well as on the existence of other pre-adaptive mechanisms.
AB - Aneuploidy is generally considered harmful, but in some microorganisms, it can act as an adaptive mechanism against environmental stress. Here, we use Leishmania-a protozoan parasite with remarkable genome plasticity-to study the early steps of aneuploidy evolution under high drug pressure (using antimony or miltefosine as stressors). By combining single-cell genomics, lineage tracing with cellular barcodes, and longitudinal genome characterization, we reveal that aneuploidy changes under antimony pressure result from polyclonal selection of pre-existing karyotypes, complemented by further and rapid de novo alterations in chromosome copy number along evolution. In the case of miltefosine, early parasite adaptation is associated with independent point mutations in a miltefosine transporter gene, while aneuploidy changes only emerge later, upon exposure to increased drug levels. Therefore, polyclonality and genome plasticity are hallmarks of parasite adaptation, but the scenario of aneuploidy dynamics depends on the nature and strength of the environmental stress as well as on the existence of other pre-adaptive mechanisms.
KW - Aneuploidy
KW - Antimony
KW - Chromosomes
KW - Humans
KW - Leishmania/genetics
U2 - 10.15252/embr.202357413
DO - 10.15252/embr.202357413
M3 - A1: Web of Science-article
C2 - 37470283
SN - 1469-221X
VL - 24
JO - Embo Reports
JF - Embo Reports
IS - 9
M1 - e57413
ER -