de Groote, Robin

De Muylder, G\ue9raldine

Domagalska, Malgorzata

Dujardin, Jean-Claude

Maes, Ilse

Monsieurs, Pieter

Negreira, Gabriel H.

Van den Broeck, Frederik

Van Giel, Dorien

Abstract: 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

Institutional Repository Universiteit Antwerpen

The adaptive roles of aneuploidy and polyclonality in Leishmania in response to environmental stress

The adaptive roles of aneuploidy and polyclonality in Leishmania in response to environmental stress

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Institutional Repository Universiteit Antwerpen