Revealing the molecular mechanisms and adaptive role of aneuploidy plasticity in Leishmania spp

Most eukaryotes have evolved to maintain strict control over the structural transmission of their genomes across several generations. However, in Leishmania, this is not the case. These protozoan parasites have a highly plastic genome characterized by rapid modulation of chromosome copy number, leading to the co-existence of cells with diverging aneuploid karyotypes even in clonal populations. Such modulations in aneuploidy are reflected on both transcriptome and proteome, creating a range of phenotypes that can serve as substrate for selection against different environment stresses. However, the potential adaptive role of aneuploidy heterogeneity remains underexplored especially in the context of natural environments faced by Leishmania throughout its life cycle. Moreover, the molecular mechanisms that govern the generation of new aneuploidy

modifications – referred here as aneuploidy plasticity – are currently unknown. Preliminary data suggests that aneuploidy plasticity increases during adaptation to in vitro culture, indicating that potential for aneuploidy modulations is dynamic and might be regulated as a response to environmental stresses. In this proposal, we aim to reveal the molecular mechanisms that control aneuploidy plasticity in Leishmania and to investigate the adaptive role of aneuploidy in the colonization of two natural environments of Leishmania: the sandfly vector and mammal host.