Leishmania genome dynamics during environmental adaptation reveals strain-and species-specific differences in karyotypic instability and telomere maintenance. Leishmania genome dynamics during environmental adaptation in culture

Protozoan parasites of the genus Leishmania cause severe human diseases worldwide. A hallmark of Leishmania infection is the parasite’s capacity to quickly adapt to environmental change through chromosome and gene copy number variations. Only little is known on external or intrinsic factors that govern Leishmania genome plasticity despite its important impact on the parasite pathogenic potential. Here we use de novo culture as a proxy to study and compare species- and strain-specific differences in Leishmania genomic adaptation. Whole genome sequencing analysis of four different Leishmania species isolated from clinical samples across eight geographical regions confirms chromosomal amplification as a major driver of parasite adaptation to environmental change. Karyotypic solutions to culture adaptation were reproducible for each given strain but showed important differences between isolates revealing species- and even strain-specific intrinsic factors underlying Leishmania evolvability. Read depth analyses did not show any significant gene copy number variation during early culture adaptation, but uncovered a novel mechanism of Leishmania telomere maintenance through genome-wide, sub-telomeric amplification that likely preserves telomere integrity during selection for fast in vitro growth. Together our data draw a complex picture of Leishmania genomic adaptation, which is driven by a combination of intrinsic genetic factors that generate strain-specific phenotypic variations, and external cues that select for fitness gains under different environmental constraints. Conceivably, such a highly individualized, genomic responses to the same environmental challenge likely operates in the field, highlighting the major difficulty to discover Leishmania biomarkers with broad diagnostic or prognostic value.