Leishmaniasis is an important human and veterinary disease caused by Leishmania parasites that affect 12 million people in over 98 endemic countries. The disease is now emerging in Europe due to climate change and massive population displacement. The parasite is known to rapidly adapt to novel environments with important consequences for disease outcome. It has therefore been recognized as an emerging public health threat for the EU.
In a paper, published in Nature Ecology & Evolution, scientists from the Institut Pasteur in Paris and the Centre for Genomic Regulation (CRG) in Barcelona, in collaboration with teams at the Institute of Tropical Medicine Antwerp (ITM) and the University of Montpellier, have now demonstrated that Leishmania adaptation results from frequent and reversible chromosomal amplifications. Such variations, named aneuploidies, are similar to those occurring in many cancer types.
These findings represent an important step towards a better understanding of human Leishmania infection, with relevance to parasite drug resistance, pathogenicity, and tissue tropism. This novel insight into Leishmania genomic instability should pave the way for the identification of parasite drug resistance mechanisms in clinically relevant settings and help discover biomarkers with diagnostic and prognostic value.
To identify the genetic mechanisms that drive Leishmania genomic adaptation, scientists from the Institut Pasteur in Paris and the Centre for Genomic Regulation (CRG) in Barcelona, in collaboration with teams at the Institute of Tropical Medicine Antwerp (ITM) and the University of Montpellier have developed novel techniques for comparative genomics, based on next generation sequencing and in-silico analyses. Their work, which is published in Nature Ecology and Evolution, shows for the first time the existence in Leishmania of a relation between changes in chromosome copy number and the selection of new alleles important for parasite survival.
The most surprising aspect of this work is the observation that Leishmania manages to combine allele selection with the maintenance of a high genetic diversity. Normally these two processes should be mutually exclusive, and one would expect a parasite under strong selection to rapidly lose its genetic diversity. In Leishmania, however, the very frequent chromosomal duplications make it possible to combine both. Indeed, the parasite maintains its diversity by allowing the same combination of alleles to be selected simultaneously in genetically diverse individuals.