What is it about?
Everything that was done before on the genome of Leishmania was done in an artificial system in vitro on promastigotes, the form of the parasite normally residing in the sandfly. Here we describe for the first time the all the changes that occurs in Leishmania genome during its life cycle with the best animal models available. Thor this we used hamsters as source of amastigotes, hamsters are the best model for spleen and liver diseases, and Phlebotomus argentipes, the natural vector of Leishmania donovani in the Indian subcontinent. We observed no changes on the sequence itself, meaning no apparition of DNA mutation, base changes or insertion/deletion neither amplification of some part of the genome. However we could see variation of the number of chromosomes with a noticeable decreasing trend when place inside a mammal but also that the passage inside the sandfly does not change the number of chromosomes of the parasite. In a second time we had a look at the expression since normally more chromosomes meaning a higher expression for all the genes of those chromosomes and decrease of expression when the number of chromosomes decrease. Would could confirm this for all the chromosomes expect one, chromosomes 31, but we also observed some genes that do not respect the expression level of their associated chromosome.
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Why is it important?
Leishmania is a parasite well known to play with its chromosome number to counter different stresses such as drug pressure. In a previous study, in Imamura et al. 2016 we could not find any correlation between chromosome copy number and drug resistant phenotype or drug failure. This might be explained because we were investigating the question with DNA coming from in vitro promastigotes. Now that we know the number of chromosomes inside the mammalian host is very different than in vitro, we have to revisit this paradigm with this new knowledge
Perspectives
As said previously, this study led us to understand some question, like do we always observe less Leishmania DNA in a patient sample than with the same number of in vitro parasites. Now we know that inside the mammalian host the parasite has less chromomes so less DNA. We could also look at the genetic diversity described in Imamura et al. to maybe find a correlation between the karyotype and the phenotype. For this, we have 2 different options, either we perform the same type of study as we did here or we try to develop in situ sequencing to directly sequence the parasite DNA directly coming from the spleen, liver or bone marrow from the host.
Dr Franck Dumetz
University of Maryland
Read the Original
This page is a summary of: Modulation of Aneuploidy in Leishmania donovani during Adaptation to Different In Vitro and In Vivo Environments and Its Impact on Gene Expression, mBio, May 2017, ASM Journals,
DOI: 10.1128/mbio.00599-17.
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