Project #17724
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#17724 : Gene conversion and allelic selection drives L. donovani genomic adaptation in experimental Sand fly infection
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Name of Applicant : Gerald Spaeth
Date of application : 18-11-2021
Unit : Molecular Parasitology and Signaling
Location : Calmette 2nd floor
Phone : 3858
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Project context and summary :

Leishmania genomic adaptation during sand fly infection is only poorly understood. In particular, the possibility of allelic selection in a given parasite population inside the insect vector has not been investigated, even though sexual recombination and the possibly of self-sex (selfing) can change allele frequencies and thus may be relevant for parasite transmission and virulence. We investigate this important open question conducting experimental sand fly infection with bona fide amastigotes isolated from infected hamster spleen, and derived promastigotes with different karyotypic profiles. Applying our genome instability pipeline (GIP) on sand fly-recovered parasites revealed a novel form of Leishmania genome instability inside the insect vector relying on gene conversion, which causes haplotype shuffling and likely allows for the selection of beneficial alleles.

Related team publications :
Bussotti G, Benkahla A, Jeddi F, Souiaï O, Aoun K, Späth GF, Bouratbine A. Nuclear and mitochondrial genome sequencing of North-African Leishmania infantum isolates from cured and relapsed visceral leishmaniasis patients reveals variations correlating with geography and phenotype. Microb Genom. 2020 Oct;6(10):mgen000444. doi: 10.1099/mgen.0.000444. PMID: 32975503; PMCID: PMC7660250.
Prieto Barja P, Pescher P, Bussotti G, Dumetz F, Imamura H, Kedra D, Domagalska M, Chaumeau V, Himmelbauer H, Pages M, Sterkers Y, Dujardin JC, Notredame C, Späth GF. Haplotype selection as an adaptive mechanism in the protozoan pathogen Leishmania donovani. Nat Ecol Evol. 2017 Dec;1(12):1961-1969. doi: 10.1038/s41559-017-0361-x. Epub 2017 Nov 6. PMID: 29109466.
Bussotti G, Gouzelou E, Côrtes Boité M, Kherachi I, Harrat Z, Eddaikra N, Mottram JC, Antoniou M, Christodoulou V, Bali A, Guerfali FZ, Laouini D, Mukhtar M, Dumetz F, Dujardin JC, Smirlis D, Lechat P, Pescher P, El Hamouchi A, Lemrani M, Chicharro C, Llanes-Acevedo IP, Botana L, Cruz I, Moreno J, Jeddi F, Aoun K, Bouratbine A, Cupolillo E, Späth GF. Leishmania Genome Dynamics during Environmental Adaptation Reveal Strain-Specific Differences in Gene Copy Number Variation, Karyotype Instability, and Telomeric Amplification. mBio. 2018 Nov 6;9(6):e01399-18. doi: 10.1128/mBio.01399-18. PMID: 30401775; PMCID: PMC6222132.
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Project Type : Medium
Status : In Progress

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