Leishmania genome dynamics during environmental adaptation reveals strain-specific differences in gene copy number variation, karyotype instability, and telomeric amplification
| Autor: | Fakhri Jeddi, Vasiliki Christodoulou, Naouel Eddaikra, Javier Moreno, Carmen Chicharro, Pascale Pescher, Ihcen Kherachi, Laura Botana, Ivonne Pamela Llanes-Acevedo, Gerald F. Späth, Jean-Claude Dujardin, Despina Smirlis, Aymen Bali, Evi Gouzelou, Pierre Lechat, Israel Cruz, Zoubir Harrat, Maowla Mukhtar, Dhafer Laouini, Jeremy C. Mottram, Maria Antoniou, Giovanni Bussotti, Karim Aoun, Fatma Z. Guerfali, Aïda Bouratbine, Elisa Cupolillo, Meryem Lemrani, Mariana Côrtes Boité, Franck Dumetz, Adil El Hamouchi |
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| Přispěvatelé: | Parasitologie moléculaire et Signalisation / Molecular Parasitology and Signaling, Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur [Paris], Hub Bioinformatique et Biostatistique - Bioinformatics and Biostatistics HUB, Institut Pasteur [Paris]-Centre National de la Recherche Scientifique (CNRS), Fundação Oswaldo Cruz (FIOCRUZ), Réseau International des Instituts Pasteur (RIIP), Institut Pasteur d'Algérie, University of York [York, UK], University of Crete [Heraklion] (UOC), Laboratoire de Transmission, Contrôle et Immunobiologie des Infections - Laboratory of Transmission, Control and Immunobiology of Infection (LR11IPT02), Institut Pasteur de Tunis, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Université de Tunis El Manar (UTM), University of Khartoum, Institute of Tropical Medicine [Antwerp] (ITM), University of Antwerp (UA), Institut Pasteur Hellénique, Institut Pasteur du Maroc, Instituto de Salud Carlos III [Madrid] (ISC), Laboratoire de Parasitologie Médicale, Biotechnologies et Biomolécules (LR11IPT06), This study was supported by a seeding grant from the Institut Pasteur International Department to the LeiSHield Consortium, the EU FP7 (Kaladrug-R, contract 222895), the Belgian Science Policy Office (TRIT, P7/41), the Department of Economy, Science and Innovation in Flanders (ITM-SOFIB), and the Flemish Fund for Scientific Research (G.0.B81.12 to J.C.D. and F.D.)., European Project: 222895,EC:FP7:HEALTH,FP7-HEALTH-2007-B,KALADRUG-R(2008), Belgian Science Policy Office, Unión Europea, Institut Pasteur [Paris] (IP)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Pasteur [Paris] (IP)-Centre National de la Recherche Scientifique (CNRS), Fundação Oswaldo Cruz / Oswaldo Cruz Foundation (FIOCRUZ), Mottram, Jeremy C [0000-0001-5574-3766], Dumetz, Franck [0000-0001-8790-9986], Apollo - University of Cambridge Repository |
| Jazyk: | angličtina |
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Genomic adaptation [SDV]Life Sciences [q-bio] Genes Protozoan Gene Dosage gene copy number variation Genome 0302 clinical medicine Cricetinae Gene duplication Copy-number variation Genetics Regulation of gene expression Leishmania biology High-Throughput Nucleotide Sequencing Genomics Telomere Adaptation Physiological QR1-502 3. Good health Leishmaniasis Visceral Gene copy number variation Research Article Telomeric amplification DNA Copy Number Variations Evolution Karyotype Ecological and Evolutionary Science Microbiology Chromosomes Evolution Molecular 03 medical and health sciences Dogs Virology parasitic diseases evolution Animals Humans aneuploidy Gene Biology Comparative genomics genomic adaptation Gene Amplification biology.organism_classification Aneuploidy telomeric amplification 030104 developmental biology Gene Expression Regulation Genetic Fitness Adaptation Genome Protozoan 030217 neurology & neurosurgery Leishmania donovani |
| Zdroj: | mBio, Vol 9, Iss 6 (2018) mBio mBio, American Society for Microbiology, 2018, 9 (6), pp.e01399-18. ⟨10.1128/mBio.01399-18⟩ Repisalud Instituto de Salud Carlos III (ISCIII) mBio, Vol 9, Iss 6, p e01399-18 (2018) mBio, 2018, 9 (6), pp.e01399-18. ⟨10.1128/mBio.01399-18⟩ |
| ISSN: | 2150-7511 2161-2129 |
| Popis: | Protozoan parasites of the genus Leishmania cause severe human and veterinary diseases worldwide, termed leishmaniases. A hallmark of Leishmania biology is its capacity to adapt to a variety of unpredictable fluctuations inside its human host, notably pharmacological interventions, thus, causing drug resistance. Here we investigated mechanisms of environmental adaptation using a comparative genomics approach by sequencing 10 new clinical isolates of the L. donovani, L. major, and L. tropica complexes that were sampled across eight distinct geographical regions. Our data provide new evidence that parasites adapt to environmental change in the field and in culture through a combination of chromosome and gene amplification that likely causes phenotypic variation and drives parasite fitness gains in response to environmental constraints. This novel form of gene expression regulation through genomic change compensates for the absence of classical transcriptional control in these early-branching eukaryotes and opens new venues for biomarker discovery. Protozoan parasites of the genus Leishmania adapt to environmental change through chromosome and gene copy number variations. Only little is known about external or intrinsic factors that govern Leishmania genomic adaptation. Here, by conducting longitudinal genome analyses of 10 new Leishmania clinical isolates, we uncovered important differences in gene copy number among genetically highly related strains and revealed gain and loss of gene copies as potential drivers of long-term environmental adaptation in the field. In contrast, chromosome rather than gene amplification was associated with short-term environmental adaptation to in vitro culture. Karyotypic solutions were highly reproducible but unique for a given strain, suggesting that chromosome amplification is under positive selection and dependent on species- and strain-specific intrinsic factors. We revealed a progressive increase in read depth towards the chromosome ends for various Leishmania isolates, which may represent a nonclassical mechanism of telomere maintenance that can preserve integrity of chromosome ends during selection for fast in vitro growth. Together our data draw a complex picture of Leishmania genomic adaptation in the field and in culture, which is driven by a combination of intrinsic genetic factors that generate strain-specific phenotypic variations, which are under environmental selection and allow for fitness gain. |
| Databáze: | OpenAIRE |
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