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LEISHMANIA GENOME DYNAMICS DURING ENVIRONMENTAL ADAPTATION REVEAL STRAIN-SPECIfiC DIFFERENCES IN GENE COPY NUMBER VARIATION, KARYOTYPE INSTABILITY, AND TELOMERIC AMPLIfiCATION
Evolução
Variação do número da cópia do gene
Adaptação genômica
Aneuploidia
Amplificação de Telômetos
Evolution
Gene copy number variation
Genomic adaptation
Telomeric amplification
Aneuploidy
Author
Bussotti, Giovanni
Gouzelou, Evi
Aoun, Karim
Bouratbine, Aïda
Cupolillo, Elisa
Späthb, Gerald F.
Kherachi, Ihcen
Harrat, Zoubir
Eddaikra, Naouel
Mottran, Jeremy C.
Antoniou, Maria
Christodoulou, Vasiliki
Bali, Aymen
Guerfali, Fatima Z.
Laouini, Dhafer
Mukhtar, Maowia
Dumetz, Franck
Dujardim, Jean-Claude
Smirlis, Despina
Lechar, Pierre
Pescher, Pascale
El Hamouchi, Adil
Lemrani, Meryem
Chicharro, Carmen
Llanes-Acevedo, Ivonne Pamela
Botana, Laura
Cruz, Israel
Boité, Mariana Côrtes
Moreno, Javier
Jeddi, Fakhn
Gouzelou, Evi
Aoun, Karim
Bouratbine, Aïda
Cupolillo, Elisa
Späthb, Gerald F.
Kherachi, Ihcen
Harrat, Zoubir
Eddaikra, Naouel
Mottran, Jeremy C.
Antoniou, Maria
Christodoulou, Vasiliki
Bali, Aymen
Guerfali, Fatima Z.
Laouini, Dhafer
Mukhtar, Maowia
Dumetz, Franck
Dujardim, Jean-Claude
Smirlis, Despina
Lechar, Pierre
Pescher, Pascale
El Hamouchi, Adil
Lemrani, Meryem
Chicharro, Carmen
Llanes-Acevedo, Ivonne Pamela
Botana, Laura
Cruz, Israel
Boité, Mariana Côrtes
Moreno, Javier
Jeddi, Fakhn
Affilliation
Institut Pasteur. Bioinformatics and Biostatistics Hub. Paris, France / Institute Pasteur. Unité de Parasitologiemoléculaire et Signalisation. Paris, France.
Institute Pasteur. Unité de Parasitologiemoléculaire et Signalisation. Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose. Rio de Janeiro, RJ, Brasil.
Institut Pasteur d’Algérie. Laboratoire d’Eco-épidémiologieparasitaire et Génétique des Populations, Algiers, Algéria.
Institut Pasteur d’Algérie. Laboratoire d’Eco-épidémiologieparasitaire et Génétique des Populations, Algiers, Algéria.
Institut Pasteur d’Algérie. Laboratoire d’Eco-épidémiologieparasitaire et Génétique des Populations, Algiers, Algéria.
University of New York. Department of Biology. Centre for Immunology and Infection. New York, NY, USA.
Laboratory of Clinical Bacteriology, Parasitology, Zoonoses and Geographical Medicine. School of Medicine, University of Crete. VassilikaVouton, Heraklion, Greece.
Laboratory of Clinical Bacteriology, Parasitology, Zoonoses and Geographical Medicine. School of Medicine, University of Crete. VassilikaVouton, Heraklion, Greece.
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, Tunis-Belvédère, Tunisia / Université Tunis El Manar, Tunis, Tunisia.
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, Tunis-Belvédère, Tunisia / Université Tunis El Manar, Tunis, Tunisia.
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, Tunis-Belvédère, Tunisia / Université Tunis El Manar, Tunis, Tunisia.
The Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Institute of Tropical Medicine. Molecular Parasitology Unit, Antwerp, Belgium.
Institute of Tropical Medicine. Molecular Parasitology Unit, Antwerp, Belgium / University of Antwerp. Department of Biomedical Sciences. Antwerp, Belgium.
Hellenic Pasteur Institute. Molecular Parasitology Laboratory, Microbiology Department. Athens, Greece.
Institut Pasteur—Bioinformatics and Biostatistics Hub—C3BI, USR 3756 IP CNRS, Paris, France.
Unité de Parasitologiemoléculaire et Signalisation, Institut Pasteur, Paris, France.
Laboratory of Parasitology and Vector-Borne-Diseases, Institut Pasteur du Maroc, Casablanca, Morocco.
Laboratory of Parasitology and Vector-Borne-Diseases, Institut Pasteur du Marocco, Casablanca, Morocco.
WHO Collaborating Centre for Leishmaniasis, Instituto de Salud Carlos III. Madrid, Spain.
WHO Collaborating Centre for Leishmaniasis, Instituto de Salud Carlos III. Madrid, Spain.
WHO Collaborating Centre for Leishmaniasis, Instituto de Salud Carlos III. Madrid, Spain.
WHO Collaborating Centre for Leishmaniasis, Instituto de Salud Carlos III. Madrid, Spain.
WHO Collaborating Centre for Leishmaniasis, Instituto de Salud Carlos III. Madrid, Spain.
Université Tunis El Manar, Tunis, Tunisia / Research Laboratory Medical Parasitology, Biotechnology and Biomolecules, Institut Pasteur de Tunis. Tunis-Belvédère, Tunisia.
Université Tunis El Manar, Tunis, Tunisia / Research Laboratory Medical Parasitology, Biotechnology and Biomolecules, Institut Pasteur de Tunis. Tunis-Belvédère, Tunisia.
Université Tunis El Manar, Tunis, Tunisia / Research Laboratory Medical Parasitology, Biotechnology and Biomolecules, Institut Pasteur de Tunis. Tunis-Belvédère, Tunisia.
Fundação Oswaldo Cruz. Instituto Oswaldo Oruz. Laboratório de Pesquisa em Leishmaniose. Rio de Janeiro, RJ, Brasil.
Institut Pasteur. Unité de Parasitologiemoléculaire et Signalisation, Paris, France.
Institute Pasteur. Unité de Parasitologiemoléculaire et Signalisation. Paris, France.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Pesquisa em Leishmaniose. Rio de Janeiro, RJ, Brasil.
Institut Pasteur d’Algérie. Laboratoire d’Eco-épidémiologieparasitaire et Génétique des Populations, Algiers, Algéria.
Institut Pasteur d’Algérie. Laboratoire d’Eco-épidémiologieparasitaire et Génétique des Populations, Algiers, Algéria.
Institut Pasteur d’Algérie. Laboratoire d’Eco-épidémiologieparasitaire et Génétique des Populations, Algiers, Algéria.
University of New York. Department of Biology. Centre for Immunology and Infection. New York, NY, USA.
Laboratory of Clinical Bacteriology, Parasitology, Zoonoses and Geographical Medicine. School of Medicine, University of Crete. VassilikaVouton, Heraklion, Greece.
Laboratory of Clinical Bacteriology, Parasitology, Zoonoses and Geographical Medicine. School of Medicine, University of Crete. VassilikaVouton, Heraklion, Greece.
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, Tunis-Belvédère, Tunisia / Université Tunis El Manar, Tunis, Tunisia.
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, Tunis-Belvédère, Tunisia / Université Tunis El Manar, Tunis, Tunisia.
Laboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, Tunis-Belvédère, Tunisia / Université Tunis El Manar, Tunis, Tunisia.
The Institute of Endemic Diseases, University of Khartoum, Khartoum, Sudan.
Institute of Tropical Medicine. Molecular Parasitology Unit, Antwerp, Belgium.
Institute of Tropical Medicine. Molecular Parasitology Unit, Antwerp, Belgium / University of Antwerp. Department of Biomedical Sciences. Antwerp, Belgium.
Hellenic Pasteur Institute. Molecular Parasitology Laboratory, Microbiology Department. Athens, Greece.
Institut Pasteur—Bioinformatics and Biostatistics Hub—C3BI, USR 3756 IP CNRS, Paris, France.
Unité de Parasitologiemoléculaire et Signalisation, Institut Pasteur, Paris, France.
Laboratory of Parasitology and Vector-Borne-Diseases, Institut Pasteur du Maroc, Casablanca, Morocco.
Laboratory of Parasitology and Vector-Borne-Diseases, Institut Pasteur du Marocco, Casablanca, Morocco.
WHO Collaborating Centre for Leishmaniasis, Instituto de Salud Carlos III. Madrid, Spain.
WHO Collaborating Centre for Leishmaniasis, Instituto de Salud Carlos III. Madrid, Spain.
WHO Collaborating Centre for Leishmaniasis, Instituto de Salud Carlos III. Madrid, Spain.
WHO Collaborating Centre for Leishmaniasis, Instituto de Salud Carlos III. Madrid, Spain.
WHO Collaborating Centre for Leishmaniasis, Instituto de Salud Carlos III. Madrid, Spain.
Université Tunis El Manar, Tunis, Tunisia / Research Laboratory Medical Parasitology, Biotechnology and Biomolecules, Institut Pasteur de Tunis. Tunis-Belvédère, Tunisia.
Université Tunis El Manar, Tunis, Tunisia / Research Laboratory Medical Parasitology, Biotechnology and Biomolecules, Institut Pasteur de Tunis. Tunis-Belvédère, Tunisia.
Université Tunis El Manar, Tunis, Tunisia / Research Laboratory Medical Parasitology, Biotechnology and Biomolecules, Institut Pasteur de Tunis. Tunis-Belvédère, Tunisia.
Fundação Oswaldo Cruz. Instituto Oswaldo Oruz. Laboratório de Pesquisa em Leishmaniose. Rio de Janeiro, RJ, Brasil.
Institut Pasteur. Unité de Parasitologiemoléculaire et Signalisation, Paris, France.
Abstract
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.
Keywords in Portuguese
LeishmaniaEvolução
Variação do número da cópia do gene
Adaptação genômica
Aneuploidia
Amplificação de Telômetos
Keywords
LieshmaniaEvolution
Gene copy number variation
Genomic adaptation
Telomeric amplification
Aneuploidy
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