<italic toggle="yes">Leishmania</italic> Genome Dynamics during Environmental Adaptation Reveal Strain-Specific Differences in Gene Copy Number Variation, Karyotype Instability, and Telomeric Amplification
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 Leishm...
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2018-12-01
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| Series: | mBio |
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| Online Access: | https://journals.asm.org/doi/10.1128/mBio.01399-18 |
| _version_ | 1818402014350016512 |
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| author | Giovanni Bussotti Evi Gouzelou Mariana Côrtes Boité Ihcen Kherachi Zoubir Harrat Naouel Eddaikra Jeremy C. Mottram Maria Antoniou Vasiliki Christodoulou Aymen Bali Fatma Z. Guerfali Dhafer Laouini Maowia Mukhtar Franck Dumetz Jean-Claude Dujardin Despina Smirlis Pierre Lechat Pascale Pescher Adil El Hamouchi Meryem Lemrani Carmen Chicharro Ivonne Pamela Llanes-Acevedo Laura Botana Israel Cruz Javier Moreno Fakhri Jeddi Karim Aoun Aïda Bouratbine Elisa Cupolillo Gerald F. Späth |
| author_facet | Giovanni Bussotti Evi Gouzelou Mariana Côrtes Boité Ihcen Kherachi Zoubir Harrat Naouel Eddaikra Jeremy C. Mottram Maria Antoniou Vasiliki Christodoulou Aymen Bali Fatma Z. Guerfali Dhafer Laouini Maowia Mukhtar Franck Dumetz Jean-Claude Dujardin Despina Smirlis Pierre Lechat Pascale Pescher Adil El Hamouchi Meryem Lemrani Carmen Chicharro Ivonne Pamela Llanes-Acevedo Laura Botana Israel Cruz Javier Moreno Fakhri Jeddi Karim Aoun Aïda Bouratbine Elisa Cupolillo Gerald F. Späth |
| author_sort | Giovanni Bussotti |
| collection | DOAJ |
| description | 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. IMPORTANCE 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. |
| first_indexed | 2024-12-14T08:01:37Z |
| format | Article |
| id | doaj.art-56d904b3382f42ed88d1c4dbf455eff6 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-12-14T08:01:37Z |
| publishDate | 2018-12-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-56d904b3382f42ed88d1c4dbf455eff62022-12-21T23:10:22ZengAmerican Society for MicrobiologymBio2150-75112018-12-019610.1128/mBio.01399-18<italic toggle="yes">Leishmania</italic> Genome Dynamics during Environmental Adaptation Reveal Strain-Specific Differences in Gene Copy Number Variation, Karyotype Instability, and Telomeric AmplificationGiovanni Bussotti0Evi Gouzelou1Mariana Côrtes Boité2Ihcen Kherachi3Zoubir Harrat4Naouel Eddaikra5Jeremy C. Mottram6Maria Antoniou7Vasiliki Christodoulou8Aymen Bali9Fatma Z. Guerfali10Dhafer Laouini11Maowia Mukhtar12Franck Dumetz13Jean-Claude Dujardin14Despina Smirlis15Pierre Lechat16Pascale Pescher17Adil El Hamouchi18Meryem Lemrani19Carmen Chicharro20Ivonne Pamela Llanes-Acevedo21Laura Botana22Israel Cruz23Javier Moreno24Fakhri Jeddi25Karim Aoun26Aïda Bouratbine27Elisa Cupolillo28Gerald F. Späth29Institut Pasteur—Bioinformatics and Biostatistics Hub—C3BI, USR 3756 IP CNRS, Paris, FranceUnité de Parasitologiemoléculaire et Signalisation, Institut Pasteur, Paris, FranceLaboratory on Leishmaniasis Research, Oswaldo Cruz Institute—Fiocruz, Rio de Janeiro, BrazilLaboratoire d’Eco-épidémiologieparasitaire et Génétique des Populations, Institut Pasteur d’Algérie, Algiers, AlgériaLaboratoire d’Eco-épidémiologieparasitaire et Génétique des Populations, Institut Pasteur d’Algérie, Algiers, AlgériaLaboratoire d’Eco-épidémiologieparasitaire et Génétique des Populations, Institut Pasteur d’Algérie, Algiers, AlgériaCentre for Immunology and Infection, Department of Biology, University of York, York, United KingdomLaboratory of Clinical Bacteriology, Parasitology, Zoonoses and Geographical Medicine, School of Medicine, University of Crete, VassilikaVouton, Heraklion, GreeceLaboratory of Clinical Bacteriology, Parasitology, Zoonoses and Geographical Medicine, School of Medicine, University of Crete, VassilikaVouton, Heraklion, GreeceLaboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, Tunis-Belvédère, TunisiaLaboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, Tunis-Belvédère, TunisiaLaboratory of Transmission, Control and Immunobiology of Infections (LTCII), Institut Pasteur de Tunis, Tunis-Belvédère, TunisiaThe Institute of Endemic Diseases, University of Khartoum, Khartoum, SudanMolecular Parasitology Unit, Institute of Tropical Medicine, Antwerp, BelgiumMolecular Parasitology Unit, Institute of Tropical Medicine, Antwerp, BelgiumMolecular Parasitology Laboratory, Microbiology Department, Hellenic Pasteur Institute, Athens, GreeceInstitut Pasteur—Bioinformatics and Biostatistics Hub—C3BI, USR 3756 IP CNRS, Paris, FranceUnité de Parasitologiemoléculaire et Signalisation, Institut Pasteur, Paris, FranceLaboratory of Parasitology and Vector-Borne-Diseases, Institut Pasteur du Maroc, Casablanca, MoroccoLaboratory of Parasitology and Vector-Borne-Diseases, Institut Pasteur du Maroc, Casablanca, MoroccoWHO Collaborating Centre for Leishmaniasis, Instituto de Salud Carlos III, Madrid, SpainWHO Collaborating Centre for Leishmaniasis, Instituto de Salud Carlos III, Madrid, SpainWHO Collaborating Centre for Leishmaniasis, Instituto de Salud Carlos III, Madrid, SpainWHO Collaborating Centre for Leishmaniasis, Instituto de Salud Carlos III, Madrid, SpainWHO Collaborating Centre for Leishmaniasis, Instituto de Salud Carlos III, Madrid, SpainUniversité Tunis El Manar, Tunis, TunisiaUniversité Tunis El Manar, Tunis, TunisiaUniversité Tunis El Manar, Tunis, TunisiaLaboratory on Leishmaniasis Research, Oswaldo Cruz Institute—Fiocruz, Rio de Janeiro, BrazilUnité de Parasitologiemoléculaire et Signalisation, Institut Pasteur, Paris, FranceABSTRACT 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. IMPORTANCE 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.https://journals.asm.org/doi/10.1128/mBio.01399-18Leishmaniaaneuploidyevolutiongene copy number variationgenomic adaptationtelomeric amplification |
| spellingShingle | Giovanni Bussotti Evi Gouzelou Mariana Côrtes Boité Ihcen Kherachi Zoubir Harrat Naouel Eddaikra Jeremy C. Mottram Maria Antoniou Vasiliki Christodoulou Aymen Bali Fatma Z. Guerfali Dhafer Laouini Maowia Mukhtar Franck Dumetz Jean-Claude Dujardin Despina Smirlis Pierre Lechat Pascale Pescher Adil El Hamouchi Meryem Lemrani Carmen Chicharro Ivonne Pamela Llanes-Acevedo Laura Botana Israel Cruz Javier Moreno Fakhri Jeddi Karim Aoun Aïda Bouratbine Elisa Cupolillo Gerald F. Späth <italic toggle="yes">Leishmania</italic> Genome Dynamics during Environmental Adaptation Reveal Strain-Specific Differences in Gene Copy Number Variation, Karyotype Instability, and Telomeric Amplification mBio Leishmania aneuploidy evolution gene copy number variation genomic adaptation telomeric amplification |
| title | <italic toggle="yes">Leishmania</italic> Genome Dynamics during Environmental Adaptation Reveal Strain-Specific Differences in Gene Copy Number Variation, Karyotype Instability, and Telomeric Amplification |
| title_full | <italic toggle="yes">Leishmania</italic> Genome Dynamics during Environmental Adaptation Reveal Strain-Specific Differences in Gene Copy Number Variation, Karyotype Instability, and Telomeric Amplification |
| title_fullStr | <italic toggle="yes">Leishmania</italic> Genome Dynamics during Environmental Adaptation Reveal Strain-Specific Differences in Gene Copy Number Variation, Karyotype Instability, and Telomeric Amplification |
| title_full_unstemmed | <italic toggle="yes">Leishmania</italic> Genome Dynamics during Environmental Adaptation Reveal Strain-Specific Differences in Gene Copy Number Variation, Karyotype Instability, and Telomeric Amplification |
| title_short | <italic toggle="yes">Leishmania</italic> Genome Dynamics during Environmental Adaptation Reveal Strain-Specific Differences in Gene Copy Number Variation, Karyotype Instability, and Telomeric Amplification |
| title_sort | italic toggle yes leishmania italic genome dynamics during environmental adaptation reveal strain specific differences in gene copy number variation karyotype instability and telomeric amplification |
| topic | Leishmania aneuploidy evolution gene copy number variation genomic adaptation telomeric amplification |
| url | https://journals.asm.org/doi/10.1128/mBio.01399-18 |
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