Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes
Identifieur interne : 000C02 ( Main/Exploration ); précédent : 000C01; suivant : 000C03Functional Profiling of a Plasmodium Genome Reveals an Abundance of Essential Genes
Auteurs : Ellen Bushell [Royaume-Uni] ; Ana Rita Gomes [Royaume-Uni] ; Theo Sanderson [Royaume-Uni] ; Burcu Anar [Royaume-Uni] ; Gareth Girling [Royaume-Uni] ; Colin Herd [Royaume-Uni] ; Tom Metcalf [Royaume-Uni] ; Katarzyna Modrzynska [Royaume-Uni] ; Frank Schwach [Royaume-Uni] ; Rowena E. Martin [Australie] ; Michael W. Mather [États-Unis] ; Geoffrey I. Mcfadden [Australie] ; Leopold Parts [Royaume-Uni] ; Gavin G. Rutledge [Royaume-Uni] ; Akhil B. Vaidya [États-Unis] ; Kai Wengelnik [France] ; Julian C. Rayner [Royaume-Uni] ; Oliver Billker [Royaume-Uni]Source :
- Cell [ 0092-8674 ] ; 2017.
Descripteurs français
- KwdFr :
- Animaux, Femelle, Gènes essentiels, Génome de protozoaire, Interactions hôte-parasite, Plasmodium berghei (croissance et développement), Plasmodium berghei (génétique), Plasmodium berghei (métabolisme), Saccharomyces cerevisiae (génétique), Souris, Souris de lignée BALB C, Techniques de knock-out de gènes, Toxoplasma (génétique), Trypanosoma brucei brucei (génétique), Voies et réseaux métaboliques, Évolution biologique.
- MESH :
- croissance et développement : Plasmodium berghei.
- génétique : Plasmodium berghei, Saccharomyces cerevisiae, Toxoplasma, Trypanosoma brucei brucei.
- métabolisme : Plasmodium berghei.
- Animaux, Femelle, Gènes essentiels, Génome de protozoaire, Interactions hôte-parasite, Souris, Souris de lignée BALB C, Techniques de knock-out de gènes, Voies et réseaux métaboliques, Évolution biologique.
English descriptors
- KwdEn :
- Animals, Biological Evolution, Female, Gene Knockout Techniques, Genes, Essential, Genome, Protozoan, Host-Parasite Interactions, Metabolic Networks and Pathways, Mice, Mice, Inbred BALB C, Plasmodium berghei (genetics), Plasmodium berghei (growth & development), Plasmodium berghei (metabolism), Saccharomyces cerevisiae (genetics), Toxoplasma (genetics), Trypanosoma brucei brucei (genetics).
- MESH :
- genetics : Plasmodium berghei, Saccharomyces cerevisiae, Toxoplasma, Trypanosoma brucei brucei.
- growth & development : Plasmodium berghei.
- metabolism : Plasmodium berghei.
- Animals, Biological Evolution, Female, Gene Knockout Techniques, Genes, Essential, Genome, Protozoan, Host-Parasite Interactions, Metabolic Networks and Pathways, Mice, Mice, Inbred BALB C.
Abstract
The genomes of malaria parasites contain many genes of unknown function. To assist drug development through the identification of essential genes and pathways, we have measured competitive growth rates in mice of 2,578 barcoded
Url:
DOI: 10.1016/j.cell.2017.06.030
PubMed: 28708996
PubMed Central: 5509546
Affiliations:
- Australie, France, Royaume-Uni, États-Unis
- Languedoc-Roussillon, Occitanie (région administrative), Pennsylvanie, Victoria (État)
- Melbourne, Montpellier
- Université de Melbourne
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Le document en format XML
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UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire</wicri:regionArea><wicri:noRegion>Cambridgeshire</wicri:noRegion></affiliation></author><author><name sortKey="Gomes, Ana Rita" sort="Gomes, Ana Rita" uniqKey="Gomes A" first="Ana Rita" last="Gomes">Ana Rita Gomes</name><affiliation wicri:level="1"><nlm:aff id="aff1">Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire</wicri:regionArea><wicri:noRegion>Cambridgeshire</wicri:noRegion></affiliation></author><author><name sortKey="Sanderson, Theo" sort="Sanderson, Theo" uniqKey="Sanderson T" first="Theo" last="Sanderson">Theo Sanderson</name><affiliation wicri:level="1"><nlm:aff id="aff1">Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire</wicri:regionArea><wicri:noRegion>Cambridgeshire</wicri:noRegion></affiliation></author><author><name sortKey="Anar, Burcu" sort="Anar, Burcu" uniqKey="Anar B" first="Burcu" last="Anar">Burcu Anar</name><affiliation wicri:level="1"><nlm:aff id="aff1">Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire</wicri:regionArea><wicri:noRegion>Cambridgeshire</wicri:noRegion></affiliation></author><author><name sortKey="Girling, Gareth" sort="Girling, Gareth" uniqKey="Girling G" first="Gareth" last="Girling">Gareth Girling</name><affiliation wicri:level="1"><nlm:aff id="aff1">Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire</wicri:regionArea><wicri:noRegion>Cambridgeshire</wicri:noRegion></affiliation></author><author><name sortKey="Herd, Colin" sort="Herd, Colin" uniqKey="Herd C" first="Colin" last="Herd">Colin Herd</name><affiliation wicri:level="1"><nlm:aff id="aff1">Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire</wicri:regionArea><wicri:noRegion>Cambridgeshire</wicri:noRegion></affiliation></author><author><name sortKey="Metcalf, Tom" sort="Metcalf, Tom" uniqKey="Metcalf T" first="Tom" last="Metcalf">Tom Metcalf</name><affiliation wicri:level="1"><nlm:aff id="aff1">Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire</wicri:regionArea><wicri:noRegion>Cambridgeshire</wicri:noRegion></affiliation></author><author><name sortKey="Modrzynska, Katarzyna" sort="Modrzynska, Katarzyna" uniqKey="Modrzynska K" first="Katarzyna" last="Modrzynska">Katarzyna Modrzynska</name><affiliation wicri:level="1"><nlm:aff id="aff1">Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire</wicri:regionArea><wicri:noRegion>Cambridgeshire</wicri:noRegion></affiliation></author><author><name sortKey="Schwach, Frank" sort="Schwach, Frank" uniqKey="Schwach F" first="Frank" last="Schwach">Frank Schwach</name><affiliation wicri:level="1"><nlm:aff id="aff1">Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire</wicri:regionArea><wicri:noRegion>Cambridgeshire</wicri:noRegion></affiliation></author><author><name sortKey="Martin, Rowena E" sort="Martin, Rowena E" uniqKey="Martin R" first="Rowena E." last="Martin">Rowena E. Martin</name><affiliation wicri:level="1"><nlm:aff id="aff2">Research School of Biology, Australian National University, Canberra, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>Research School of Biology, Australian National University, Canberra</wicri:regionArea><wicri:noRegion>Canberra</wicri:noRegion></affiliation></author><author><name sortKey="Mather, Michael W" sort="Mather, Michael W" uniqKey="Mather M" first="Michael W." last="Mather">Michael W. Mather</name><affiliation wicri:level="2"><nlm:aff id="aff3">Drexel University College of Medicine, Philadelphia, PA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Drexel University College of Medicine, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Mcfadden, Geoffrey I" sort="Mcfadden, Geoffrey I" uniqKey="Mcfadden G" first="Geoffrey I." last="Mcfadden">Geoffrey I. Mcfadden</name><affiliation wicri:level="4"><nlm:aff id="aff4">School of Biosciences, University of Melbourne, Royal Parade, Parkville, Australia</nlm:aff><country xml:lang="fr">Australie</country><wicri:regionArea>School of Biosciences, University of Melbourne, Royal Parade, Parkville</wicri:regionArea><orgName type="university">Université de Melbourne</orgName><placeName><settlement type="city">Melbourne</settlement><region type="état">Victoria (État)</region></placeName></affiliation></author><author><name sortKey="Parts, Leopold" sort="Parts, Leopold" uniqKey="Parts L" first="Leopold" last="Parts">Leopold Parts</name><affiliation wicri:level="1"><nlm:aff id="aff1">Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire</wicri:regionArea><wicri:noRegion>Cambridgeshire</wicri:noRegion></affiliation></author><author><name sortKey="Rutledge, Gavin G" sort="Rutledge, Gavin G" uniqKey="Rutledge G" first="Gavin G." last="Rutledge">Gavin G. Rutledge</name><affiliation wicri:level="1"><nlm:aff id="aff1">Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire</wicri:regionArea><wicri:noRegion>Cambridgeshire</wicri:noRegion></affiliation></author><author><name sortKey="Vaidya, Akhil B" sort="Vaidya, Akhil B" uniqKey="Vaidya A" first="Akhil B." last="Vaidya">Akhil B. Vaidya</name><affiliation wicri:level="2"><nlm:aff id="aff3">Drexel University College of Medicine, Philadelphia, PA, USA</nlm:aff><country xml:lang="fr">États-Unis</country><wicri:regionArea>Drexel University College of Medicine, Philadelphia, PA</wicri:regionArea><placeName><region type="state">Pennsylvanie</region></placeName></affiliation></author><author><name sortKey="Wengelnik, Kai" sort="Wengelnik, Kai" uniqKey="Wengelnik K" first="Kai" last="Wengelnik">Kai Wengelnik</name><affiliation wicri:level="3"><nlm:aff id="aff5">DIMNP, CNRS, INSERM, University Montpellier, Montpellier, France</nlm:aff><country xml:lang="fr">France</country><wicri:regionArea>DIMNP, CNRS, INSERM, University Montpellier, Montpellier</wicri:regionArea><placeName><region type="region">Occitanie (région administrative)</region><region type="old region">Languedoc-Roussillon</region><settlement type="city">Montpellier</settlement></placeName></affiliation></author><author><name sortKey="Rayner, Julian C" sort="Rayner, Julian C" uniqKey="Rayner J" first="Julian C." last="Rayner">Julian C. Rayner</name><affiliation wicri:level="1"><nlm:aff id="aff1">Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire</wicri:regionArea><wicri:noRegion>Cambridgeshire</wicri:noRegion></affiliation></author><author><name sortKey="Billker, Oliver" sort="Billker, Oliver" uniqKey="Billker O" first="Oliver" last="Billker">Oliver Billker</name><affiliation wicri:level="1"><nlm:aff id="aff1">Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire, UK</nlm:aff><country xml:lang="fr">Royaume-Uni</country><wicri:regionArea>Wellcome Trust Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridgeshire</wicri:regionArea><wicri:noRegion>Cambridgeshire</wicri:noRegion></affiliation></author></analytic><series><title level="j">Cell</title><idno type="ISSN">0092-8674</idno><idno type="eISSN">1097-4172</idno><imprint><date when="2017">2017</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Animals</term><term>Biological Evolution</term><term>Female</term><term>Gene Knockout Techniques</term><term>Genes, Essential</term><term>Genome, Protozoan</term><term>Host-Parasite Interactions</term><term>Metabolic Networks and Pathways</term><term>Mice</term><term>Mice, Inbred BALB C</term><term>Plasmodium berghei (genetics)</term><term>Plasmodium berghei (growth & development)</term><term>Plasmodium berghei (metabolism)</term><term>Saccharomyces cerevisiae (genetics)</term><term>Toxoplasma (genetics)</term><term>Trypanosoma brucei brucei (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Animaux</term><term>Femelle</term><term>Gènes essentiels</term><term>Génome de protozoaire</term><term>Interactions hôte-parasite</term><term>Plasmodium berghei (croissance et développement)</term><term>Plasmodium berghei (génétique)</term><term>Plasmodium berghei (métabolisme)</term><term>Saccharomyces cerevisiae (génétique)</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Techniques de knock-out de gènes</term><term>Toxoplasma (génétique)</term><term>Trypanosoma brucei brucei (génétique)</term><term>Voies et réseaux métaboliques</term><term>Évolution biologique</term></keywords><keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Plasmodium berghei</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Plasmodium berghei</term><term>Saccharomyces cerevisiae</term><term>Toxoplasma</term><term>Trypanosoma brucei brucei</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Plasmodium berghei</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Plasmodium berghei</term><term>Saccharomyces cerevisiae</term><term>Toxoplasma</term><term>Trypanosoma brucei brucei</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Plasmodium berghei</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Plasmodium berghei</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Biological Evolution</term><term>Female</term><term>Gene Knockout Techniques</term><term>Genes, Essential</term><term>Genome, Protozoan</term><term>Host-Parasite Interactions</term><term>Metabolic Networks and Pathways</term><term>Mice</term><term>Mice, Inbred BALB C</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Femelle</term><term>Gènes essentiels</term><term>Génome de protozoaire</term><term>Interactions hôte-parasite</term><term>Souris</term><term>Souris de lignée BALB C</term><term>Techniques de knock-out de gènes</term><term>Voies et réseaux métaboliques</term><term>Évolution biologique</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en"><title>Summary</title><p>The genomes of malaria parasites contain many genes of unknown function. To assist drug development through the identification of essential genes and pathways, we have measured competitive growth rates in mice of 2,578 barcoded <italic>Plasmodium berghei</italic> knockout mutants, representing >50% of the genome, and created a phenotype database. At a single stage of its complex life cycle, <italic>P. berghei</italic> requires two-thirds of genes for optimal growth, the highest proportion reported from any organism and a probable consequence of functional optimization necessitated by genomic reductions during the evolution of parasitism. In contrast, extreme functional redundancy has evolved among expanded gene families operating at the parasite-host interface. The level of genetic redundancy in a single-celled organism may thus reflect the degree of environmental variation it experiences. In the case of <italic>Plasmodium</italic> parasites, this helps rationalize both the relative successes of drugs and the greater difficulty of making an effective vaccine.</p></div></front><back><div1 type="bibliography"><listBibl><biblStruct><analytic><author><name sortKey="Alexa, A" uniqKey="Alexa A">A. Alexa</name></author><author><name sortKey="Rahnenfuhrer, J" uniqKey="Rahnenfuhrer J">J. Rahnenführer</name></author><author><name sortKey="Lengauer, T" uniqKey="Lengauer T">T. Lengauer</name></author></analytic></biblStruct><biblStruct><analytic><author><name sortKey="Alsford, S" uniqKey="Alsford S">S. Alsford</name></author><author><name sortKey="Turner, D J" uniqKey="Turner D">D.J. Turner</name></author><author><name sortKey="Obado, S O" uniqKey="Obado S">S.O. Obado</name></author><author><name sortKey="Sanchez Flores, A" uniqKey="Sanchez Flores A">A. Sanchez-Flores</name></author><author><name sortKey="Glover, L" uniqKey="Glover L">L. 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DeRisi</name></author></analytic></biblStruct></listBibl></div1></back></TEI><affiliations><list><country><li>Australie</li><li>France</li><li>Royaume-Uni</li><li>États-Unis</li></country><region><li>Languedoc-Roussillon</li><li>Occitanie (région administrative)</li><li>Pennsylvanie</li><li>Victoria (État)</li></region><settlement><li>Melbourne</li><li>Montpellier</li></settlement><orgName><li>Université de Melbourne</li></orgName></list><tree><country name="Royaume-Uni"><noRegion><name sortKey="Bushell, Ellen" sort="Bushell, Ellen" uniqKey="Bushell E" first="Ellen" last="Bushell">Ellen Bushell</name></noRegion><name sortKey="Anar, Burcu" sort="Anar, Burcu" uniqKey="Anar B" first="Burcu" last="Anar">Burcu Anar</name><name sortKey="Billker, Oliver" sort="Billker, Oliver" uniqKey="Billker O" first="Oliver" last="Billker">Oliver Billker</name><name sortKey="Girling, Gareth" sort="Girling, Gareth" uniqKey="Girling G" first="Gareth" last="Girling">Gareth Girling</name><name sortKey="Gomes, Ana Rita" sort="Gomes, Ana Rita" uniqKey="Gomes A" first="Ana Rita" last="Gomes">Ana Rita Gomes</name><name sortKey="Herd, Colin" sort="Herd, Colin" uniqKey="Herd C" first="Colin" last="Herd">Colin Herd</name><name sortKey="Metcalf, Tom" sort="Metcalf, Tom" uniqKey="Metcalf T" first="Tom" last="Metcalf">Tom Metcalf</name><name sortKey="Modrzynska, Katarzyna" sort="Modrzynska, Katarzyna" uniqKey="Modrzynska K" first="Katarzyna" last="Modrzynska">Katarzyna Modrzynska</name><name sortKey="Parts, Leopold" sort="Parts, Leopold" uniqKey="Parts L" first="Leopold" last="Parts">Leopold Parts</name><name sortKey="Rayner, Julian C" sort="Rayner, Julian C" uniqKey="Rayner J" first="Julian C." last="Rayner">Julian C. Rayner</name><name sortKey="Rutledge, Gavin G" sort="Rutledge, Gavin G" uniqKey="Rutledge G" first="Gavin G." last="Rutledge">Gavin G. Rutledge</name><name sortKey="Sanderson, Theo" sort="Sanderson, Theo" uniqKey="Sanderson T" first="Theo" last="Sanderson">Theo Sanderson</name><name sortKey="Schwach, Frank" sort="Schwach, Frank" uniqKey="Schwach F" first="Frank" last="Schwach">Frank Schwach</name></country><country name="Australie"><noRegion><name sortKey="Martin, Rowena E" sort="Martin, Rowena E" uniqKey="Martin R" first="Rowena E." last="Martin">Rowena E. Martin</name></noRegion><name sortKey="Mcfadden, Geoffrey I" sort="Mcfadden, Geoffrey I" uniqKey="Mcfadden G" first="Geoffrey I." last="Mcfadden">Geoffrey I. Mcfadden</name></country><country name="États-Unis"><region name="Pennsylvanie"><name sortKey="Mather, Michael W" sort="Mather, Michael W" uniqKey="Mather M" first="Michael W." last="Mather">Michael W. Mather</name></region><name sortKey="Vaidya, Akhil B" sort="Vaidya, Akhil B" uniqKey="Vaidya A" first="Akhil B." last="Vaidya">Akhil B. Vaidya</name></country><country name="France"><region name="Occitanie (région administrative)"><name sortKey="Wengelnik, Kai" sort="Wengelnik, Kai" uniqKey="Wengelnik K" first="Kai" last="Wengelnik">Kai Wengelnik</name></region></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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