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The genome of the kinetoplastid parasite, Leishmania major.

ABSTRACT: Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes, of which 36% can be ascribed a putative function. These include genes involved in host-pathogen interactions, such as proteolytic enzymes, and extensive machinery for synthesis of complex surface glycoconjugates. The organization of protein-coding genes into long, strand-specific, polycistronic clusters and lack of general transcription factors in the L. major, Trypanosoma brucei, and Trypanosoma cruzi (Tritryp) genomes suggest that the mechanisms regulating RNA polymerase II-directed transcription are distinct from those operating in other eukaryotes, although the trypanosomatids appear capable of chromatin remodeling. Abundant RNA-binding proteins are encoded in the Tritryp genomes, consistent with active posttranscriptional regulation of gene expression.

SUBMITTER: Ivens AC

PROVIDER: S-EPMC1470643 | biostudies-literature | 2005 Jul

REPOSITORIES: biostudies-literature

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The genome of the kinetoplastid parasite, Leishmania major.

Ivens Alasdair C AC Peacock Christopher S CS Worthey Elizabeth A EA Murphy Lee L Aggarwal Gautam G Berriman Matthew M Sisk Ellen E Rajandream Marie-Adele MA Adlem Ellen E Aert Rita R Anupama Atashi A Apostolou Zina Z Attipoe Philip P Bason Nathalie N Bauser Christopher C Beck Alfred A Beverley Stephen M SM Bianchettin Gabriella G Borzym Katja K Bothe Gordana G Bruschi Carlo V CV Collins Matt M Cadag Eithon E Ciarloni Laura L Clayton Christine C Coulson Richard M R RM Cronin Ann A Cruz Angela K AK Davies Robert M RM De Gaudenzi Javier J Dobson Deborah E DE Duesterhoeft Andreas A Fazelina Gholam G Fosker Nigel N Frasch Alberto Carlos AC Fraser Audrey A Fuchs Monika M Gabel Claudia C Goble Arlette A Goffeau André A Harris David D Hertz-Fowler Christiane C Hilbert Helmut H Horn David D Huang Yiting Y Klages Sven S Knights Andrew A Kube Michael M Larke Natasha N Litvin Lyudmila L Lord Angela A Louie Tin T Marra Marco M Masuy David D Matthews Keith K Michaeli Shulamit S Mottram Jeremy C JC Müller-Auer Silke S Munden Heather H Nelson Siri S Norbertczak Halina H Oliver Karen K O'neil Susan S Pentony Martin M Pohl Thomas M TM Price Claire C Purnelle Bénédicte B Quail Michael A MA Rabbinowitsch Ester E Reinhardt Richard R Rieger Michael M Rinta Joel J Robben Johan J Robertson Laura L Ruiz Jeronimo C JC Rutter Simon S Saunders David D Schäfer Melanie M Schein Jacquie J Schwartz David C DC Seeger Kathy K Seyler Amber A Sharp Sarah S Shin Heesun H Sivam Dhileep D Squares Rob R Squares Steve S Tosato Valentina V Vogt Christy C Volckaert Guido G Wambutt Rolf R Warren Tim T Wedler Holger H Woodward John J Zhou Shiguo S Zimmermann Wolfgang W Smith Deborah F DF Blackwell Jenefer M JM Stuart Kenneth D KD Barrell Bart B Myler Peter J PJ

Science (New York, N.Y.) 20050701 5733

Leishmania species cause a spectrum of human diseases in tropical and subtropical regions of the world. We have sequenced the 36 chromosomes of the 32.8-megabase haploid genome of Leishmania major (Friedlin strain) and predict 911 RNA genes, 39 pseudogenes, and 8272 protein-coding genes, of which 36% can be ascribed a putative function. These include genes involved in host-pathogen interactions, such as proteolytic enzymes, and extensive machinery for synthesis of complex surface glycoconjugates ...[more]

PMID: 16020728

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Project description:Protein-coding genes in kinetoplastid protists are transcribed from polycistronic arrays, yielding RNA precursors which are processed to form mature transcripts bearing a 5M-bM-^@M-^Y spliced leader (SL) and 3M-bM-^@M-^Y poly(A) tract. Regions of transcription initiation and termination lack known eukaryotic promoter and terminator elements, and current data suggest that transcription is instead regulated predominantly through epigenetic mechanisms. Several epigenetic marks, including histone modifications, histone variants, and an atypical DNA modification known as base J have been localized to regions of transcription initiation or termination in Trypanosoma brucei, Trypanosoma cruzi, and/or Leishmania major. Despite this conservation, the phenotypes of base J mutants vary significantly across trypanosomatids, suggesting that the specific epigenetic networks governing transcription initiation and termination have diverged significantly during evolution. In this light, we sought to characterize and compare the roles of the histone variants H2A.Z, H2B.V, and H3.V in L. major. As in T. brucei, the histone variants H2A.Z and H2B.V were shown to be essential in L. major using a powerful quantitative plasmid segregation-based test. In contrast and again similar to T. brucei, H3.V is not essential in Leishmania as H3.V-null lines grew normally, resembled WT, and remained infectious. Using SL-primed RNA-seq, we found that H3.V-null parasites have steady-state transcript levels comparable to WT parasites and display no defects in the efficiency of transcription termination at convergent strand switch regions (SSRs). Our results show a conservation of histone variant phenotypes between L. major and T. brucei, in contrast to the phenotypes associated with the epigenetic DNA base J modification. Total RNA from Four LmjF samples were analyzed using RNA-Seq. One of them is wildtype parasites, one is single knockout for H3V gene and two independent double knockouts for H3V gene.

Dataset Information

The genome of the kinetoplastid parasite, Leishmania major.

Publications

The genome of the kinetoplastid parasite, Leishmania major.

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