Abstract

Leishmania parasites cause a broad spectrum of clinical disease. Here we report the sequencing of the genomes of two species of Leishmania: Leishmania infantum and Leishmania braziliensis. The comparison of these sequences with the published genome of Leishmania major reveals marked conservation of synteny and identifies only 200 genes with a differential distribution between the three species. L. braziliensis, contrary to Leishmania species examined so far, possesses components of a putative RNA-mediated interference pathway, telomere-associated transposable elements and spliced leader–associated SLACS retrotransposons. We show that pseudogene formation and gene loss are the principal forces shaping the different genomes. Genes that are differentially distributed between the species encode proteins implicated in host-pathogen interactions and parasite survival in the macrophage.

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Acknowledgements

We acknowledge the support of the Wellcome Trust Sanger Institute core sequencing and informatics groups. We thank N. Goldman (European Bioinformatics Institute) for advice on the evolutionary analysis, C. Hertz-Fowler for help in constructing the figures, J. Shaw for his help in selecting the strain for the L. braziliensis genome sequencing project and D. Harper for quality scores on the sequencing projects. This study was funded by the Wellcome Trust through its support of the Pathogen Sequencing Unit at the Wellcome Trust Sanger Institute. L.O.B. and J.C.R. were recipients of Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) fellowships. D.P.D. was supported by a postgraduate studentship from the Biotechnology and Biological Sciences Research Council. J.C.R. received financial support from the UNICEF/UNDP/WORLD BANK/WHO Special Programme for Research and Training in Tropical Diseases (TDR).

Author information

Affiliations

  1. Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.

    • Christopher S Peacock
    • , Kathy Seeger
    • , David Harris
    • , Lee Murphy
    • , Michael A Quail
    • , Nick Peters
    • , Ellen Adlem
    • , Adrian Tivey
    • , Martin Aslett
    • , Arnaud Kerhornou
    • , Alasdair Ivens
    • , Audrey Fraser
    • , Marie-Adele Rajandream
    • , Tim Carver
    • , Halina Norbertczak
    • , Tracey Chillingworth
    • , Zahra Hance
    • , Kay Jagels
    • , Sharon Moule
    • , Doug Ormond
    • , Simon Rutter
    • , Rob Squares
    • , Sally Whitehead
    • , Ester Rabbinowitsch
    • , Claire Arrowsmith
    • , Brian White
    • , Scott Thurston
    • , Daniel Jeffares
    • , Barclay Barrell
    •  & Matthew Berriman
  2. Departmento de Biologia Celular e Molecular e Bioagentes Patogênicos, Faculdade de Medicina, de Ribeirão Preto, Universidade de São Paulo, Avenida Bandeirantes 3900, CEP 14049-900 Ribeirão Preto, São Paulo, Brazil.

    • Jeronimo C Ruiz
    • , Loislene O Brito
    • , Luiz R O Tosi
    •  & Angela K Cruz
  3. Laboratoire de Génomique Fonctionnelle des Trypanosomatides, Universitité Victoir Segalen Bordeaux II, UMR-5162 CNRS, 33076 Bordeaux Cedex, France.

    • Frédéric Bringaud
  4. Immunology and Infection Unit, Department of Biology, University of York, York YO10 5YW, UK.

    • Sandra L Baldauf
    • , Adam Faulconbridge
    • , Daniel P Depledge
    • , Samuel O Oyola
    •  & Deborah F Smith
  5. Wellcome Centre for Molecular Parasitology and Division of Infection & Immunity, Glasgow Biomedical Research Centre, University of Glasgow, 120 University Place, Glasgow G12 8TN, UK.

    • James D Hilley
    •  & Jeremy C Mottram

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Contributions

C.S.P., M.B., D.F.S., A.K.C., J.C.M. and B.B. worked on all aspects of work, contributed to the design of the project and wrote the article. C.S.P. and J.C.R. annotated the genomes; K.S., D.H. and L.M. carried out the assembly and finishing of the genomes; A.F., T.C., Z.H., K.J., S.M., D.O., S.R., R.S., S.W., C.A. and B.W. sequenced the genomes and M.A.Q., H.N., E.R. and S.T. made the clone libraries. N.P., E.A., A.T., M.A., A.K., A.I., M.-A.R. and T.C. wrote and developed software for annotation and comparative analysis of the three genome sequences. F.B. worked on identifying the transposable elements, and S.L.B. and A.F. worked on the phylogenetic analysis of CFA synthase. A.K.C., L.O.B. and L.R.O.T. elucidated the RNAi pathway. D.J. performed the evolutionary analysis, and D.P.D. analyzed the amino acid repeats. D.F.S., J.C.M., S.O.O. and J.D.H. worked on some of the species-specific genes.

Competing interests

The authors declare no competing financial interests.

Corresponding authors

Correspondence to Christopher S Peacock or Matthew Berriman.

Supplementary information

PDF files

  1. 1.

    Supplementary Fig. 1

    The predicted structure of the telomere-associated transposable elements (TATEs) found in L. braziliensis.

  2. 2.

    Supplementary Fig. 2

    RNAi machinery in Leishmania species.

  3. 3.

    Supplementary Fig. 3

    The phylogenetic tree for cyclopropane fatty acyl phosholipid synthase (CFAS).

  4. 4.

    Supplementary Table 1

    Summary of motifs reported in RNAi proteins.

  5. 5.

    Supplementary Table 2

    Leishmania loci with species-specific differences and conserved pseudogenes.

  6. 6.

    Supplementary Table 3

    dN/dS analysis of Leishmania genes annotated with Gene Ontology Biological Process terms.

  7. 7.

    Supplementary Table 4

    Genes predicted to have evolved at different rates between the three species of Leishmania.

  8. 8.

    Supplementary Table 5

    Gene Ontology groups that are overrepresented in the 924 genes that show significant divergence within orthologous groups.

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DOI

https://doi.org/10.1038/ng2053

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