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Comparative life cycle transcriptomics revises Leishmania mexicana genome annotation and links a chromosome duplication with parasitism of vertebrates

Abstract:
Leishmania spp. are protozoan parasites that have two principal life cycle stages: the motile promastigote forms that live in the alimentary tract of the sandfly and the amastigote forms, which are adapted to survive and replicate in the harsh conditions of the phagolysosome of mammalian macrophages. Here, we used Illumina sequencing of poly-A selected RNA to characterise and compare the transcriptomes of L. mexicana promastigotes, axenic amastigotes and intracellular amastigotes. These data allowed the production of the first transcriptome evidence-based annotation of gene models for this species, including genome-wide mapping of trans-splice sites and poly-A addition sites. The revised genome annotation encompassed 9,169 protein-coding genes including 936 novel genes as well as modifications to previously existing gene models. Comparative analysis of gene expression across promastigote and amastigote forms revealed that 3,832 genes are differentially expressed between promastigotes and intracellular amastigotes. A large proportion of genes that were downregulated during differentiation to amastigotes were associated with the function of the motile flagellum. In contrast, those genes that were upregulated included cell surface proteins, transporters, peptidases and many uncharacterized genes, including 293 of the 936 novel genes. Genome-wide distribution analysis of the differentially expressed genes revealed that the tetraploid chromosome 30 is highly enriched for genes that were upregulated in amastigotes, providing the first evidence of a link between this whole chromosome duplication event and adaptation to the vertebrate host in this group. Peptide evidence for 42 proteins encoded by novel transcripts supports the idea of an as yet uncharacterised set of small proteins in Leishmania spp. with possible implications for host-pathogen interactions.
Publication status:
Published
Peer review status:
Peer reviewed

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Publisher copy:
10.1371/journal.ppat.1005186

Authors

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Institution:
University of Oxford
Division:
MSD
Department:
Pathology Dunn School
Role:
Author
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Institution:
University of Oxford
Division:
MPLS
Department:
Plant Sciences
Role:
Author
More by this author
Institution:
University of Oxford
Division:
MSD
Department:
Pathology Dunn School
Role:
Author


More from this funder
Funding agency for:
Gluenz, E
Grant:
Royal Society University Research Fellow
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Funding agency for:
Kelly, S
Grant:
Leverhulme Trust Early Career Fellowship
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Funding agency for:
Kelly, S
Grant:
Leverhulme Trust Early Career Fellowship
More from this funder
Funding agency for:
Fiebig, M
Grant:
092870/Z/10/Z


Publisher:
Public Library of Science
Journal:
PLoS pathogens More from this journal
Volume:
11
Issue:
10
Pages:
e1005186
Publication date:
2015-10-01
DOI:
EISSN:
1553-7374
ISSN:
1553-7366


Language:
English
Pubs id:
pubs:579529
UUID:
uuid:123e31b6-4af9-4b7c-b9ea-3af829827ff7
Local pid:
pubs:579529
Source identifiers:
579529
Deposit date:
2016-01-14
ARK identifier:

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