Chromosome and gene copy number variation allow major structural change between species and strains of Leishmania
- Matthew B. Rogers1,2,9,
- James D. Hilley3,9,
- Nicholas J. Dickens3,9,
- Jon Wilkes3,
- Paul A. Bates4,
- Daniel P. Depledge1,2,
- David Harris1,
- Yerim Her2,
- Pawel Herzyk5,
- Hideo Imamura1,6,
- Thomas D. Otto1,
- Mandy Sanders1,
- Kathy Seeger1,
- Jean-Claude Dujardin6,7,
- Matthew Berriman1,
- Deborah F. Smith2,
- Christiane Hertz-Fowler1,8,10 and
- Jeremy C. Mottram3,10
- 1Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Cambridge CB10 1SA, United Kingdom;
- 2Department of Biology, University of York, Heslington, York YO10 5DD, United Kingdom;
- 3Wellcome Trust Centre for Molecular Parasitology, Institute of Infection, Immunity and Inflammation, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, United Kingdom;
- 4Division of Biomedical and Life Sciences, School of Health and Medicine, Lancaster University, Lancaster LA1 4YQ, United Kingdom;
- 5Institute of Molecular, Cell and Systems Biology, College of Medical, Veterinary and Life Sciences, University of Glasgow, Glasgow G12 8TA, United Kingdom;
- 6Unit of Molecular Parasitology, Department of Parasitology, Institute of Tropical Medicine, B-2000 Antwerp, Belgium;
- 7Department of Biomedical Sciences, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, B-2020 Antwerp, Belgium
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↵9 These authors contributed equally to this work.
Abstract
Leishmania parasites cause a spectrum of clinical pathology in humans ranging from disfiguring cutaneous lesions to fatal visceral leishmaniasis. We have generated a reference genome for Leishmania mexicana and refined the reference genomes for Leishmania major, Leishmania infantum, and Leishmania braziliensis. This has allowed the identification of a remarkably low number of genes or paralog groups (2, 14, 19, and 67, respectively) unique to one species. These were found to be conserved in additional isolates of the same species. We have predicted allelic variation and find that in these isolates, L. major and L. infantum have a surprisingly low number of predicted heterozygous SNPs compared with L. braziliensis and L. mexicana. We used short read coverage to infer ploidy and gene copy numbers, identifying large copy number variations between species, with 200 tandem gene arrays in L. major and 132 in L. mexicana. Chromosome copy number also varied significantly between species, with nine supernumerary chromosomes in L. infantum, four in L. mexicana, two in L. braziliensis, and one in L. major. A significant bias against gene arrays on supernumerary chromosomes was shown to exist, indicating that duplication events occur more frequently on disomic chromosomes. Taken together, our data demonstrate that there is little variation in unique gene content across Leishmania species, but large-scale genetic heterogeneity can result through gene amplification on disomic chromosomes and variation in chromosome number. Increased gene copy number due to chromosome amplification may contribute to alterations in gene expression in response to environmental conditions in the host, providing a genetic basis for disease tropism.
Footnotes
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↵10 Corresponding authors.
E-mail C.Hertz-Fowler{at}liverpool.ac.uk.
E-mail jeremy.mottram{at}glasgow.ac.uk.
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[Supplemental material is available for this article.]
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Article published online before print. Article, supplemental material, and publication date are at http://www.genome.org/cgi/doi/10.1101/gr.122945.111. Freely available online through the Genome Research Open Access option.
- Received March 22, 2011.
- Accepted August 23, 2011.
- Copyright © 2011 by Cold Spring Harbor Laboratory Press
Freely available online through the Genome Research Open Access option.