Gene expression in Leishmania is regulated predominantly by gene dosage

Iantorno, S. A. et al. (2017) Gene expression in Leishmania is regulated predominantly by gene dosage. mBio, 8(5), e01393-17. (doi: 10.1128/mBio.01393-17) (PMID:28900023) (PMCID:PMC5596349)

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Leishmania tropica, a unicellular eukaryotic parasite present in North and East Africa, the Middle East, and the Indian subcontinent, has been linked to large outbreaks of cutaneous leishmaniasis in displaced populations in Iraq, Jordan, and Syria. Here, we report the genome sequence of this pathogen and 7,863 identified protein-coding genes, and we show that the majority of clinical isolates possess high levels of allelic diversity, genetic admixture, heterozygosity, and extensive aneuploidy. By utilizing paired genome-wide high-throughput DNA sequencing (DNA-seq) with RNA-seq, we found that gene dosage, at the level of individual genes or chromosomal “somy” (a general term covering disomy, trisomy, tetrasomy, etc.), accounted for greater than 85% of total gene expression variation in genes with a 2-fold or greater change in expression. High gene copy number variation (CNV) among membrane-bound transporters, a class of proteins previously implicated in drug resistance, was found for the most highly differentially expressed genes. Our results suggest that gene dosage is an adaptive trait that confers phenotypic plasticity among natural Leishmania populations by rapid down- or upregulation of transporter proteins to limit the effects of environmental stresses, such as drug selection.

Item Type:Articles
Glasgow Author(s) Enlighten ID:Cotton, Professor James and Berriman, Professor Matt
Authors: Iantorno, S. A., Durrant, C., Khan, A., Sanders, M. J., Beverley, S. M., Warren, W. C., Berriman, M., Sacks, D. L., Cotton, J. A., Grigg, M. E., Weiss, L. M., Ouellette, M., and Myler, P.
College/School:College of Medical Veterinary and Life Sciences > School of Biodiversity, One Health & Veterinary Medicine
College of Medical Veterinary and Life Sciences > School of Infection & Immunity
Journal Name:mBio
Publisher:American Society for Microbiology
ISSN (Online):2150-7511
Published Online:12 September 2017

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