Gene Expression in Leishmania Is Regulated Predominantly by Gene Dosage
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 pathoge...
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American Society for Microbiology
2017-09-01
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doaj-1f3cf271e02b416a972f95ae3bd183f62021-07-02T02:07:08ZengAmerican Society for MicrobiologymBio2150-75112017-09-0185e01393-1710.1128/mBio.01393-17Gene Expression in Leishmania Is Regulated Predominantly by Gene DosageStefano A. IantornoCaroline DurrantAsis KhanMandy J. SandersStephen M. BeverleyWesley C. WarrenMatthew BerrimanDavid L. SacksJames A. CottonMichael E. GriggLouis M. WeissLeishmania 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.http://mbio.asm.org/cgi/content/full/8/5/e01393-17 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Stefano A. Iantorno Caroline Durrant Asis Khan Mandy J. Sanders Stephen M. Beverley Wesley C. Warren Matthew Berriman David L. Sacks James A. Cotton Michael E. Grigg Louis M. Weiss |
spellingShingle |
Stefano A. Iantorno Caroline Durrant Asis Khan Mandy J. Sanders Stephen M. Beverley Wesley C. Warren Matthew Berriman David L. Sacks James A. Cotton Michael E. Grigg Louis M. Weiss Gene Expression in Leishmania Is Regulated Predominantly by Gene Dosage mBio |
author_facet |
Stefano A. Iantorno Caroline Durrant Asis Khan Mandy J. Sanders Stephen M. Beverley Wesley C. Warren Matthew Berriman David L. Sacks James A. Cotton Michael E. Grigg Louis M. Weiss |
author_sort |
Stefano A. Iantorno |
title |
Gene Expression in Leishmania Is Regulated Predominantly by Gene Dosage |
title_short |
Gene Expression in Leishmania Is Regulated Predominantly by Gene Dosage |
title_full |
Gene Expression in Leishmania Is Regulated Predominantly by Gene Dosage |
title_fullStr |
Gene Expression in Leishmania Is Regulated Predominantly by Gene Dosage |
title_full_unstemmed |
Gene Expression in Leishmania Is Regulated Predominantly by Gene Dosage |
title_sort |
gene expression in leishmania is regulated predominantly by gene dosage |
publisher |
American Society for Microbiology |
series |
mBio |
issn |
2150-7511 |
publishDate |
2017-09-01 |
description |
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. |
url |
http://mbio.asm.org/cgi/content/full/8/5/e01393-17 |
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