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Genome-wide mutational biases fuel transcriptional diversity in the Mycobacterium tuberculosis complex

Chiner-Oms, Álvaro and Berney, Michael and Boinett, Christine and González-Candelas, Fernando and Young, Douglas B. and Gagneux, Sebastien and Jacobs, William R. and Parkhill, Julian and Cortes, Teresa and Comas, Iñaki. (2019) Genome-wide mutational biases fuel transcriptional diversity in the Mycobacterium tuberculosis complex. Nature Communications, 10. p. 3994.

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Abstract

The Mycobacterium tuberculosis complex (MTBC) members display different host-specificities and virulence phenotypes. Here, we have performed a comprehensive RNAseq and methylome analysis of the main clades of the MTBC and discovered unique transcriptional profiles. The majority of genes differentially expressed between the clades encode proteins involved in host interaction and metabolic functions. A significant fraction of changes in gene expression can be explained by positive selection on single mutations that either create or disrupt transcriptional start sites (TSS). Furthermore, we show that clinical strains have different methyltransferases inactivated and thus different methylation patterns. Under the tested conditions, differential methylation has a minor direct role on transcriptomic differences between strains. However, disruption of a methyltransferase in one clinical strain revealed important expression differences suggesting indirect mechanisms of expression regulation. Our study demonstrates that variation in transcriptional profiles are mainly due to TSS mutations and have likely evolved due to differences in host characteristics.
Faculties and Departments:09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH)
09 Associated Institutions > Swiss Tropical and Public Health Institute (Swiss TPH) > Department of Medical Parasitology and Infection Biology (MPI) > Tuberculosis Research (Gagneux)
UniBasel Contributors:Gagneux, Sebastien
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Nature Publishing Group
e-ISSN:2041-1723
Note:Publication type according to Uni Basel Research Database: Journal article
Language:English
Identification Number:
Last Modified:18 Sep 2019 06:59
Deposited On:18 Sep 2019 06:59

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