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

Published version
Peer-reviewed

Type

Article

Change log

Authors

Chiner-Oms, Álvaro  ORCID logo  https://orcid.org/0000-0002-0463-0101
Boinett, Christine 
González-Candelas, Fernando  ORCID logo  https://orcid.org/0000-0002-0879-5798
Young, Douglas B 

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.

Description

Keywords

DNA Methylation, Evolution, Molecular, Gene Expression Regulation, Bacterial, Genetic Variation, Genome, Bacterial, Humans, Methyltransferases, Mutation, Mycobacterium tuberculosis, Phenotype, Phylogeny, Transcriptome, Tuberculosis, Virulence

Journal Title

Nat Commun

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

10

Publisher

Springer Science and Business Media LLC