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

Álvaro Chiner-Oms, Michael Berney, Christine Boinett, Fernando González-Candelas, Douglas B. Young, Sebastien Gagneux, William R. Jacobs, Julian Parkhill, Teresa Cortes, Iñaki Comas

Research output: Contribution to journalArticle

1 Scopus citations

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.

Original languageEnglish (US)
Article number3994
JournalNature communications
Volume10
Issue number1
DOIs
StatePublished - Dec 1 2019

ASJC Scopus subject areas

  • Chemistry(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Physics and Astronomy(all)

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    Chiner-Oms, Á., Berney, M., Boinett, C., González-Candelas, F., Young, D. B., Gagneux, S., Jacobs, W. R., Parkhill, J., Cortes, T., & Comas, I. (2019). Genome-wide mutational biases fuel transcriptional diversity in the Mycobacterium tuberculosis complex. Nature communications, 10(1), [3994]. https://doi.org/10.1038/s41467-019-11948-6