Genome-wide mutational biases fuel transcriptional diversity in the Mycobacterium tuberculosis complex
Por:
Chiner-Oms Á, Berney M, Boinett C, González-Candelas F, Young DB, Gagneux S, Jacobs WR, Parkhill J, Cortes T and Comas I
Publicada:
5 sep 2019
Ahead of Print:
5 sep 2019
Resumen:
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.
Filiaciones:
:
Unidad Mixta "Infección y Salud Pública" FISABIO-CSISP/Universidad de Valencia, Instituto de Biología Integrativa de Sistemas-I2SysBio, Valencia, Spain
Instituto de Biomedicina de Valencia, IBV-CSIC, Valencia, Spain
Berney M:
Department of Microbiology and Immunology and Department of Molecular Genetics, Albert Einstein College of Medicine, New York, USA
Boinett C:
Sanger Institute, Wellcome Genome Campus, Hinxton, Cambridge, UK
Hospital for Tropical Diseases, Wellcome Trust Major Overseas Programme, Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam
:
Unidad Mixta "Infección y Salud Pública" FISABIO-CSISP/Universidad de Valencia, Instituto de Biología Integrativa de Sistemas-I2SysBio, Valencia, Spain
CIBER en Epidemiología y Salud Pública, Valencia, Spain
Young DB:
The Francis Crick Institute, London, UK
Gagneux S:
Swiss Tropical and Public Health Institute, Basel, Switzerland
University of Basel, Basel, Switzerland
Jacobs WR:
Department of Microbiology and Immunology and Department of Molecular Genetics, Albert Einstein College of Medicine, New York, USA
Parkhill J:
Department of Veterinary Medicine, University of Cambridge, Mandingley Road, Cambiddge, CB3 OES, UK
Cortes T:
Department of Infection Biology, Faculty of Infectious and Tropical Diseases, London School of Hygiene and Tropical Medicine, London, UK.
:
Instituto de Biomedicina de Valencia, IBV-CSIC, Valencia, Spain.
CIBER en Epidemiología y Salud Pública, Valencia, Spain.
Green Published, gold, Green Accepted
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