ArticleGenome biology and evolution2013
Mapping of genotype-phenotype diversity among clinical isolates of mycobacterium tuberculosis by sequence-based transcriptional profiling.
Article in Genome biology and evolution, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
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Who cites it
42 citing papers in PubMed, 73 citations in OpenAlex.
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- Molecular epidemiology of bovine tuberculosis in Northern Ghana identifies several uncharacterized bovine spoligotypes and suggests possible zoonotic transmission.PLoS neglected tropical diseases · 2022Article
- Dual RNA Sequencing ofInternational journal of molecular sciences · 2022Article
- Contribution and Future of High-Throughput Transcriptomics in Battling Tuberculosis.Frontiers in microbiology · 2022Review
- Atypical Genetic Basis of Pyrazinamide Resistance in Monoresistant Mycobacterium tuberculosis.Antimicrobial agents and chemotherapy · 2021Article
- Metabolic Versatility ofMetabolites · 2021Review
- A Low-Prevalence Single-Nucleotide Polymorphism in the Sensor Kinase PhoR inFrontiers in microbiology · 2021Article
- Identification andHeliyon · 2020Article
- Genome-wide mutational biases fuel transcriptional diversity in the Mycobacterium tuberculosis complex.Nature communications · 2019Article
- Impact of Species Diversity on the Design of RNA-Based Diagnostics for Antibiotic Resistance inAntimicrobial agents and chemotherapy · 2019Article
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- Carbon metabolism modulates the efficacy of drugs targeting the cytochrome bcScientific reports · 2019Article
- An integrated whole genome analysis of Mycobacterium tuberculosis reveals insights into relationship between its genome, transcriptome and methylome.Scientific reports · 2019Article
- Reference set of Mycobacterium tuberculosis clinical strains: A tool for research and product development.PloS one · 2019Article
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Authors and funding
6 authors at 3 institutions in 3 countries.
Funding
Abstract
Genome sequencing has identified an extensive repertoire of single nucleotide polymorphisms among clinical isolates of Mycobacterium tuberculosis, but the extent to which these differences influence phenotypic properties of the bacteria remains to be elucidated. To determine whether these polymorphisms give rise to phenotypic diversity, we have integrated genome data sets with RNA sequencing to assess their impact on the comparative transcriptome profiles of strains belonging to M. tuberculosis Lineages 1 and 2. We observed clear correlations between genotype and transcriptional phenotype. These arose by three mechanisms. First, lineage-specific changes in amino acid sequence of transcriptional regulators were associated with alterations in their ability to control gene expression. Second, changes in nucleotide sequence were associated with alteration of promoter activity and generation of novel transcriptional start sites in intergenic regions and within coding sequences. We show that in some cases this mechanism is expected to generate functionally active truncated proteins involved in innate immune recognition. Finally, genes showing lineage-specific patterns of differential expression not linked directly to primary mutations were characterized by a striking overrepresentation of toxin-antitoxin pairs. Taken together, these findings advance our understanding of mycobacterial evolution, contribute to a systems level understanding of this important human pathogen, and more broadly demonstrate the application of state-of-the-art techniques to provide novel insight into mechanisms by which intergenic and silent mutations contribute to diversity.
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