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Transition bias influences the evolution of antibiotic resistance in Mycobacterium tuberculosis
- Source :
- PLoS Biology, Vol 17, Iss 5, p e3000265 (2019), PLoS Biology, 17 (5), PLoS Biology
- Publication Year :
- 2019
- Publisher :
- Public Library of Science (PLoS), 2019.
-
Abstract
- Transition bias, an overabundance of transitions relative to transversions, has been widely reported among studies of the rates and spectra of spontaneous mutations. However, demonstrating the role of transition bias in adaptive evolution remains challenging. In particular, it is unclear whether such biases direct the evolution of bacterial pathogens adapting to treatment. We addressed this challenge by analyzing adaptive antibiotic-resistance mutations in the major human pathogen Mycobacterium tuberculosis (MTB). We found strong evidence for transition bias in two independently curated data sets comprising 152 and 208 antibiotic-resistance mutations. This was true at the level of mutational paths (distinct adaptive DNA sequence changes) and events (individual instances of the adaptive DNA sequence changes) and across different genes and gene promoters conferring resistance to a diversity of antibiotics. It was also true for mutations that do not code for amino acid changes (in gene promoters and the 16S ribosomal RNA gene rrs) and for mutations that are synonymous to each other and are therefore likely to have similar fitness effects, suggesting that transition bias can be caused by a bias in mutation supply. These results point to a central role for transition bias in determining which mutations drive adaptive antibiotic resistance evolution in a key pathogen.<br />Some types of mutations occur more frequently than expected. This study shows that such bias —an excess of transitions over transversions—influences the evolution of antibiotic resistance in a key global pathogen, Mycobacterium tuberculosis.
- Subjects :
- Human pathogen
medicine.disease_cause
Database and Informatics Methods
0302 clinical medicine
Mathematical and Statistical Techniques
Short Reports
Antibiotics
Medicine and Health Sciences
Biology (General)
Phylogeny
Genetics
0303 health sciences
Mutation
Transition (genetics)
biology
Antimicrobials
Mathematical Models
Nucleotides
Drugs
Genomics
Genomic Databases
3. Good health
Actinobacteria
QH301-705.5
Research and Analysis Methods
Microbiology
DNA sequencing
Mycobacterium tuberculosis
Evolution, Molecular
03 medical and health sciences
Antibiotic resistance
Bacterial Proteins
Microbial Control
Drug Resistance, Bacterial
medicine
Point Mutation
Amino Acid Sequence
Gene
030304 developmental biology
Pharmacology
Bacteria
Organisms
Biology and Life Sciences
Computational Biology
Promoter
biology.organism_classification
Genome Analysis
Biological Databases
Antibiotic Resistance
Mutation Databases
Antimicrobial Resistance
030217 neurology & neurosurgery
Subjects
Details
- Language :
- English
- ISSN :
- 15457885 and 15449173
- Volume :
- 17
- Issue :
- 5
- Database :
- OpenAIRE
- Journal :
- PLoS Biology
- Accession number :
- edsair.doi.dedup.....4a5d06eb32e330c64f8e834e171309eb