The evolutionary landscape of the Mycobacterium tuberculosis genome

Mycobacterium tuberculosis is one of the most deadly human pathogens. The major mechanism for the adaptations of M. tuberculosis is nucleotide substitution. Previous studies have relied on the nonsynonymous-to-synonymous substitution rate (dN/dS) ratio as a measurement of selective constraint based...

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Bibliographic Details
Published in:Gene 2013-04, Vol.518 (1), p.187-193
Main Authors: Wang, Tai-Chun, Chen, Feng-Chi
Format: Article
Language:English
Subjects:
Base Sequence
Biological Evolution
Conserved Sequence
DNA, Intergenic
Evolution, Molecular
genes
Genome, Bacterial
humans
intergenic DNA
Mutation
Mycobacterium - genetics
Mycobacterium tuberculosis
Mycobacterium tuberculosis - genetics
Neutral substitution rate
Nonsynonymous substitution
pathogens
Selection pressure
Selection, Genetic
Synonymous substitution
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Summary:Mycobacterium tuberculosis is one of the most deadly human pathogens. The major mechanism for the adaptations of M. tuberculosis is nucleotide substitution. Previous studies have relied on the nonsynonymous-to-synonymous substitution rate (dN/dS) ratio as a measurement of selective constraint based on the assumed selective neutrality of synonymous substitutions. However, this assumption has been shown to be untrue in many cases. In this study, we used the substitution rate in intergenic regions (di) of the M. tuberculosis genome as the neutral reference, and conducted a genome-wide profiling for di, dS, and the rate of insertions/deletions (indel rate) as compared with the genome of M. canettii using a 50kb sliding window. We demonstrate significant variations in all of the three evolutionary measurements across the M. tuberculosis genome, even for regions in close vicinity. Furthermore, we identified a total of 233 genes with their dS deviating significantly from di within the same window. Interestingly, dS also varies significantly in some of the windows, indicating drastic changes in mutation rate and/or selection pressure within relatively short distances in the M. tuberculosis genome. Importantly, our results indicate that selection on synonymous substitutions is common in the M. tuberculosis genome. Therefore, the dN/dS ratio test must be applied carefully for measuring selection pressure on M. tuberculosis genes. ► We examined the evolutionary rates of the Mycobacterium tuberculosis genomes. ► Substitution and insertion/deletion rates vary significantly across the genomes. ► Many M. tuberculosis genes have dS deviate significantly from neutral rate (di). ► dN/di should be used instead of dN/dS for measuring selection pressure.
ISSN:0378-1119
1879-0038
DOI:10.1016/j.gene.2012.11.033