Relaxed selection drives a noisy noncoding transcriptome in members of the Mycobacterium tuberculosis complex.
Bottom Line: A small number of studies have compared the primary transcriptomes of different bacterial species, but few have compared closely related species with clearly divergent evolutionary histories.We show that a species population history is reflected in its transcriptome and posit relaxed selection as the main driver of an abundance of canonical -10 promoter sites in M. bovis relative to M. marinum.Finally, through comparison of M. bovis and M. tuberculosis, we illustrate that single nucleotide polymorphism (SNP)-driven promoter differences likely underpin many of the transcriptional differences between M. tuberculosis complex lineages.
Affiliation: Wellcome Trust Cell Biology Centre, The University of Edinburgh, Edinburgh, United Kingdom.Show MeSH
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Mentions: To explore the extent to which a genome’s density of −10 boxes correlates with promoter occupancy, we determined the number of consensus −10 sites in M. bovis being filled by at least 10 TEX+ reads, a number which is lower than the cutoff of 20 reads used for actual TSS calls, while maintaining a minimum TEX+/TEX− ratio of at least 2:1. Applying this relaxed criterion, designed to mimic the effect of increased sequencing depth, resulted in 7,770 (50%) of the total 15,569 consensus −10 box sites being occupied at the fully mapped library size of ~6.6 million TEX+ reads (excluding rRNA). We also determined the degree to which −10 site occupancy by the accumulation of TEX+ reads contributes to TSS identification by mapping the relationship across different library sizes (Fig. 3A). The rate at which −10 boxes were found to become occupied mirrors almost exactly the call rate for TSSs, indicating that the identified TSSs and their distributions are largely functions of the presence of an appropriate initiation site combined with an appropriate sequencing depth. In contrast, equivalent numbers of randomly selected genomic positions show a significantly lower level of occupancy at each depth (P <2.2e-16, Pearson’s chi-square test).
Affiliation: Wellcome Trust Cell Biology Centre, The University of Edinburgh, Edinburgh, United Kingdom.