Genome-wide analysis of the intrinsic terminators of transcription across the genus Mycobacterium.

Termination of transcription in eubacteria is achieved by a region of the nascent transcript. In Escherichia coli, this intrinsic terminator consists of a hairpin followed by a U-stretch. Absence of the typical terminators in several genes of Mycobacterium tuberculosis led us to develop an accurate and efficient algorithm to identify putative terminators in all sequenced microbial genomes. In addition to the typical Escherichia coli type of terminators, several variant terminator structures were predicted by the algorithm and their existence was experimentally verified. We have now analysed 17 Mycobacterium genomes to obtain a comprehensive picture of the transcription terminators in mycobacteria. Our results show that the terminators that lack a U-trail, variant from the typical E. coli intrinsic terminators, are overwhelmingly predominant in all members of the genus. Most terminator structures are concentrated within 50 base pairs downstream of the stop codon. A large number of these terminators occur at the end of experimentally verified or predicted transcription units. We have observed inter-species variations in ΔG and positioning of the terminators downstream of specific genes amongst closely related mycobacterial species suggesting differences in gene expression. The analysis would be useful in furthering our understanding of genome organization and gene expression in mycobacteria, in addition to the improvement in the annotation of the new genomes.