Promoter identification in bacterial genomes: Role of DNA
structure vs sequence
Manju Bansal* and Vetriselvi Rangannan
Molecular Biophysics Unit, Indian Institute of Science, Bangalore – 560 012, India.
Several algorithms for the identification of promoters and transcription factor binding
sites in DNA sequence have been proposed, generally based on patterns (sequence motifs)
in genome sequences. One common approach has been to discriminate promoter from
non-promoter or intergenic from coding regions, based on hexanucleotide analysis.
Relative frequencies of transcription factor binding sites in different regions of DNA are
also being used to detect promoters. In general, under conditions where these sequence
based promoter prediction algorithms are able to provide acceptable results, in terms of
identification of known promoters (true positives), then the number of wrongly predicted
promoters (false positives) is very high. It has also been now accepted that DNA
sequence-dependent stability and structure is equally important for transcriptional
regulation. The differences in these properties, particularly in the stability of DNA,
provide additional and improved criteria for identifying promoter regions from nonpromoter regions, than sequences alone. Based on the analysis of differences in stability
between neighboring regions (upstream and downstream regions), a promoter prediction
algorithm had been developed in our laboratory to identify prokaryotic promoter regions
and tested on known E. coli and B. subtilis promoter sequences and subsequently applied
to analyze whole genome sequences. A high level of sensitivity is achieved, when the
free energy differences between the known E. coli promoter sequences and entire E. coli
genome are used as thresholds to search for promoters in the E. coli genome sequence.
The tetramer and hexamer sequences in the promoter regions have also been examined to
look for a correlation with stability and other structural properties, such as curvature and
bendability in promoter regions.