Prediction of transcription regulatory sites in Archaea by a comparative genomic approach

Intragenomic and intergenomic comparisons of upstream nucleotide sequences of archaeal genes were performed with the goal of predicting transcription regulatory sites (operators) and identifying likely regulons, Learning sets for the detection of regulatory sites were constructed using the available experimental data on archaeal transcription regulation or by analogy with known bacterial regulons, and further analysis was performed using iterativ e profile searches. The information content of the candidate signals detect ed by this method is insufficient for reliable predictions to be made. Ther efore, this approach has to be complemented by examination of evolutionary conservation in different archaeal genomes. This combined strategy resulted in the prediction of a conserved heat shock regulon in all euryarchaea, a nitrogen fixation regulon in the methanogens Methanococcus jannaschii and M ethanobacterium thermoautotrophicum and an aromatic amino acid regulon in M . thermoautotrophicum. Unexpectedly, the heat shock regulatory site was det ected not only for genes that encode known chaperone proteins but also for archaeal histone genes. This suggests a possible function for archaeal hist ones in stress-related changes in DNA condensation. In addition, comparativ e analysis of the genomes of three Pyrococcus species resulted in the predi ction of their purine metabolism and transport regulon, The results demonst rate the feasibility of prediction of at least some transcription regulator y sites by comparing poorly characterized prokaryotic genomes, particularly when several closely related genome sequences are available.