Automatic detection of conserved base pairing patterns in RNA virus genomes

Almost all RNA molecules-and consequently also almost all subsequences of a large RNA molecule-form secondary structures. The presence of secondary st ructure in itself therefore does not indicate any functional significance. In fact, we cannot expect a conserved secondary structure for all parts of a viral genome or a mRNA, even if there is a significant level of sequence conservation. We present a novel method for detecting conserved RNA seconda ry structures in a family of related RNA sequences. The method is based on combining the prediction of base pair probability matrices and comparative sequence analysis. It can be applied to small sets of long sequences and do es not require a prior knowledge of conserved sequence or structure motifs. As such it can be used to scan large amounts of sequence data for regions that warrant further experimental investigation. Applications to complete g enomic RNAs of some viruses show that in all cases the known secondary stru cture features are identified. In addition, we predict a substantial number of conserved structural elements which have not been described so far. (C) 1999 Elsevier Science Ltd. All rights reserved.