Bioinformatics Preprint 07-001
Computational RNomics of Drosophilids
Dominic Rose, Jörg Hackermüller, Stefan Washietl, Sven Findei&zslig;, Kristin Reiche, Jana Hertel, Peter F. Stadler, Sonja J. Prohaska
Recent experimental and computational studies have provided overwhelming evidence for a plethora of diverse transcripts that are unrelated to protein-coding genes. One subclass consists of those RNAs that require distinctive secondary structure motifs to exert their biological function and hence exhibit distinctive patterns of sequence conservation characteristic for positive selection on RNA secondary structure. The deep-sequencing of 12 Drosophilid species by the BDGB provides an ideal data set of comparative computational approaches to determine those genomic loci that code for evolutionarily conserved RNA motifs. This class of loci include the majority of the known small ncRNAs as well as structured RNA motifs in mRNAs. We report here on a genome-wide survey using RNAz. We obtain 16.000 high quality predictions among which we recover the majority of the known ncRNAs. Taking a pessimistically estimated false discovery rate of 40% into account, this implies that at least some ten thousand loci in the Drosophila genome show the hallmarks of stabilizing selection action of RNA structure, and hence are most likely functional at the RNA level. A subset of RNAz predictions overlapping with TRF1 and BRF binding sites [Isogai et al., EMBO J., Epub Dec 2006], which are plausible candidates of pol-III transcripts have been studied in more detail. Among these sequence we identify several ``clusters'' of ncRNA candidates with striking structural similarities. The statistical evaluation of the RNAz predictions in comparison with a similar analysis of vertebrate genomes [Washietl et al., Nat.Biotech. 23: 1383-1390 (2005)] shows that qualitatively similar fractions of structured RNAs are found in introns, UTRs, and intergenic regions. The intergenic RNA structures, however, are concentrated much more closely around known protein-coding loci, suggesting that flies have significantly smaller complement of independent structured ncRNAs compared to mammals. Keywords: Drosophilid, comparative genomics, ncRNAs, RNA secondary structure
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