title: Effects of using coding potential, sequence conservation and mRNA structure conservation for predicting pyrrolysine containing genes.
abstract: BACKGROUND
  Pyrrolysine (the 22nd amino acid) is in certain organisms and under certain circumstances encoded by the amber stop codon, UAG. The circumstances driving pyrrolysine translation are not well understood. The involvement of a predicted mRNA structure in the region downstream UAG has been suggested, but the structure does not seem to be present in all pyrrolysine incorporating genes.
  
  
  RESULTS
  We propose a strategy to predict pyrrolysine encoding genes in genomes of archaea and bacteria. We cluster open reading frames interrupted by the amber codon based on sequence similarity. We rank these clusters according to several features that may influence pyrrolysine translation. The ranking effects of different features are assessed and we propose a weighted combination of these features which best explains the currently known pyrrolysine incorporating genes. We devote special attention to the effect of structural conservation and provide further substantiation to support that structural conservation may be influential - but is not a necessary factor. Finally, from the weighted ranking, we identify a number of potentially pyrrolysine incorporating genes.
  
  
  CONCLUSIONS
  We propose a method for prediction of pyrrolysine incorporating genes in genomes of bacteria and archaea leading to insights about the factors driving pyrrolysine translation and identification of new gene candidates. The method predicts known conserved genes with high recall and predicts several other promising candidates for experimental verification. The method is implemented as a computational pipeline which is available on request.
authors.affiliation: Research group PLIS: Programming, Logic and Intelligent Systems, Department of Communication, Business and Information Technologies, Roskilde University, P.O. Box 260, Roskilde, DK-4000, Denmark. cth@ruc.dk
authors.forename: Christian
authors.initials: C
authors.lastname: Theil Have
authors.forename: Sine
authors.initials: S
authors.lastname: Zambach
authors.forename: Henning
authors.initials: H
authors.lastname: Christiansen
mesh_terms: D001483:Base Sequence; D016000:Cluster Analysis; D018388:Codon, Terminator; D017124:Conserved Sequence; D019143:Evolution, Molecular; D020745:Genome, Archaeal; D016680:Genome, Bacterial; D023281:Genomics / Q000379:methods; D008239:Lysine / Q000031:analogs & derivatives* / Q000235:genetics; D008780:Methyltransferases / Q000235:genetics; D016366:Open Reading Frames; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000737:chemistry*; D016415:Sequence Alignment
chemical_list: D018388:Codon, Terminator; D012333:RNA, Messenger; D008780:Methyltransferases; C456839:pyrrolysine; D008239:Lysine
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