http://hdl.handle.net/2144/2701 2013-05-23T02:18:42Z http://hdl.handle.net/2144/3440 GTPases and the Origin of the Ribosome Hartman, Hyman; Smith, Temple F BACKGROUND. This paper is an attempt to trace the evolution of the ribosome through the evolution of the universal P-loop GTPases that are involved with the ribosome in translation and with the attachment of the ribosome to the membrane. The GTPases involved in translation in Bacteria/Archaea are the elongation factors EFTu/EF1, the initiation factors IF2/aeIF5b + aeIF2, and the elongation factors EFG/EF2. All of these GTPases also contain the OB fold also found in the non GTPase IF1 involved in initiation. The GTPase involved in the signal recognition particle in most Bacteria and Archaea is SRP54. RESULTS. 1) The Elongation Factors of the Archaea based on structural considerations of the domains have the following evolutionary path: EF1→ aeIF2 → EF2. The evolution of the aeIF5b was a later event; 2) the Elongation Factors of the Bacteria based on the topological considerations of the GTPase domain have a similar evolutionary path: EFTu→ IF→2→EFG. These evolutionary sequences reflect the evolution of the LSU followed by the SSU to form the ribosome; 3) the OB-fold IF1 is a mimic of an ancient tRNA minihelix. CONCLUSION. The evolution of translational GTPases of both the Archaea and Bacteria point to the evolution of the ribosome. The elongation factors, EFTu/EF1, began as a Ras-like GTPase bringing the activated minihelix tRNA to the Large Subunit Unit. The initiation factors and elongation factor would then have evolved from the EFTu/EF1 as the small subunit was added to the evolving ribosome. The SRP has an SRP54 GTPase and a specific RNA fold in its RNA component similar to the PTC. We consider the SRP to be a remnant of an ancient form of an LSU bound to a membrane. REVIEWERS. This article was reviewed by George Fox, Leonid Mirny and Chris Sander. 2010-05-20T00:00:00Z http://hdl.handle.net/2144/3441 Constraining Ribosomal RNA Conformational Space Favaretto, Paola; Bhutkar, Arjun; Smith, Temple F. Despite the potential for many possible secondary-structure conformations, the native sequence of ribosomal RNA (rRNA) is able to find the correct and universally conserved core fold. This study reports a computational analysis investigating two mechanisms that appear to constrain rRNA secondary-structure conformational space: ribosomal proteins and rRNA sequence composition. The analysis was carried out by using rRNA–ribosomal protein interaction data for the Escherichia coli 16S rRNA and free energy minimization software for secondary-structure prediction. The results indicate that selection pressures on rRNA sequence composition and ribosomal protein–rRNA interaction play a key role in constraining the rRNA secondary structure to a single stable form. 2005-09-09T00:00:00Z http://hdl.handle.net/2144/3442 Transcription Factor Map Alignment of Promoter Regions Blanco, Enrique; Messeguer, Xavier; Smith, Temple F; Guigó, Roderic We address the problem of comparing and characterizing the promoter regions of genes with similar expression patterns. This remains a challenging problem in sequence analysis, because often the promoter regions of co-expressed genes do not show discernible sequence conservation. In our approach, thus, we have not directly compared the nucleotide sequence of promoters. Instead, we have obtained predictions of transcription factor binding sites, annotated the predicted sites with the labels of the corresponding binding factors, and aligned the resulting sequences of labels—to which we refer here as transcription factor maps (TF-maps). To obtain the global pairwise alignment of two TF-maps, we have adapted an algorithm initially developed to align restriction enzyme maps. We have optimized the parameters of the algorithm in a small, but well-curated, collection of human–mouse orthologous gene pairs. Results in this dataset, as well as in an independent much larger dataset from the CISRED database, indicate that TF-map alignments are able to uncover conserved regulatory elements, which cannot be detected by the typical sequence alignments. Synopsis Sequence comparisons and alignments are among the most powerful tools in research in biology. Since similar sequences play, in general, similar functions, identification of sequence conservation between two or more nucleotide or amino acid sequences is often used to infer common biological functionality. Sequence comparisons, however, have limitations; often similar functions are encoded by higher order elements which do not hold a univocal relationship to the underlying primary sequence. In consequence, similar functions are frequently encoded by diverse sequences. Promoter regions are a case in point. Often, promoter sequences of genes with similar expression patterns do not show conservation. This is because, even though their expression may be regulated by a similar arrangement of transcription factors, the binding sites for these factors may exhibit great sequence variability. To overcome this limitation, the authors obtain predictions of transcription factor binding sites on promoter sequences, and annotate the predicted sites with the labels of the corresponding transcription factors. They develop an algorithm—inspired in an early algorithm to align restriction enzyme maps—to align the resulting sequence of labels—the so-called TF-maps (transcription factor maps). They show that TF-map alignments are able to uncover conserved regulatory elements common to the promoter regions of co-regulated genes, but those regulatory elements cannot be detected by typical sequence alignments. 2006-05-26T00:00:00Z http://hdl.handle.net/2144/3439 The Origin and Evolution of the Ribosome Smith, Temple F; Lee, Jung C; Gutell, Robin R; Hartman, Hyman BACKGROUND. The origin and early evolution of the active site of the ribosome can be elucidated through an analysis of the ribosomal proteins' taxonomic block structures and their RNA interactions. Comparison between the two subunits, exploiting the detailed three-dimensional structures of the bacterial and archaeal ribosomes, is especially informative. RESULTS. The analysis of the differences between these two sites can be summarized as follows: 1) There is no self-folding RNA segment that defines the decoding site of the small subunit; 2) there is one self-folding RNA segment encompassing the entire peptidyl transfer center of the large subunit; 3) the protein contacts with the decoding site are made by a set of universal alignable sequence blocks of the ribosomal proteins; 4) the majority of those peptides contacting the peptidyl transfer center are made by bacterial or archaeal-specific sequence blocks. CONCLUSION. These clear distinctions between the two subunit active sites support an earlier origin for the large subunit's peptidyl transferase center (PTC) with the decoding site of the small subunit being a later addition to the ribosome. The main implications are that a single self-folding RNA, in conjunction with a few short stabilizing peptides, formed the precursor of the modern ribosomal large subunit in association with a membrane. REVIEWERS. This article was reviewed by Jerzy Jurka, W. Ford Doolittle, Eugene Shaknovich, and George E. Fox (nominated by Jerzy Jurka). 2008-04-22T00:00:00Z