Conserved intron positions in ancient protein modules

BACKGROUND: The timing of the origin of introns is of crucial importance for an understanding of early genome architecture. The Exon theory of genes proposed a role for introns in the formation of multi-exon proteins by exon shuffling and predicts the presence of conserved splice sites in ancient genes. In this study, large-scale analysis of potential conserved splice sites was performed using an intron-exon database (ExInt) derived from GenBank. RESULTS: A set of conserved intron positions was found by matching identical splice sites sequences from distantly-related eukaryotic kingdoms. Most amino acid sequences with conserved introns were homologous to consensus sequences of functional domains from conserved proteins including kinases, phosphatases, small GTPases, transporters and matrix proteins. These included ancient proteins that originated before the eukaryote-prokaryote split, for instance the catalytic domain of protein phosphatase 2A where a total of eleven conserved introns were found. Using an experimental setup in which the relation between a splice site and the ancientness of its surrounding sequence could be studied, it was found that the presence of an intron was positively correlated to the ancientness of its surrounding sequence. Intron phase conservation was linked to the conservation of the gene sequence and not to the splice site sequence itself. However, no apparent differences in phase distribution were found between introns in conserved versus non-conserved sequences. CONCLUSION: The data confirm an origin of introns deep in the eukaryotic branch and is in concordance with the presence of introns in the first functional protein modules in an 'Exon theory of genes' scenario. A model is proposed in which shuffling of primordial short exonic sequences led to the formation of the first functional protein modules, in line with hypotheses that see the formation of introns integral to the origins of genome evolution. REVIEWERS: This article was reviewed by Scott Roy (nominated by Anthony Poole), Sandro de Souza (nominated by Manyuan Long), and Gáspár Jékely

Modelling evolution on design-by-contract predicts an origin of Life through an abiotic double-stranded RNA world

BACKGROUND: It is generally believed that life first evolved from single-stranded RNA (ssRNA) that both stored genetic information and catalyzed the reactions required for self-replication. PRESENTATION OF THE HYPOTHESIS: By modeling early genome evolution on the engineering paradigm design-by-contract, an alternative scenario is presented in which life started with the appearance of double-stranded RNA (dsRNA) as an informational storage molecule while catalytic single-stranded RNA was derived from this dsRNA template later in evolution. TESTING THE HYPOTHESIS: It was investigated whether this scenario could be implemented mechanistically by starting with abiotic processes. Double-stranded RNA could be formed abiotically by hybridization of oligoribonucleotides that are subsequently non-enzymatically ligated into a double-stranded chain. Thermal cycling driven by the diurnal temperature cycles could then replicate this dsRNA when strands of dsRNA separate and later rehybridize and ligate to reform dsRNA. A temperature-dependent partial replication of specific regions of dsRNA could produce the first template-based generation of catalytic ssRNA, similar to the developmental gene transcription process. Replacement of these abiotic processes by enzymatic processes would guarantee functional continuity. Further transition from a dsRNA to a dsDNA world could be based on minor mutations in template and substrate recognition sites of an RNA polymerase and would leave all existing processes intact. IMPLICATIONS OF THE HYPOTHESIS: Modeling evolution on a design pattern, the 'dsRNA first' hypothesis can provide an alternative mechanistic evolutionary scenario for the origin of our genome that preserves functional continuity. REVIEWERS: This article was reviewed by Anthony Poole, Eugene Koonin and Eugene Shakhnovic

Pulmonary flow profile and distensibility following acute pulmonary embolism

<p>Abstract</p> <p>Objective</p> <p>Proof of concept study evaluating CMR as screening tool for chronic thromboembolic pulmonary hypertension (CTEPH) in patients treated for acute pulmonary embolism (PE).</p> <p>Materials and methods</p> <p>Right and left ventricular function of 15 consecutive patients treated for PE and 10 consecutive patients in whom PE was excluded was estimated at baseline by cardiac CT and at 6 months follow-up by CMR. Additionally, during the follow-up visit, pulmonary artery (PA) hemodynamics were studied by CMR and the presence of pulmonary hypertension by echocardiography.</p> <p>Results</p> <p>CT measured right ventricular ejection fraction (RVEF) was lower in patients with PE compared to patients without PE at time of diagnosis (median 47%, interquartile range 39-53 vs. 55%, 52-58; p = 0.014). After 6 months follow up, the RVEF between patients treated for PE and patients without PE were not statistically significant different (55%, 52-60 versus 54%, 51-57; p = 0.57), as were distensibility index (0.18 ± 0.18 versus 0.25 ± 0.18, p = 0.20), mean velocity (14.1 ± 3.9 cm/s versus 14.0 ± 2.5 cm/s, p = 0.81), peak velocity (86.5 ± 22 cm/s versus 89.6 ± 13 cm/s, p = 0.43) and time to peak PA blood flow velocity (142 ± 49 ms versus 161 ± 29 ms, p = 0.14). One patient was diagnosed with CTEPH and CMR revealed poor right systolic function, decreased PA distensibility and flow velocity, and a systolic notch in the PA flow profile consistent with persistent PA obstruction.</p> <p>Conclusion</p> <p>In this small series, right ventricular performance and PA flow profiles of patients treated for 6 months after PE are equivalent to those parameters in normal patients.</p

Assessment of coronary artery calcium by using volumetric 320-row multi-detector computed tomography: comparison of 0.5 mm with 3.0 mm slice reconstructions

The purpose of this study was to assess the performance of 0.5 versus 3.0 mm slice reconstructions in depicting coronary calcium with special attention to patients having zero calcium scores at 3.0 mm reconstructions by using computed tomography (CT). Imaging was performed by volumetric 320-detector row CT. Scans of 100 patients with a negative and 100 patients with a positive Agatston score at 3.0 mm reconstructions were consecutively selected. Non-overlapping volume sets with 3.0 and 0.5 mm slice thickness were reconstructed from the same raw data and Agatston and volume scores were obtained. The Wilcoxon signed ranks test was used to determine statistical differences between 3.0 and 0.5 mm calcium scores. Agatston and volume scores obtained at 0.5 mm were significantly higher than at 3.0 mm reconstructions (mean Agatston score: 266 ± 495 vs. 231 ± 461. Mean volume score: 223 ± 399 vs. 206 ± 385, both P < 0.01). In 21% of patients with zero 3.0 mm Agatston scores, a positive Agatston and/or volume score was found at 0.5 mm reconstructions. With volumetric 320-detector row CT, prospective ECG-triggered calcium scoring at 0.5 mm compared to 3.0 mm reconstructions leads to an increase in Agatston and volume scores and small amounts of coronary calcium are earlier depicted. This may be of special interest in patients with zero calcium scores with traditional 3.0 mm measures, where 0.5 mm reconstructions may help in superior depicting or ruling out coronary artery disease

Meeting Highlights of the 11th Annual Scientific Sessions of the Society for Cardiovascular Magnetic Resonance, Los Angeles, February 1–3, 2008

This paper features the most interesting presentations and discussions of the 2008 Annual Sessions of the Society for Cardiovascular Magnetic Resonance, which were held in Los Angeles from February 1 to 3, 2008