Conservation of intron and intein insertion sites: implications for life histories of parasitic genetic elements

<p>Abstract</p> <p>Background</p> <p>Inteins and introns are genetic elements that are removed from proteins and RNA after translation or transcription, respectively. Previous studies have suggested that these genetic elements are found in conserved parts of the host protein. To our knowledge this type of analysis has not been done for group II introns residing within a gene. Here we provide quantitative statistical support from an analyses of proteins that host inteins, group I introns, group II introns and spliceosomal introns across all three domains of life.</p> <p>Results</p> <p>To determine whether or not inteins, group I, group II, and spliceosomal introns are found preferentially in conserved regions of their respective host protein, conservation profiles were generated and intein and intron positions were mapped to the profiles. Fisher's combined probability test was used to determine the significance of the distribution of insertion sites across the conservation profile for each protein. For a subset of studied proteins, the conservation profile and insertion positions were mapped to protein structures to determine if the insertion sites correlate to regions of functional activity. All inteins and most group I introns were found to be preferentially located within conserved regions; in contrast, a bacterial intein-like protein, group II and spliceosomal introns did not show a preference for conserved sites.</p> <p>Conclusions</p> <p>These findings demonstrate that inteins and group I introns are found preferentially in conserved regions of their respective host proteins. Homing endonucleases are often located within inteins and group I introns and these may facilitate mobility to conserved regions. Insertion at these conserved positions decreases the chance of elimination, and slows deletion of the elements, since removal of the elements has to be precise as not to disrupt the function of the protein. Furthermore, functional constrains on the targeted site make it more difficult for hosts to evolve immunity to the homing endonuclease. Therefore, these elements will better survive and propagate as molecular parasites in conserved sites. In contrast, spliceosomal introns and group II introns do not show significant preference for conserved sites and appear to have adopted a different strategy to evade loss.</p

Variation in cell signaling protein expression may introduce sampling bias in primary epithelial ovarian cancer.

Although the expression of cell signaling proteins is used as prognostic and predictive biomarker, variability of protein levels within tumors is not well studied. We assessed intratumoral heterogeneity of protein expression within primary ovarian cancer. Full-length proteins were extracted from 88 formalin-fixed and paraffin-embedded tissue samples of 13 primary high-grade serous ovarian carcinomas with 5-9 samples each. In addition, 14 samples of normal fallopian tube epithelium served as reference. Quantitative reverse phase protein arrays were used to analyze the expression of 36 cell signaling proteins including HER2, EGFR, PI3K/Akt, and angiogenic pathways as well as 15 activated (phosphorylated) proteins. We found considerable intratumoral heterogeneity in the expression of proteins with a mean coefficient of variation of 25% (range 17-53%). The extent of intratumoral heterogeneity differed between proteins (p<0.005). Interestingly, there were no significant differences in the extent of heterogeneity between phosphorylated and non-phosphorylated proteins. In comparison, we assessed the variation of protein levels amongst tumors from different patients, which revealed a similar mean coefficient of variation of 21% (range 12-48%). Based on hierarchical clustering, samples from the same patient clustered more closely together compared to samples from different patients. However, a clear separation of tumor versus normal tissue by clustering was only achieved when mean expression values of all individual samples per tumor were analyzed. While differential expression of some proteins was detected independently of the sampling method used, the majority of proteins only demonstrated differential expression when mean expression values of multiple samples per tumor were analyzed. Our data indicate that assessment of established and novel cell signaling proteins as diagnostic or prognostic markers may require sampling of serous ovarian cancers at several distinct locations to avoid sampling bias

Klimaentwicklung und Klimaszenarien

In den letzten Jahren hat sich das Wissen um mögliche Folgen des Klimawandels durch zahlreiche Untersuchungen ständig verbessert. Dabei stehen für Deutschland und Niedersachsen vor allem wachsende Hitzebelastungen, Zunahme von Extremwetterereignissen und der Anstieg des Meeresspiegels im Fokus. Im Forschungsverbund KLIFF „Klimafolgenforschung in Niedersachsen“ wurde für Niedersachsen zum Ende des Jahrhunderts (2071-2100) im Vergleich zur Referenzperiode 1971-2000 eine Erhöhung der Jahresmitteltemperatur um ca. 2,5 Grad projiziert, wobei der Anstieg im Winter mit etwa 3 Grad am höchsten ausfällt. Mit der höheren Temperatur kann auch die Länge der Vegetationsperiode zunehmen: bis um circa 60 Tage bis zum Ende des Jahrhunderts; entsprechend kann sich die Anzahl der Frosttage um circa zwei Drittel verringern. Die Klimaforscher erwarten, dass die Niederschläge zum Ende des Jahrhunderts im Winter, Frühling und Herbst zunehmen können, für den Sommer wird eine Abnahme um rund 10 Prozent in Niedersachsen projiziert. Die Anzahl der Starkniederschlagstage kann sich nach den Berechnungen deutlich erhöhen, insbesondere im Herbst. Die mittlere Dauer von Wärmeperioden könnte im Sommer um 50 Prozent zunehmen

Comparison of intratumoral heterogeneity and variation among patients for all proteins, phosphorylated and non-phosphorylated proteins.

<p>CV, coefficient of variation.</p><p>Overall, all proteins combined; Phospho, all phosphorylated proteins combined; Non-phospho, all non-phosphorylated proteins combined.</p><p>Healthy tubes, fallopian tube epithelium from healthy individuals.</p><p>Contralateral tubes, morphologically normal contralateral fallopian tube epithelium from ovarian cancer patients.</p

Variation between 88 individual tumor samples from 13 patients assessed by non-supervised hierarchical clustering based on expression of 36 proteins.

<p>Different patients are color-coded as indicated in the figure legend. High relative expression of proteins is shown in red and low expression in green color. Grey spaces indicate missing data points.</p