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The flagellum is a key innovation linked to eukaryogenesis. It provides motility by regulated cycles of bending and bend propagation, which are thought to be controlled by a complex arrangement of seven distinct dyneins in repeated patterns of outer- (OAD) and inner-arm dynein (IAD) complexes. Electron tomography showed high similarity of this axonemal repeat pattern across ciliates, algae, and animals, but the diversity of dynein sequences across the eukaryotes has not yet comprehensively been resolved and correlated with structural data. To shed light on the evolution of the axoneme I performed an exhaustive analysis of dyneins using the available sequenced genome data. Evidence frommotor domain phylogeny allowed expanding the current set of nine dynein subtypes by eight additional isoforms with, however, restricted taxonomic distributions. I confirmed the presence of the nine dyneins in all eukaryotic super-groups indicating their origin predating the last eukaryotic common ancestor. The comparison of the N-terminal tail domains revealed a most likely axonemal dynein origin of the new classes, a group of chimeric dyneins in plants/algae and Stramenopiles, and the unique domain architecture and origin of the outermost OADs present in green algae and ciliates but not animals. The correlation of sequence and structural data suggests the single-headed class-8 and class-9 dyneins to localize to the distal end of the axonemal repeat and the class-7 dyneins filling the region up to the proximal heterodimeric IAD. Tracing dynein gene duplications across the eukaryotes indicated ongoing diversification and fine-tuning of flagellar functions in extant taxa and species. [ABSTRACT FROM AUTHOR]

The universal genetic code defines the translation of nucleotide triplets, called codons, into amino acids. In many Saccharomycetes a unique alteration of this code affects the translation of the CUG codon, which is normally translated as leucine. Most of the species encoding CUG alternatively as serine belong to the Candida genus and were grouped into a so-called CTG clade. However, the "Candida genus" is not a monophyletic group and several Candida species are known to use the standard CUG translation. The codon identity could have been changedin a single branch, the ancestor of the Candida, or toseveral branches independently leading to a polyphyletic alternative yeast codon usage (AYCU). In order to resolve themonophyly or polyphyly of theAYCU,weperformed a phylogenomics analysis of 26 motor and cytoskeletal proteins from 60 sequenced yeast species. By investigating the CUG codon positions with respect to sequence conservation at the respective alignment positions, we were able to unambiguously assign the standard code orAYCU.Quantitative analysis of the highly conserved leucine and serine alignment positions showedthat61.1%and 17%of the CUGcodons coding for leucine and serine, respectively, are at highly conserved positions, whereas only 0.6%and 2.3% of the CUG codons, respectively, are at positions conserved in the respective other amino acid. Plotting the codon usage onto the phylogenetic tree revealed the polyphyly of the AYCU with Pachysolen tannophilus and the CTG clade branching independently within a time span of 30-100 Ma. [ABSTRACT FROM AUTHOR]

Tubulins belong to the most abundant proteins in eukaryotes providing the backbone for many cellular substructures like the mitotic and meiotic spindles, the intracellular cytoskeletal network, and the axonemes of cilia and flagella. Homologs have even been reported for archaea and bacteria. However, a taxonomically broad and whole-genome-based analysis of the tubulin protein family has never been performed, and thus, the number of subfamilies, their taxonomic distribution, and the exact grouping of the supposed archaeal and bacterial homologs are unknown. Here, we present the analysis of 3,524 tubulins from 504 species. The tubulins formed six major subfamilies, α to ζ. Species of all major kingdoms of the eukaryotes encode members of these subfamilies implying that they must have already been present in the last common eukaryotic ancestor. The proposed archaeal homologs grouped together with the bacterial TubZ proteins as sister clade to the FtsZ proteins indicating that tubulins are unique to eukaryotes. Most species contained α- and/or β-tubulin gene duplicates resulting from recent branch- and species-specific duplication events. This shows that tubulins cannot be used for constructing species phylogenies without resolving their ortholog–paralog relationships. The many gene duplicates and also the independent loss of the δ-, ε-, or ζ-tubulins, which have been shown to be part of the triplet microtubules in basal bodies, suggest that tubulins can functionally substitute each other. [ABSTRACT FROM AUTHOR]

Motivation: When analyzing solid-state nuclear magnetic resonance (NMR) spectra of proteins, assignment of resonances to nuclei and derivation of restraints for 3D structure calculations are challenging and time-consuming processes. Simulated spectra that have been calculated based on, for example, chemical shift predictions and structural models can be of considerable help. Existing solutions are typically limited in the type of experiment they can consider and difficult to adapt to different settings.Results: Here, we present Peakr, a software to simulate solid-state NMR spectra of proteins. It can generate simulated spectra based on numerous common types of internuclear correlations relevant for assignment and structure elucidation, can compare simulated and experimental spectra and produces lists and visualizations useful for analyzing measured spectra. Compared with other solutions, it is fast, versatile and user friendly.Availability and implementation: Peakr is maintained under the GPL license and can be accessed at http://www.peakr.org. The source code can be obtained on request from the authors.Contact: robert.schneider@ibs.fr or mako@nmr.mpibpc.mpg.deSupplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Motivation: As improved DNA sequencing techniques have increased enormously the speed of producing new eukaryotic genome assemblies, the further development of automated gene prediction methods continues to be essential.While the classification of proteins into families is a task heavily relying on correct gene predictions, it can at the same time provide a source of additional information for the prediction, complementary to those presently used.Results: We extended the gene prediction software AUGUSTUS by a method that employs block profiles generated from multiple sequence alignments as a protein signature to improve the accuracy of the prediction. Equipped with profiles modelling human dynein heavy chain (DHC) proteins and other families, AUGUSTUS was run on the genomic sequences known to contain members of these families. Compared with AUGUSTUS' ab initio version, the rate of genes predicted with high accuracy showed a dramatic increase.Availability: The AUGUSTUS project web page is located at http://augustus.gobics.de, with the executable program as well as the source code available for download.Contact: keller@cs.uni-goettingen.de; mario.stanke@uni-greifswald.deSupplementary information: Supplementary data are available at Bioinformatics online. [ABSTRACT FROM AUTHOR]

Conserved intron positions in eukaryotic genes can be used to reconstruct phylogenetic trees, to resolve ambiguous subfamily relationships in protein families and to infer the history of gene families. This version of GenePainter facilitates working with large datasets through options to select specific subsets for analysis and visualization, and through providing exhaustive statistics. GenePainter's application in phylogenetic analyses is considerably extended by the newly implemented integration of the exon-intron pattern conservation with phylogenetic trees. [ABSTRACT FROM AUTHOR]

Summary: Waggawagga is a web-based tool for the comparative visualization of coiled-coil predictions and the detection of stable single α-helices (SAH domains). Overview schemes show the predicted coiled-coil regions found in the query sequence and provide sliders, which can be used to select segments for detailed helical wheel and helical net views. A window-based score has been developed to predict SAH domains. Export to several bitmap and vector graphics formats is supported.Availability and implementation: http://waggawagga.motorprotein.deContact: mako@nmr.mpibpc.mpg.de [ABSTRACT FROM PUBLISHER]

Summary: Dynamics governing the function of biomolecule is usually described as exchange processes and can be monitored at atomic resolution with nuclear magnetic resonance (NMR) relaxation dispersion data. Here, we present a new tool for the analysis of CPMG relaxation dispersion profiles (ShereKhan). The web interface to ShereKhan provides a user-friendly environment for the analysis.Availability: A stable version of ShereKhan, the web application and documentation are available at http://sherekhan.bionmr.org.Contact: dole@nmr.mpibpc.mpg.de or mako@nmr.mpibpc.mpg.de [ABSTRACT FROM AUTHOR]

The article notes that the article "Molecular Phylogeny of Sequenced Saccharomycetes Reveals Polyphyly of the Alternative Yeast Codon Usage" by Stefanie Mühlhausen and Martin Kollmar has been retracted until the data underlying the paper will be resolved.

Dystonia musculorum is a neurodegenerative disorder caused by a mutation in the dystonin gene. It has been described in mice and humans where it is called hereditary sensory autonomic neuropathy. Mutated mice show severe movement disorders and die at the age of 3-4 weeks. This study describes the discovery and molecular, clinical, as well as pathological characterization of a new spontaneously occurring mutation in the dystonin gene in C57BL/6N mice. The mutation represents a 40-kb intragenic deletion allele of the dystonin gene on chromosome 1 with exactly defined deletion borders. It was demonstrated by Western blot, mass spectrometry, and immunohistology that mice with a homozygous mutation were entirely devoid of the dystonin protein. Pathomorphological lesions were restricted to the brain stem and spinal cord and consisted of swollen, argyrophilic axons and dilated myelin sheaths in the white matter and, less frequently, total chromatolysis of neurons in the gray matter. Axonal damage was detected by amyloid precursor protein and nonphosphorylated neurofilament immunohistology. Axonopathy in the central nervous system (CNS) represents the hallmark of this disease. Mice with the dystonin mutation also showed suppurative inflammation in the respiratory tract, presumably due to brain stem lesion-associated food aspiration, whereas skeletal muscles showed no pathomorphological changes. This study describes a novel mutation in the dystonin gene in mice leading to axonopathy in the CNS. In further studies, this model may provide new insights into the pathogenesis of neurodegenerative diseases and may elucidate the complex interactions of dystonin with various other cellular proteins especially in the CNS. [ABSTRACT FROM AUTHOR]