The EH1 motif in metazoan transcription factors

BACKGROUND: The Engrailed Homology 1 (EH1) motif is a small region, believed to have evolved convergently in homeobox and forkhead containing proteins, that interacts with the Drosophila protein groucho (C. elegans unc-37, Human Transducin-like Enhancers of Split). The small size of the motif makes its reliable identification by computational means difficult. I have systematically searched the predicted proteomes of Drosophila, C. elegans and human for further instances of the motif. RESULTS: Using motif identification methods and database searching techniques, I delimit which homeobox and forkhead domain containing proteins also have likely EH1 motifs. I show that despite low database search scores, there is a significant association of the motif with transcription factor function. I further show that likely EH1 motifs are found in combination with T-Box, Zinc Finger and Doublesex domains as well as discussing other plausible candidate associations. I identify strong candidate EH1 motifs in basal metazoan phyla. CONCLUSION: Candidate EH1 motifs exist in combination with a variety of transcription factor domains, suggesting that these proteins have repressor functions. The distribution of the EH1 motif is suggestive of convergent evolution, although in many cases, the motif has been conserved throughout bilaterian orthologs. Groucho mediated repression was established prior to the evolution of bilateria

POPE—a tool to aid high-throughput phylogenetic analysis

Summary: POPE (Phylogeny, Ortholog and Paralog Extractor) provides an integrated platform for automatic ortholog identification. Intermediate steps can be visualized, modified and analyzed in order to assess and improve the underlying quality of orthology and paralogy assignments

Variation in structural location and amino acid conservation of functional sites in protein domain families

BACKGROUND: The functional sites of a protein present important information for determining its cellular function and are fundamental in drug design. Accordingly, accurate methods for the prediction of functional sites are of immense value. Most available methods are based on a set of homologous sequences and structural or evolutionary information, and assume that functional sites are more conserved than the average. In the analysis presented here, we have investigated the conservation of location and type of amino acids at functional sites, and compared the behaviour of functional sites between different protein domains. RESULTS: Functional sites were extracted from experimentally determined structural complexes from the Protein Data Bank harbouring a conserved protein domain from the SMART database. In general, functional (i.e. interacting) sites whose location is more highly conserved are also more conserved in their type of amino acid. However, even highly conserved functional sites can present a wide spectrum of amino acids. The degree of conservation strongly depends on the function of the protein domain and ranges from highly conserved in location and amino acid to very variable. Differentiation by binding partner shows that ion binding sites tend to be more conserved than functional sites binding peptides or nucleotides. CONCLUSION: The results gained by this analysis will help improve the accuracy of functional site prediction and facilitate the characterization of unknown protein sequences

HSPG Modification by the Secreted Enzyme Notum Shapes the Wingless Morphogen Gradient

AbstractThe secreted signaling protein Wingless acts as a morphogen to pattern the imaginal discs of Drosophila. Here we report identification of a secreted repressor of Wingless activity, which we call Notum. Loss of Notum function leads to increased Wingless activity by altering the shape of the Wingless protein gradient. When overexpressed, Notum blocks Wingless activity. Notum encodes a member of the α/β-hydrolase superfamily, with similarity to pectin acetylesterases. We present evidence that Notum influences Wingless protein distribution by modifying the heparan sulfate proteoglycans Dally-like and Dally. High levels of Wingless signaling induce Notum expression. Thus, Wingless contributes to shaping its own gradient by regulating expression of a protein that modifies its interaction with cell surface proteoglycans

A High-Resolution Single Nucleotide Polymorphism Genetic Map of the Mouse Genome

High-resolution genetic maps are required for mapping complex traits and for the study of recombination. We report the highest density genetic map yet created for any organism, except humans. Using more than 10,000 single nucleotide polymorphisms evenly spaced across the mouse genome, we have constructed genetic maps for both outbred and inbred mice, and separately for males and females. Recombination rates are highly correlated in outbred and inbred mice, but show relatively low correlation between males and females. Differences between male and female recombination maps and the sequence features associated with recombination are strikingly similar to those observed in humans. Genetic maps are available from http://gscan.well.ox.ac.uk/#genetic_map and as supporting information to this publication

SMART 5: domains in the context of genomes and networks

The Simple Modular Architecture Research Tool (SMART) is an online resource () used for protein domain identification and the analysis of protein domain architectures. Many new features were implemented to make SMART more accessible to scientists from different fields. The new ‘Genomic’ mode in SMART makes it easy to analyze domain architectures in completely sequenced genomes. Domain annotation has been updated with a detailed taxonomic breakdown and a prediction of the catalytic activity for 50 SMART domains is now available, based on the presence of essential amino acids. Furthermore, intrinsically disordered protein regions can be identified and displayed. The network context is now displayed in the results page for more than 350 000 proteins, enabling easy analyses of domain interactions

Identification of differentially expressed genes from multipotent epithelia at the onset of an asexual development

© The Author(s), 2016. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Scientific Reports 6 (2016): 27357, doi:10.1038/srep27357.Organisms that have evolved alternative modes of reproduction, complementary to the sexual mode, are found across metazoans. The chordate Botryllus schlosseri is an emerging model for asexual development studies. Botryllus can rebuild its entire body from a portion of adult epithelia in a continuous and stereotyped process called blastogenesis. Anatomy and ontogenies of blastogenesis are well described, however molecular signatures triggering this developmental process are entirely unknown. We isolated tissues at the site of blastogenesis onset and from the same epithelia where this process is never triggered. We linearly amplified an ultra-low amount of mRNA (<10ng) and generated three transcriptome datasets. To provide a conservative landscape of transcripts differentially expressed between blastogenic vs. non-blastogenic epithelia we compared three different mapping and analysis strategies with a de novo assembled transcriptome and partially assembled genome as references, additionally a self-mapping strategy on the dataset. A subset of differentially expressed genes were analyzed and validated by in situ hybridization. The comparison of different analyses allowed us to isolate stringent sets of target genes, including transcripts with potential involvement in the onset of a non-embryonic developmental pathway. The results provide a good entry point to approach regenerative event in a basal chordate.This work was supported by AFM Telethon grant (#16611), IRG Marie Curie grant (#276974), ANR (ANR-14-CE02-0019-01) and IDEX Super (INDIBIO). L.R. was supported by an UPMC-EMREGENCE grant and by a FRM grant (#FDT20140931163). A.C. was supported by a FRM grant (ING 20140129231)

Oroclinal bending, distributed thrust and strike-slip faulting, and the accommodation of Arabia–Eurasia convergence in NE Iran since the Oligocene

Regional shortening is accommodated across NE Iran in response to the collision of Arabia with Eurasia. We examine how N–S shortening is achieved on major thrust systems bounding the eastern branch of the Alborz (east of 57°E), Sabzevar and Kuh-e-Sorkh mountain ranges, which lie south of the Kopeh Dagh mountains in NE Iran. Although these ranges have experienced relatively few large earthquakes over the last 50 yr, they have been subject to a number of devastating historical events at Neyshabur, Esfarayen and Sabzevar. A significant change in the tectonics of the eastern Alborz occurs directly south of the Central Kopeh Dagh, near 57°E. To the east, shortening occurs on major thrust faults which bound the southern margin of the range, resulting in significant crustal thickening, and forming peaks up to 3000 m high. Active shortening dies out eastward into Afghanistan, which is thought to belong to stable Eurasia. The rate of shortening across thrust faults bounding the south side of the eastern Alborz north of Neyshabur is determined using optically stimulated luminescence dating of displaced river deposits, and is likely to be 0.4–1.7 mm yr^(−1). Shortening across the Sabzevar range 150 km west of Neyshabur has previously been determined at 0.4–0.6 mm yr^(−1), although reassessment of the rate here suggests it may be as high as 1 mm yr^(−1). Migration of thrust faulting into foreland basins is common across NE Iran, especially in the Esfarayen region near 57°E, where the northward deflection of the East Alborz range reaches a maximum of 200 ± 20 km (from its presumed linear E–W strike at the beginning of the Oligocene). West of 57°E, the tectonics of the Alborz are affected by the westward motion of the South Caspian region, which results in the partitioning of shortening onto separate thrust and left-lateral strike-slip faults north and south of the range. At the longitude of 59°E, published GPS velocities indicate that 50 per cent of the overall shortening across NE Iran is accommodated in the Kopeh Dagh. The remaining 50 per cent regional shortening must therefore be accommodated south of the Kopeh Dagh, in the eastern Alborz and Kuh-e-Sorkh ranges. Assuming present day rates of slip and the fault kinematics are representative of the Late Cenozoic deformation in NE Iran, the total 200 ± 20 km N–S shortening across the eastern Alborz and Kopeh Dagh mountains since the beginning of uplift of the Kopeh Dagh basin would be accommodated in 30 ± 8 Ma. Although this extrapolation may be inappropriate over such a long timescale, the age is nevertheless consistent with geological estimates of post Early-to-Middle Oligocene (<30 Ma) for the onset of Kopeh Dagh uplift

Charmed and Bottom Baryons: a Variational Approach based on Heavy Quark Symmetry

The use of Heavy Quark Symmetry to study bottom and charmed baryons leads to important simplifications of the non-relativistic three body problem, which turns out to be easily solved by a simple variational ansatz. Our simple scheme reproduces previous results (baryon masses, charge and mass radii, $...$) obtained by solving the Faddeev equations with simple non-relativistic quark--quark potentials, adjusted to the light and heavy--light meson spectra. Wave functions, parameterized in a simple manner, are also given and thus they can be easily used to compute further observables. Our method has been also used to find the predictions for strangeness-less baryons of the SU(2) chirally inspired quark-quark interactions. We find that the one pion exchange term of the chirally inspired interactions leads to relative changes of the $\Lambda_b$ and $\Lambda_c$ binding energies as large as 90%.Comment: 20 pages, 5 figures. Revised version to be published in Nucl. Phys.