ProCARs: Progressive Reconstruction of Ancestral Gene Orders

International audienceBackground: In the context of ancestral gene order reconstruction from extant genomes, there exist two main computational approaches: rearrangement-based, and homology-based methods. The rearrangement-based methods consist in minimizing a total rearrangement distance on the branches of a species tree. The homology-based methods consist in the detection of a set of potential ancestral contiguity features, followed by the assembling of these features into Contiguous Ancestral Regions (CARs). Results: In this paper, we present a new homology-based method that uses a progressive approach for both the detection and the assembling of ancestral contiguity features into CARs. The method is based on detecting a set of potential ancestral adjacencies iteratively using the current set of CARs at each step, and constructing CARs progressively using a 2-phase assembling method. We show the usefulness of the method through a reconstruction of the boreoeutherian ancestral gene order, and a comparison with three other homology-based methods: AnGeS, InferCARs and GapAdj. The program is written in Python, and the dataset used in this paper are available at http://bioinfo.lifl.fr/procars/

Translational machinery of the chaetognath Spadella cephaloptera: a transcriptomic approach to the analysis of cytosolic ribosomal protein genes and their expression

<p>Abstract</p> <p>Background</p> <p>Chaetognaths, or arrow worms, are small marine, bilaterally symmetrical metazoans. The objective of this study was to analyse ribosomal protein (RP) coding sequences from a published collection of expressed sequence tags (ESTs) from a chaetognath (<it>Spadella cephaloptera</it>) and to use them in phylogenetic studies.</p> <p>Results</p> <p>This analysis has allowed us to determine the complete primary structures of 23 out of 32 RPs from the small ribosomal subunit (SSU) and 32 out of 47 RPs from the large ribosomal subunit (LSU). Ten proteins are partially determined and 14 proteins are missing. Phylogenetic analyses of concatenated RPs from six animals (chaetognath, echinoderm, mammalian, insect, mollusc and sponge) and one fungal taxa do not resolve the chaetognath phylogenetic position, although each mega-sequence comprises approximately 5,000 amino acid residues. This is probably due to the extremely biased base composition and to the high evolutionary rates in chaetognaths. However, the analysis of chaetognath RP genes revealed three unique features in the animal Kingdom. First, whereas generally in animals one RP appeared to have a single type of mRNA, two or more genes are generally transcribed for one RP type in chaetognath. Second, cDNAs with complete 5'-ends encoding a given protein sequence can be divided in two sub-groups according to a short region in their 5'-ends: two novel and highly conserved elements have been identified (5'-TAATTGAGTAGTTT-3' and 5'-TATTAAGTACTAC-3') which could correspond to different transcription factor binding sites on paralog RP genes. And, third, the overall number of deduced paralogous RPs is very high compared to those published for other animals.</p> <p>Conclusion</p> <p>These results suggest that in chaetognaths the deleterious effects of the presence of paralogous RPs, such as apoptosis or cancer are avoided, and also that in each protein family, some of the members could have tissue-specific and extra-ribosomal functions. These results are congruent with the hypotheses of an allopolyploid origin of this phylum and of a ribosome heterogeneity.</p

Reconstruction of full-length 16S rRNA sequences for taxonomic assignment inmetagenomics

National audienceAdvances in the sequencing of uncultured environmental samples, raise a growing need for accurate taxonomic assignment. Accurate identification of organisms present within a community is essential to understanding even the most elementary ecosystems. However, current high-throughput sequencing technologies generate short reads which partially cover full-length marker genes and this poses difficult bioinformatic challenges for taxonomy identification at high resolution. We designed MATAM, a software dedicated to the fast and accurate targeted assembly of short reads sequenced from a genomic marker of interest. The method implements a stepwise process based on construction and analysis of a read overlap graph. It is applied to the assembly of 16S rRNA markers and is validated on simulated, synthetic and genuine metagenomes. We show that MATAM outperforms other available methods in terms of low error rates and recovered genome fractions and is suitable to provide improved assemblies for precise taxonomic assignments

Tunicate mitogenomics and phylogenetics: peculiarities of the Herdmania momus mitochondrial genome and support for the new chordate phylogeny

International audienceBACKGROUND: Tunicates represent a key metazoan group as the sister-group of vertebrates within chordates. The six complete mitochondrial genomes available so far for tunicates have revealed distinctive features. Extensive gene rearrangements and particularly high evolutionary rates have been evidenced with regard to other chordates. This peculiar evolutionary dynamics has hampered the reconstruction of tunicate phylogenetic relationships within chordates based on mitogenomic data. RESULTS: In order to further understand the atypical evolutionary dynamics of the mitochondrial genome of tunicates, we determined the complete sequence of the solitary ascidian Herdmania momus. This genome from a stolidobranch ascidian presents the typical tunicate gene content with 13 protein-coding genes, 2 rRNAs and 24 tRNAs which are all encoded on the same strand. However, it also presents a novel gene arrangement, highlighting the extreme plasticity of gene order observed in tunicate mitochondrial genomes. Probabilistic phylogenetic inferences were conducted on the concatenation of the 13 mitochondrial protein-coding genes from representatives of major metazoan phyla. We show that whereas standard homogeneous amino acid models support an artefactual sister position of tunicates relative to all other bilaterians, the CAT and CAT+BP site- and time-heterogeneous mixture models place tunicates as the sister-group of vertebrates within monophyletic chordates. Moreover, the reference phylogeny indicates that tunicate mitochondrial genomes have experienced a drastic acceleration in their evolutionary rate that equally affects protein-coding and ribosomal-RNA genes. CONCLUSION: This is the first mitogenomic study supporting the new chordate phylogeny revealed by recent phylogenomic analyses. It illustrates the beneficial effects of an increased taxon sampling coupled with the use of more realistic amino acid substitution models for the reconstruction of animal phylogeny

Evidence for the Existence of Elaborate Enzyme Complexes in the Paleoarchean Era

International audience: Due to the lack of macromolecular fossils, the enzymatic repertoire of extinct species has remained largely unknown to date. In an attempt to solve this problem, we have characterized a cyclase subunit (HisF) of the imidazole glycerol phosphate synthase (ImGP-S), which was reconstructed from the era of the last universal common ancestor of cellular organisms (LUCA). As observed for contemporary HisF proteins, the crystal structure of LUCA-HisF adopts the (βα)8-barrel architecture, one of the most ancient folds. Moreover, LUCA-HisF (i) resembles extant HisF proteins with regard to internal 2-fold symmetry, active site residues, and a stabilizing salt bridge cluster, (ii) is thermostable and shows a folding mechanism similar to that of contemporary (βα)8-barrel enzymes, (iii) displays high catalytic activity, and (iv) forms a stable and functional complex with the glutaminase subunit (HisH) of an extant ImGP-S. Furthermore, we show that LUCA-HisF binds to a reconstructed LUCA-HisH protein with high affinity. Our findings suggest that the evolution of highly efficient enzymes and enzyme complexes has already been completed in the LUCA era, which means that sophisticated catalytic concepts such as substrate channeling and allosteric communication existed already 3.5 billion years ago

Cross metathesis for the synthesis of HDAC inhibitors. Potential in multitarget drug design

Histone deacetylases represent a family of eleven zinc-dependant enzymes. Their over expression has been correlated to several human diseases, in particular cancers. The search for compounds able to selectively inhibit one of these HDAC is of high importance to obtain less side effect during treatment as well as avoiding of target effects. In this work we have designed a series of inhibitors using an asymmetric cross metathesis approach. We present the synthesis, some molecular modelling and the biological activities of the prepared compounds.Link ka Knjizi sažetaka se nalazi ovde - http://www.mutalig.eu/2017/06/2nd-annual-meeting-porto-september-21-24-2017