The Newick utilities: high-throughput phylogenetic tree processing in the Unix shell

Summary: We present a suite of Unix shell programs for processing any number of phylogenetic trees of any size. They perform frequently-used tree operations without requiring user interaction. They also allow tree drawing as scalable vector graphics (SVG), suitable for high-quality presentations and further editing, and as ASCII graphics for command-line inspection. As an example we include an implementation of bootscanning, a procedure for finding recombination breakpoints in viral genomes. Availability: C source code, Python bindings and executables for various platforms are available from http://cegg.unige.ch/newick_utils. The distribution includes a manual and example data. The package is distributed under the BSD License. Contact: [email protected]

miRmap: Comprehensive prediction of microRNA target repression strength

MicroRNAs, or miRNAs, post-transcriptionally repress the expression of protein-coding genes. The human genome encodes over 1000 miRNA genes that collectively target the majority of messenger RNAs (mRNAs). Base pairing of the so-called miRNA ‘seed' region with mRNAs identifies many thousands of putative targets. Evaluating the strength of the resulting mRNA repression remains challenging, but is essential for a biologically informative ranking of potential miRNA targets. To address these challenges, predictors may use thermodynamic, evolutionary, probabilistic or sequence-based features. We developed an open-source software library, miRmap, which for the first time comprehensively covers all four approaches using 11 predictor features, 3 of which are novel. This allowed us to examine feature correlations and to compare their predictive power in an unbiased way using high-throughput experimental data from immunopurification, transcriptomics, proteomics and polysome fractionation experiments. Overall, target site accessibility appears to be the most predictive feature. Our novel feature based on PhyloP, which evaluates the significance of negative selection, is the best performing predictor in the evolutionary category. We combined all the features into an integrated model that almost doubles the predictive power of TargetScan. miRmap is freely available from http://cegg.unige.ch/mirma

A remarkably stable TipE gene cluster: evolution of insect Para sodium channel auxiliary subunits

<p>Abstract</p> <p>Background</p> <p>First identified in fruit flies with temperature-sensitive paralysis phenotypes, the <it>Drosophila melanogaster TipE </it>locus encodes four voltage-gated sodium (Na_V) channel auxiliary subunits. This cluster of <it>TipE</it>-like genes on chromosome 3L, and a fifth family member on chromosome 3R, are important for the optional expression and functionality of the Para Na_Vchannel but appear quite distinct from auxiliary subunits in vertebrates. Here, we exploited available arthropod genomic resources to trace the origin of <it>TipE</it>-like genes by mapping their evolutionary histories and examining their genomic architectures.</p> <p>Results</p> <p>We identified a remarkably conserved synteny block of <it>TipE</it>-like orthologues with well-maintained local gene arrangements from 21 insect species. Homologues in the water flea, <it>Daphnia pulex</it>, suggest an ancestral pancrustacean repertoire of four <it>TipE</it>-like genes; a subsequent gene duplication may have generated functional redundancy allowing gene losses in the silk moth and mosquitoes. Intronic nesting of the insect <it>TipE </it>gene cluster probably occurred following the divergence from crustaceans, but in the flour beetle and silk moth genomes the clusters apparently escaped from nesting. Across Pancrustacea, <it>TipE </it>gene family members have experienced intronic nesting, escape from nesting, retrotransposition, translocation, and gene loss events while generally maintaining their local gene neighbourhoods. <it>D. melanogaster TipE</it>-like genes exhibit coordinated spatial and temporal regulation of expression distinct from their host gene but well-correlated with their regulatory target, the Para Na_Vchannel, suggesting that functional constraints may preserve the <it>TipE </it>gene cluster. We identified homology between TipE-like Na_Vchannel regulators and vertebrate Slo-beta auxiliary subunits of big-conductance calcium-activated potassium (BK_Ca) channels, which suggests that ion channel regulatory partners have evolved distinct lineage-specific characteristics.</p> <p>Conclusions</p> <p><it>TipE</it>-like genes form a remarkably conserved genomic cluster across all examined insect genomes. This study reveals likely structural and functional constraints on the genomic evolution of insect <it>TipE </it>gene family members maintained in synteny over hundreds of millions of years of evolution. The likely common origin of these Na_Vchannel regulators with BK_Caauxiliary subunits highlights the evolutionary plasticity of ion channel regulatory mechanisms.</p

miRmap web: comprehensive microRNA target prediction online

MicroRNAs (miRNAs) posttranscriptionally repress the expression of protein-coding genes. Based on the partial complementarity between miRNA and messenger RNA pairs with a mandatory so-called ‘seed' sequence, many thousands of potential targets can be identified. Our open-source software library, miRmap, ranks these potential targets with a biologically meaningful criterion, the repression strength. MiRmap combines thermodynamic, evolutionary, probabilistic and sequence-based features, which cover features from TargetScan, PITA, PACMIT and miRanda. Our miRmap web application offers a user-friendly and feature-rich resource for browsing precomputed miRNA target predictions for model organisms, as well as for predicting and ranking targets for user-submitted sequences. MiRmap web integrates sorting, filtering and exporting of results from multiple queries, as well as providing programmatic access, and is available at http://mirmap.ezlab.or

OrthoDB: the hierarchical catalog of eukaryotic orthologs

The concept of orthology is widely used to relate genes across different species using comparative genomics, and it provides the basis for inferring gene function. Here we present the web accessible OrthoDB database that catalogs groups of orthologous genes in a hierarchical manner, at each radiation of the species phylogeny, from more general groups to more fine-grained delineations between closely related species. We used a COG-like and Inparanoid-like ortholog delineation procedure on the basis of all-against-all Smith-Waterman sequence comparisons to analyze 58 eukaryotic genomes, focusing on vertebrates, insects and fungi to facilitate further comparative studies. The database is freely available at http://cegg.unige.ch/orthod

Expression profiles of urbilaterian genes uniquely shared between honey bee and vertebrates

<p>Abstract</p> <p>Background</p> <p>Large-scale comparison of metazoan genomes has revealed that a significant fraction of genes of the last common ancestor of Bilateria (Urbilateria) is lost in each animal lineage. This event could be one of the underlying mechanisms involved in generating metazoan diversity. However, the present functions of these ancient genes have not been addressed extensively. To understand the functions and evolutionary mechanisms of such ancient Urbilaterian genes, we carried out comprehensive expression profile analysis of genes shared between vertebrates and honey bees but not with the other sequenced ecdysozoan genomes (honey bee-vertebrate specific, HVS genes) as a model.</p> <p>Results</p> <p>We identified 30 honey bee and 55 mouse HVS genes. Many HVS genes exhibited tissue-selective expression patterns; intriguingly, the expression of 60% of honey bee HVS genes was found to be brain enriched, and 24% of mouse HVS genes were highly expressed in either or both the brain and testis. Moreover, a minimum of 38% of mouse HVS genes demonstrated neuron-enriched expression patterns, and 62% of them exhibited expression in selective brain areas, particularly the forebrain and cerebellum. Furthermore, gene ontology (GO) analysis of HVS genes predicted that 35% of genes are associated with DNA transcription and RNA processing.</p> <p>Conclusion</p> <p>These results suggest that HVS genes include genes that are biased towards expression in the brain and gonads. They also demonstrate that at least some of Urbilaterian genes retained in the specific animal lineage may be selectively maintained to support the species-specific phenotypes.</p

OrthoDB: a hierarchical catalog of animal, fungal and bacterial orthologs

The concept of orthology provides a foundation for formulating hypotheses on gene and genome evolution, and thus forms the cornerstone of comparative genomics, phylogenomics and metagenomics. We present the update of OrthoDB—the hierarchical catalog of orthologs (http://www.orthodb.org). From its conception, OrthoDB promoted delineation of orthologs at varying resolution by explicitly referring to the hierarchy of species radiations, now also adopted by other resources. The current release provides comprehensive coverage of animals and fungi representing 252 eukaryotic species, and is now extended to prokaryotes with the inclusion of 1115 bacteria. Functional annotations of orthologous groups are provided through mapping to InterPro, GO, OMIM and model organism phenotypes, with cross-references to major resources including UniProt, NCBI and FlyBase. Uniquely, OrthoDB provides computed evolutionary traits of orthologs, such as gene duplicability and loss profiles, divergence rates, sibling groups, and now extended with exon-intron architectures, syntenic orthologs and parent-child trees. The interactive web interface allows navigation along the species phylogenies, complex queries with various identifiers, annotation keywords and phrases, as well as with gene copy-number profiles and sequence homology searches. With the explosive growth of available data, OrthoDB also provides mapping of newly sequenced genomes and transcriptomes to the current orthologous group

OrthoDB: the hierarchical catalog of eukaryotic orthologs in 2011

The concept of homology drives speculation on a gene's function in any given species when its biological roles in other species are characterized. With reference to a specific species radiation homologous relations define orthologs, i.e. descendants from a single gene of the ancestor. The large-scale delineation of gene genealogies is a challenging task, and the numerous approaches to the problem reflect the importance of the concept of orthology as a cornerstone for comparative studies. Here, we present the updated OrthoDB catalog of eukaryotic orthologs delineated at each radiation of the species phylogeny in an explicitly hierarchical manner of over 100 species of vertebrates, arthropods and fungi (including the metazoa level). New database features include functional annotations, and quantification of evolutionary divergence and relations among orthologous groups. The interface features extended phyletic profile querying and enhanced text-based searches. The ever-increasing sampling of sequenced eukaryotic genomes brings a clearer account of the majority of gene genealogies that will facilitate informed hypotheses of gene function in newly sequenced genomes. Furthermore, uniform analysis across lineages as different as vertebrates, arthropods and fungi with divergence levels varying from several to hundreds of millions of years will provide essential data for uncovering and quantifying long-term trends of gene evolution. OrthoDB is freely accessible from http://cegg.unige.ch/orthod

miROrtho: computational survey of microRNA genes

MicroRNAs (miRNAs) are short, non-protein coding RNAs that direct the widespread phenomenon of post-transcriptional regulation of metazoan genes. The mature ∼22-nt long RNA molecules are processed from genome-encoded stem-loop structured precursor genes. Hundreds of such genes have been experimentally validated in vertebrate genomes, yet their discovery remains challenging, and substantially higher numbers have been estimated. The miROrtho database (http://cegg.unige.ch/mirortho) presents the results of a comprehensive computational survey of miRNA gene candidates across the majority of sequenced metazoan genomes. We designed and applied a three-tier analysis pipeline: (i) an SVM-based ab initio screen for potent hairpins, plus homologs of known miRNAs, (ii) an orthology delineation procedure and (iii) an SVM-based classifier of the ortholog multiple sequence alignments. The web interface provides direct access to putative miRNA annotations, ortholog multiple alignments, RNA secondary structure conservation, and sequence data. The miROrtho data are conceptually complementary to the miRBase catalog of experimentally verified miRNA sequences, providing a consistent comparative genomics perspective as well as identifying many novel miRNA genes with strong evolutionary suppor

Protein coding potential of retroviruses and other transposable elements in vertebrate genomes

We suggest an annotation strategy for genes encoded by retroviruses and transposable elements (RETRA genes) based on a set of marker protein domains. Usually RETRA genes are masked in vertebrate genomes prior to the application of automated gene prediction pipelines under the assumption that they provide no selective advantage to the host. Yet, we show that about 1000 genes in four vertebrate gene sets analyzed contain at least one RETRA gene marker domain. Using the conservation of genomic neighborhood (synteny), we were able to discriminate between RETRA genes with putative functionality in the vertebrates and those that probably function only in the context of mobile elements. We identified 35 such genes in human, along with their corresponding mouse and rat orthologs; which included almost all known human genes with similarity to mobile elements. The results also imply that the vast majority of the remaining RETRA genes in current gene sets are unlikely to encode vertebrate functions. To automatically annotate RETRA genes in other vertebrate genomes, we provide as a tool a set of marker protein domains and a manually refined list of domesticated or ancestral RETRA genes for rescuing genes with vertebrate functions