Control of growth and gut maturation by HoxD genes and the associated lncRNA Haglr.

During embryonic development, Hox genes participate in the building of a functional digestive system in metazoans, and genetic conditions involving these genes lead to important, sometimes lethal, growth retardation. Recently, this phenotype was obtained after deletion of Haglr, the Hoxd antisense growth-associated long noncoding RNA (lncRNA) located between Hoxd1 and Hoxd3 In this study, we have analyzed the function of Hoxd genes in delayed growth trajectories by looking at several nested targeted deficiencies of the mouse HoxD cluster. Mutant pups were severely stunted during the suckling period, but many recovered after weaning. After comparing seven distinct HoxD alleles, including CRISPR/Cas9 deletions involving Haglr, we identified Hoxd3 as the critical component for the gut to maintain milk-digestive competence. This essential function could be abrogated by the dominant-negative effect of HOXD10 as shown by a genetic rescue approach, thus further illustrating the importance of posterior prevalence in Hox gene function. A role for the lncRNA Haglr in the control of postnatal growth could not be corroborated

Phylogenomics and Genome Annotation

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Repository/R-Forge/DateTimeStamp 2012-12-11 16:03:18

Suggests ade4, segmented Description Exploratory data analysis and data visualization for biological sequence (DNA and protein) data. Include also utilities for sequence data management under the ACNUC system. License GPL (> = 2

Ori-Finder: A web-based system for finding oriCs in unannotated bacterial genomes

<p>Abstract</p> <p>Background</p> <p>Chromosomal replication is the central event in the bacterial cell cycle. Identification of replication origins (<it>oriC</it>s) is necessary for almost all newly sequenced bacterial genomes. Given the increasing pace of genome sequencing, the current available software for predicting <it>oriC</it>s, however, still leaves much to be desired. Therefore, the increasing availability of genome sequences calls for improved software to identify <it>oriC</it>s in newly sequenced and unannotated bacterial genomes.</p> <p>Results</p> <p>We have developed Ori-Finder, an online system for finding <it>oriC</it>s in bacterial genomes based on an integrated method comprising the analysis of base composition asymmetry using the <it>Z</it>-curve method, distribution of DnaA boxes, and the occurrence of genes frequently close to <it>oriC</it>s. The program can also deal with unannotated genome sequences by integrating the gene-finding program ZCURVE 1.02. Output of the predicted results is exported to an HTML report, which offers convenient views on the results in both graphical and tabular formats.</p> <p>Conclusion</p> <p>A web-based system to predict replication origins of bacterial genomes has been presented here. Based on this system, <it>oriC </it>regions have been predicted for the bacterial genomes available in GenBank currently. It is hoped that Ori-Finder will become a useful tool for the identification and analysis of <it>oriC</it>s in both bacterial and archaeal genomes.</p

CpG Islands: Starting Blocks for Replication and Transcription

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Domestic chickens activate a piRNA defense against avian leukosis virus

PIWI-interacting RNAs (piRNAs) protect the germ line by targeting transposable elements (TEs) through the base-pair complementarity. We do not know how piRNAs co-evolve with TEs in chickens. Here we reported that all active TEs in the chicken germ line are targeted by piRNAs, and as TEs lose their activity, the corresponding piRNAs erode away. We observed de novo piRNA birth as host responds to a recent retroviral invasion. Avian leukosis virus (ALV) has endogenized prior to chicken domestication, remains infectious, and threatens poultry industry. Domestic fowl produce piRNAs targeting ALV from one ALV provirus that was known to render its host ALV resistant. This proviral locus does not produce piRNAs in undomesticated wild chickens. Our findings uncover rapid piRNA evolution reflecting contemporary TE activity, identify a new piRNA acquisition modality by activating a pre-existing genomic locus, and extend piRNA defense roles to include the period when endogenous retroviruses are still infectious. DOI: http://dx.doi.org/10.7554/eLife.24695.00

Long-Range Bidirectional Strand Asymmetries Originate at CpG Islands in the Human Genome

In the human genome, CpG islands (CGIs), which are GC- and CpG-rich sequences, are associated with transcription starting sites (TSSs); in addition, there is evidence that CGIs harbor origins of bidirectional replication (OBRs) and are preferred sites for heteroduplex formation during recombination. Transcription, replication, and recombination processes are known to induce specific mutational patterns in various genomes, and therefore, these patterns are expected to be found around CGIs. We use triple alignments of human, chimp, and macaque to compute the rates of nucleotide substitutions in up to 1 Mbps long intergenic regions on both sides of CGIs. Our analysis revealed that around a CGI there is an asymmetry between complementary substitution rates that is similar to the one that found around the OBR in bacteria. We hypothesize that these asymmetries are induced by differences in the replication of the leading and lagging strand and that a significant number of CGIs overlap OBRs. Within CGIs, we observed a mutational signature of GC-biased gene conversion that is associated with recombination. We suggest that recombination has played a major role in the creation of CGIs

Anatomy of protein disorder, flexibility and disease-related mutations.

Integration of protein structural information with human genetic variation and pathogenic mutations is essential to understand molecular mechanisms associated with the effects of polymorphisms on protein interactions and cellular processes. We investigate occurrences of non-synonymous SNPs in ordered and disordered protein regions by systematic mapping of common variants and disease-related SNPs onto these regions. We show that common variants accumulate in disordered regions; conversely pathogenic variants are significantly depleted in disordered regions. These different occurrences of pathogenic and common SNPs can be attributed to a negative selection on random mutations in structurally highly constrained regions. New approaches in the study of quantitative effects of pathogenic-related mutations should effectively account for all the possible contexts and relative functional constraints in which the sequence variation occurs.This research was supported by the Biotechnology and Biological Sciences Research Council (BB/H018409/1 to FF), the British Heart Foundation (FS/12/41/29724 to AF and FF) and the Leukaemia & Lymphoma Research (to FF). SSC is funded by a Leukaemia & Lymphoma Research Gordon Piller PhD Studentship

Assessing Recent Selection and Functionality at Long Non-Coding RNA Loci in the Mouse Genome

This work was supported by the Biotechnology and Biological Sciences Research Council and The Wellcome Trust. A.N. was supported by the Swiss National Science Foundation (Grant: PZ00P3_142636). H.K. was supported by the European Research Council Starting (Grant: 242597, SexGenTransEvolution) and the Swiss National Science Foundation (Grants: 130287 and 146474).Long noncoding RNAs (lncRNAs) are one of the most intensively studied groups of noncoding elements. Debate continues over what proportion of lncRNAs are functional or merely represent transcriptional noise. Although characterization of individual lncRNAs has identified approximately 200 functional loci across the Eukarya, general surveys have found only modest or no evidence of long-term evolutionary conservation. Although this lack of conservation suggests that most lncRNAs are nonfunctional, the possibility remains that some represent recent evolutionary innovations. We examine recent selection pressures acting on lncRNAs in mouse populations. We compare patterns of within-species nucleotide variation at approximately 10,000 lncRNA loci in a cohort of the wild house mouse, Mus musculus castaneus, with between-species nucleotide divergence from the rat (Rattus norvegicus). Loci under selective constraint are expected to show reduced nucleotide diversity and divergence. We find limited evidence of sequence conservation compared with putatively neutrally evolving ancestral repeats (ARs). Comparisons of sequence diversity and divergence between ARs, protein-coding (PC) exons and lncRNAs, and the associated flanking regions, show weak, but significantly lower levels of sequence diversity and divergence at lncRNAs compared with ARs. lncRNAs conserved deep in the vertebrate phylogeny show lower within-species sequence diversity than lncRNAs in general. A set of 74 functionally characterized lncRNAs show levels of diversity and divergence comparable to PC exons, suggesting that these lncRNAs are under substantial selective constraints. Our results suggest that, in mouse populations, most lncRNA loci evolve at rates similar to ARs, whereas older lncRNAs tend to show signals of selection similar to PC genes.PostprintPeer reviewe