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      Improved annotation of protein-coding genes boundaries in metazoan mitochondrial genomes

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          Abstract

          With the rapid increase of sequenced metazoan mitochondrial genomes, a detailed manual annotation is becoming more and more infeasible. While it is easy to identify the approximate location of protein-coding genes within mitogenomes, the peculiar processing of mitochondrial transcripts, however, makes the determination of precise gene boundaries a surprisingly difficult problem. We have analyzed the properties of annotated start and stop codon positions in detail, and use the inferred patterns to devise a new method for predicting gene boundaries in de novo annotations. Our method benefits from empirically observed prevalances of start/stop codons and gene lengths, and considers the dependence of these features on variations of genetic codes. Albeit not being perfect, our new approach yields a drastic improvement in the accuracy of gene boundaries and upgrades the mitochondrial genome annotation server MITOS to an even more sophisticated tool for fully automatic annotation of metazoan mitochondrial genomes.

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          Abstract The National Center for Biotechnology Information (NCBI) provides a large suite of online resources for biological information and data, including the GenBank® nucleic acid sequence database and the PubMed database of citations and abstracts for published life science journals. The Entrez system provides search and retrieval operations for most of these data from 39 distinct databases. The E-utilities serve as the programming interface for the Entrez system. Augmenting many of the Web applications are custom implementations of the BLAST program optimized to search specialized data sets. New resources released in the past year include PubMed Data Management, RefSeq Functional Elements, genome data download, variation services API, Magic-BLAST, QuickBLASTp, and Identical Protein Groups. Resources that were updated in the past year include the genome data viewer, a human genome resources page, Gene, virus variation, OSIRIS, and PubChem. All of these resources can be accessed through the NCBI home page at www.ncbi.nlm.nih.gov.
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            MitoFish and MitoAnnotator: A Mitochondrial Genome Database of Fish with an Accurate and Automatic Annotation Pipeline

            Mitofish is a database of fish mitochondrial genomes (mitogenomes) that includes powerful and precise de novo annotations for mitogenome sequences. Fish occupy an important position in the evolution of vertebrates and the ecology of the hydrosphere, and mitogenomic sequence data have served as a rich source of information for resolving fish phylogenies and identifying new fish species. The importance of a mitogenomic database continues to grow at a rapid pace as massive amounts of mitogenomic data are generated with the advent of new sequencing technologies. A severe bottleneck seems likely to occur with regard to mitogenome annotation because of the overwhelming pace of data accumulation and the intrinsic difficulties in annotating sequences with degenerating transfer RNA structures, divergent start/stop codons of the coding elements, and the overlapping of adjacent elements. To ease this data backlog, we developed an annotation pipeline named MitoAnnotator. MitoAnnotator automatically annotates a fish mitogenome with a high degree of accuracy in approximately 5 min; thus, it is readily applicable to data sets of dozens of sequences. MitoFish also contains re-annotations of previously sequenced fish mitogenomes, enabling researchers to refer to them when they find annotations that are likely to be erroneous or while conducting comparative mitogenomic analyses. For users who need more information on the taxonomy, habitats, phenotypes, or life cycles of fish, MitoFish provides links to related databases. MitoFish and MitoAnnotator are freely available at http://mitofish.aori.u-tokyo.ac.jp/ (last accessed August 28, 2013); all of the data can be batch downloaded, and the annotation pipeline can be used via a web interface.
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              Improved systematic tRNA gene annotation allows new insights into the evolution of mitochondrial tRNA structures and into the mechanisms of mitochondrial genome rearrangements

              Transfer RNAs (tRNAs) are present in all types of cells as well as in organelles. tRNAs of animal mitochondria show a low level of primary sequence conservation and exhibit ‘bizarre’ secondary structures, lacking complete domains of the common cloverleaf. Such sequences are hard to detect and hence frequently missed in computational analyses and mitochondrial genome annotation. Here, we introduce an automatic annotation procedure for mitochondrial tRNA genes in Metazoa based on sequence and structural information in manually curated covariance models. The method, applied to re-annotate 1876 available metazoan mitochondrial RefSeq genomes, allows to distinguish between remaining functional genes and degrading ‘pseudogenes’, even at early stages of divergence. The subsequent analysis of a comprehensive set of mitochondrial tRNA genes gives new insights into the evolution of structures of mitochondrial tRNA sequences as well as into the mechanisms of genome rearrangements. We find frequent losses of tRNA genes concentrated in basal Metazoa, frequent independent losses of individual parts of tRNA genes, particularly in Arthropoda, and wide-spread conserved overlaps of tRNAs in opposite reading direction. Direct evidence for several recent Tandem Duplication-Random Loss events is gained, demonstrating that this mechanism has an impact on the appearance of new mitochondrial gene orders.
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                Author and article information

                Journal
                Nucleic Acids Res
                Nucleic Acids Res
                nar
                Nucleic Acids Research
                Oxford University Press
                0305-1048
                1362-4962
                18 November 2019
                04 October 2019
                04 October 2019
                : 47
                : 20
                : 10543-10552
                Affiliations
                [1 ] Center for Molecular Biodiversity Research (ZMB), Zoological Research Museum Alexander Koenig (ZFMK) , Adenauerallee 160, D-53113 Bonn, Germany
                [2 ] Inserm, U1110, Institut de Recherche sur les Maladies Virales et Hépatiques , 3 Rue Koeberlé, F-67000 Strasbourg, France
                [3 ] Université de Strasbourg , 4 Rue Blaise Pascal, F-67081 Strasbourg, France
                [4 ] Bioinformatics, Department of Computer Science, Universität Leipzig , Härtelstraße 16-18, D-04107 Leipzig, Germany
                [5 ] Doctoral School of Science and Technology, AZM Center for Biotechnology Research, Lebanese University , Tripoli, Lebanon
                [6 ] Interdisciplinary Center for Bioinformatics, University of Leipzig , Härtelstraße 16-18, D-04107 Leipzig, Germany
                [7 ] Competence Center for Scalable Data Services and Solutions Dresden/Leipzig, German Centre for Integrative Biodiversity Research (iDiv), and Leipzig Research Center for Civilization Diseases, Universität Leipzig , Leipzig, Germany
                [8 ] Max Planck Institute for Mathematics in the Sciences , Inselstraße 22, D-04103 Leipzig, Germany
                [9 ] Fraunhofer Institut for Cell Therapy and Immunology , Perlickstraße 1, D-04103 Leipzig, Germany
                [10 ] Department of Theoretical Chemistry, University of Vienna , Währingerstraße 17, A-1090 Wien, Austria
                [11 ] Santa Fe Institute , 1399 Hyde Park Rd., Santa Fe, NM 87501, USA
                [12 ] Swarm Intelligence and Complex Systems, Department of Computer Science, Universität Leipzig , Augustusplatz 10, D-04109 Leipzig, Germany
                [13 ] Helmholtz Centre for Environmental Research – UFZ , Young Investigators Group Bioinformatics and Transcriptomics Permoserstraße 15, D-04318 Leipzig, Germany
                Author notes
                To whom correspondence should be addressed. Tel: +49 341 235482296; Fax: +49 342 2351561; Email: m.bernt@ 123456ufz.de
                Author information
                http://orcid.org/0000-0001-5618-0547
                http://orcid.org/0000-0002-5426-1092
                Article
                gkz833
                10.1093/nar/gkz833
                6847864
                31584075
                65d981eb-83d9-4e8b-97c5-e0816da5a1db
                © The Author(s) 2019. Published by Oxford University Press on behalf of Nucleic Acids Research.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 September 2019
                : 30 August 2019
                : 06 October 2018
                Page count
                Pages: 10
                Funding
                Funded by: University of Leipzig
                Categories
                Computational Biology

                Genetics
                Genetics

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