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MitoRes  is an update of the MitoNuc database , extensively modified in its structure, data sources and graphical interface. MitoRes has been developed with the aim to provide a comprehensive, integrated and non-redundant resource for functional and comparative studies supporting research on basic science of mitochondria. The database contains data on nuclear-encoded mitochondrial proteins in Metazoa and provides comprehensive sequence datasets (gene, transcript and protein) as well as useful tools for their extraction and export. In addition, MitoRes clusters proteins on the basis of their sequence similarity and interconnects them with genomic data. A search engine and sequence management tools allow the query/retrieval of the database content and the extraction and export of sequences and related sub-sequences (intron, exon, UTR, CDS, signal peptide and gene flanking regions) ready to be used for in silico analysis.
Recent develoments :
Changes recently introduced with respect to the last published version of the MitoNuc database have concerned (1) database structure, (2) data sources, (3) database content, (4) updating procedures (5) Web interface and (6) query/retrieval tool. More details are provided in the on-line Manual accessible by the database Home page.
This work has been supported by 'Ministero dell’Istruzione, dell’Università e della Ricerca’ (MIUR), Italy, within the grants of PNR 2001-2003 (FIRB art.8) D.M. 199, Strategic Program: Post-genome, grant 31-063933; FIRB 2003 art. 8 D.D. 2187 del 12-12-2003 LIBI.
1. Catalano D, Licciulli F, Turi A, Grillo G, Saccone C, D'Elia D. MitoRes: a resource of nuclear-encoded mitochondrial genes and their products in Metazoa. BMC Bioinformatics, 2006 7:36
2. Attimonelli M, Catalano D, Gissi C, Grillo G, Licciulli F, Liuni S, Santamaria M, Pesole G, Saccone C. MitoNuc: a database of nuclear genes coding for mitochondrial proteins. Update 2002. Nucleic Acids Res. 2002, 30: 172-173
HmtDB is a well-integrated web-based human mitochondrial bioinformatics resource aimed at supporting population genetics and mitochondrial disease studies, thanks to a new approach based on site-specific nucleotide and aminoacid variability estimation (Attimonelli et al. 2005). HmtDB consists of a database of Human Mitochondrial Genomes, annotated with population data, and a set of bioinformatics tools, able to produce site-specific variability data and to automatically characterize newly sequenced human mitochondrial genomes. HmtDB is structured in five macro-functions: "Query", "Analyze your genome", "Submission", "HmtDB downloading" and "Session Query History", available from the Menu page. The Query page allows the users to draw data from HmtDB, through a multi criterion form made up of pop-up menus and free text retrieval windows. The Analyze your genome function can be used to automatically characterize a mitochondrial sequence. Through the Submission page the users can submit a new human mitochondrial genome. HmtDB downloading allows the researchers to view and download multi-aligned sequence data and site-specific nucleotide variability data, both regarding the entire database, continent specific and patient subsets. Intra-human and inter-species aminoacid variability data estimated on the 13 coding for proteins genes of the available human genomes and 60 mammalian species are also available. Thanks to the existence of Session Query History, the users can view the history of previously performed analyses. The current release of HmtDB provides access to variability and sequence data of 2879 human mitochondrial genomes from normal subjects and 609 from subjects with clinical phenotype (update September 2007). The human mitochondrial genomes in HmtDB are fully annotated with information about sample: ethnic origin, age, phenotype of the subject and tissue. HmtDB is freely available at http://www.hmdb.uniba.it. The HmtDB project has contributed to complete and/or refine human mitochondrial haplogroup classification on the basis of variability estimation. Indeed, variability the nucleotidic mitochondrial sites, presenting discriminating variability values estimated to the continent-specific datasets compared to the rest of the world, can be considered good population markers (Accetturo et al.2006). From a clinical point of view, site-specific variability values could help to understand the real pathogenic potential of mitochondrial mutations. Indeed, high nucleotidic and aminoacidic variability values inter- and intra-species are indicative of low functional constraints in the region presenting them.
This work was supported by the "Ministero Università e Ricerca Scientifica", Italy (PRIN2003; Progetto MURST Cluster C03/2000, CEGBA), MIUR - Functional Genomics and by a fund from ESF (P.O.P. 2000-2006). Accetturo M. was supported by a fellowship and fund from ESF (P.O.P. 2000–2006). We thank Prof. Antonio Torroni of the Dept. of Genetics and Microbiology of the University of Pavia, for his invaluable support and advice regarding human mtDNA haplogroup classification.
1. Attimonelli M, Accetturo M, Santamaria M, Lascaro D, Scioscia G, Pappadà G, Russo L, Zanchetta L, Tommaseo-Ponzetta M. (2005) HmtDB, a Human Mitochondrial Genomic Resource Based on Variability Studies Supporting Population Genetics and Biomedical Research. BMC Bioinformatics, 6(4):S4.
2. Accetturo M, Santamaria M, Lascaro D, Rubino F, Achilli A, Torroni A, Tommaseo-Ponzetta M, Attimonelli M. (2006) Human mtDNA Site-Specific Variability Values Can Act as Haplogroup Markers. Human Mutation 27(9), 965-974.
Comparative analysis of metazoan mitochondrial genomes
GenDecoder is a prediction server for animal mitochondrial genetic codes. It provides information about codon-usage, amino acid composition, GC content and a final genetic code prediction for a mitochondrial genome sequence.
MITOPRED uses Pfam domains, pI values and amino acid composition to predict nuclear-encoded mitochondrial proteins. Predictions have been precomputed for a number of proteomes, as well as for all Eukaryotic sequences in Swiss-Prot and TrEMBL. Users may directly enter or upload a file with a list of protein sequences or Swiss-Prot/TrEMBL accession numbers.
OGRe is a relational database containing information on completely sequenced animal mitochondrial genomes. It currently contains 473 species. This is the full set of complete metazoan mitochondrial genomes available as of July 2004. The structure of OGRe is based on a taxonomic classification of species that allows easy retrieval of information from related groups of species. OGRe allows the 'one-click’ retrieval of any selected set of mitochondrial genes from any selected set of species. OGRe provides several ways of visualizing information on gene order and genome rearrangements. Diagrams illustrating the genome arrangement can be automatically generated for any selected set of species from the information in the database. Diagrams for pair-wise comparison of species show the positions of breakpoints in the gene order and clearly highlight the sections of the genome that have moved. A listing of all distinct gene orders in the database is given, and distance matrices using breakpoint and inversion distances are provided. The system displays information on the frequencies of bases, amino acids and codons in mitochondrial genes and a graphical presentation of this information is possible. Full codon usage tables can also be downloaded for these genomes.
This database is dedicated to the nuclear genes specifying the enzymes, structural proteins, and other proteins, many still not identified, involved in mitochondrial biogenesis and function. MitoDat highlights predominantly human nuclear-encoded mitochondrial proteins, although we are including proteins from other animals in addition to those currently known only from yeast and other fungal mitochondria, as well as from plant mitochondria. The database consolidates information from various biological databases, eg., GenBank, SwissPro, Genome Data Base (GDB), Online Mendelian Inheritance in Man (OMIM), et al. Because the mitochondrion has a central role in cellular metabolism, it is involved in many human diseases. This database should help us in studying these diseases. We are also hyperlinked to the Report of the committee on human mitochondrial DNA, maintained by the Wallace group at Emory (http://infinity.gen.emory.edu/mitomap.html). It can be accessed here and also from the results when searching mitoDat for mitochondrially encoded genes. The Report of the committee on human mitochondrial DNA is currently the most comprehensive source of information on mitochondrial DNA mutations, other defects, and disorders in which the mitochondrial DNA deficiencies have been associated.
Experimentally identified mitochondrial proteins in Arabidopsis
1. Heazlewood JL, Tonti-Filippini JS, Gout A, Day DA, Whelan J and Millar AH (2004) Experimental analysis of the Arabidopsis mitochondrial proteome highlights signalling and regulatory components, provides assessment of targeting prediction programs and points to plant specific mitochondrial proteins. Plant Cell 16: 241-256.
MitoNuc is a specialized database of nuclear encoded mitochondrial proteins in Metazoa. It has been developed with the aim to provide a comprehensive, integrated and non-redundant resource for functional and comparative genomic
studies supporting research on basic science of mitochondria and mitochondrial pathogenesis. To
this purpose the database integrates information from the most accredited world-wide databases
to bring together information on genes, transcripts and encoded proteins and provides the users
with a query/retrieval tool allowing the extraction of genomic and protein sequences and sub-
sequences. Each database entry consists of a nuclear gene encoding for a mitochondrial protein
in a given species, and, besides bio-sequences data, it reports information on: species name and
taxonomic classification, gene name, functional product, sub-cellular localization, protein
tissue specificity, Enzyme Classification (EC) code, gene and transcript maps. For each gene and
gene product the Gene Ontology (GO) classification with regard to molecular function, biological
processes and cellular component is reported too.
The database is retrievable via Web
interface at the following address: http://www2.ba.itb.cnr.it/mitonuc/. It is also
generated in a flat file format, EMBL-like, available at our SRS site (http://www.ba.itb.cnr.it/srs/). Both the database
versions allow the extraction of sequences and sub-sequences (gene, intron, exon, mRNA, 5'
and 3'UTRs, CDS, signal peptides, protein) and the cross-linking to other databases
(ENSEMBL, RefSeq, UTRdb, SwissProt, GO, OMIM, EMBL).
Our collection provides sequences from hypervariable regions I and II (HVR I and HVR II) as well as complete mitochondrial DNA together with related information on individuals such as original reference, country of origin, population and language affiliation. At the moment the HvrBase contains data from 10240 individual (9768 humans, 469 great apes and 3 neanderthaler). The current state of the database is listed at www.hvrbase.org/stat.html and includes a detailed statistic on the dataset. The continous growth of the database is guaranteed by permanent updates. All data is stored in a relational database which offers a variety of different queries. The query conditions can be choosen on a user-friendly webinterface which involves many options for the output format. We tried to design the query formular to be self-explanatory but in any case you will find an online help on the webpage.
Recent develoments :
According to the previous version the innovations are: - The HvrBase is located on its own domains: www.hvrbase.de www.hvrbase.org As the old URL will not be supported in the future you should change your bookmarks. - It is possible now to exclude data sets from the result if the sequences admits '?' or 'N' (see the paraphernalia section on the formular). - The new version offers complete mitochondrial data. For these datasets a query formular with similar functionalities as for HVR I and HVR II is in progress. It is also planned to include population data from nuclear loci, like Xq13.3, ZFX and ZFY-introns, beta-globin, lpl and other. The query formular is improved continously in design and functionalities, e.g. region specific data access via interactive maps is under development.
We gratefully acknowledge financial support from the DFG and thank all colleagues who provided their sequence data and gave additional information when needed.
1. Handt,O.,Meyer,S.and von Haeseler,A. (1998) Compilation of human mtDNA control region sequences. Nucleic Acids Res.,26,126-129.
2. Burckhardt, F., von Haeseler, A. and Meyer, S.(1999) HvrBase:compilation of mtDNA control region sequences from primates. Nucleic Acids Res.,27,138-142.
3. Meyer, S., Rupp, K., von Haeseler, A. and Radtke, A. (2001) HvrBase: database of primate mtDNA control region sequences. In: The Molecular Biology Database Collection: an updated compilation of biological database resources (Baxevanis, A., ed.) Nucleic Acids Research 29(1):1-10
PLMItRNA is a database developed to facilitate retrieval of information on the distribution of tRNA molecules and genes in mitochondria of green plants (higher plants and green algae) and Cryptophyta, Rhodophyta and Stramenopiles algae. Currently PLMItRNA contains 615 entries for 581 genes and 34 tRNA sequences identified among 27 higher plants, ten green algae, one Cryptophyta, four red algae (Rhodophyta) and two Stramenopiles. Last updating has been realised in July 2002, by SRS and FastA analysis of the EMBL database [G. Rainaldi et al., 2003 Database Issue of Nucleic Acids Research]. A complete description of the database can also be found at the PLMItRNA site: http://bighost.area.ba .cnr.it/PLMItRNA/
Recent develoments :
A table of promoter sequences identified, or deduced from sequence analysis, for tRNA genes in the mitochondrial genomes of Angiospermae (Flowering plants) is available in the PLMItRNA database.
1. Damiano, F., Gallerani, R., Liuni, S., Licciulli, F. and Ceci, L.R. (2001) PLMItRNA, a database for mitochondrial tRNA genes and tRNAs in photosynthetic eukaryotes. Nucleic Acids Res., 29, 167-168.
2. Knoop, V. and Brennicke, A. (2002) Molecular Biology of the Plant Mitochondrion. Critical Reviews in Plant Sciences, 21: 111-126.
Human mitochondrial protein database
The mitochondrial genome, contained in the subcellular mitochondrial network, encodes a small number of peptides pivotal for cellular energy production. Mitochondrial genes are highly polymorphic and cataloguing existing variation is of interest for medical scientists involved in the identification of mutations causing mitochondrial dysfunction, as well as for population genetics studies. mtDB has provided a comprehensive database of complete human mitochondrial genomes since early 2000. At this time, due to an increase in the number of published complete human mitochondrial genome sequences, it became necessary to provide a web-based database of human whole genome and complete coding region sequences. As of August 2005 this database contains 2104 sequences (1544 complete genome and 560 coding region) available to download or search for specific polymorphisms. Of special interest to medical researchers and population geneticists evaluating specific positions is a complete list of (currently 3311) mitochondrial polymorphisms among these sequences. Recent expansions in the capabilities of mtDB include a haplotype search function and the ability to identify and download sequences carrying particular variants.
MamMibase, the Mammalian Mitochondrial Genome Database, is a relational database of complete mitochondrial genome sequences of over 100 Mammalian species. The database is useful for phylogenetic analysis, since it allows ready retrieval of nucleotide and amino acid alignments of 13 protein coding mitochondrial genes, based on their parameters values (sequence length, p-distances, base content, transition transversion ratio, gamma).
1. Vasconcelos AT, Guimaraes AC, Castelletti CH, Caruso CS, Ribeiro C, Yokaichiya F, Armoa GR, Pereira Gda S, da Silva IT, Schrago CG, Fernandes AL, da Silveira AR, Carneiro AG, Carvalho BM, Viana CJ, Gramkow D, Lima FJ, Correa LG, Mudado Mde A, Nehab-Hess P, Souza R, Correa RL, Russo CA. (2005) MamMiBase: a mitochondrial genome database for mammalian phylogenetic studies. Bioinformatics 21: 2566-2567.
Mitochondrial genomes are frequently used in molecular evolution, including molecular systematics and phylogeny studies. In Metazoa, the mitochondrial (mt) genome (1) is of circular shape; it has a genome length ranging ~16-17 kb and a very compact gene organization, i.e., no space between genes, in some cases short overlaps of genes, presence of only one major non-coding region containing, in general, the main regulatory elements. Because of its reduced size the metazoan mt genome can be completely sequenced rather easily, thus making comparative studies possible not only at the gene but also at the genomic level. For these studies a very important prerequisite is the best alignment of the sequences under comparison. The AMmtDB database compiles the Chordata and Invertebrata multi-aligned complete mitochondrial (mt) genes coding for proteins and tRNAs available from public sequence databases (updated at August 2001). These data include genes from 113 Chordata and 47 Invertebrata complete mitochondrial genomes. The genes coding for proteins are multi-aligned based on the translated sequences and both the nucleotide and aminoacid multialignments are provided. The AMmtDB database can be retrieved through SRS and is available via the web site http://bighost.area.ba.cnr.it/mitochondriome where other mitochondrial databases developed by our group, the complete list of the sequenced mitochondrial genomes, and links to other mitochondrial sites and related information are available. Each entry in AMmtDB is related to taxonomic class specific data for the same gene. Because of the variability of the mitochondrial genomes and their usage in diversity studies, data from primary databases reporting sequences from the same species and the same genes have been analysed and grouped in gene and species specific clusters identified by a code; each cluster is stored in a multi-aligned file and the link to this file is available through the AMmtDB entries at the MV line. Further information about the variant clusters is available at the Mitochondriome Web site in the section Databases/VarMmtDB . The data selected through SRS can be viewed and managed using GeneDoc or other programs for the management of multi-aligned data depending on the user's operative system.
This work has been supported by 'Ministero Università e Ricerca Scientifica', Italy (PRIN99, Programma Biotecnologie legge 95/95-MURST 5%; Progetto MURST Cluster C03/2000, CEGBA)