An Appraisal of Human Mitochondrial DNA Instability: New Insights into the Role of Non-Canonical DNA Structures and Sequence Motifs
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{"title"=>"An Appraisal of Human Mitochondrial DNA Instability: New Insights into the Role of Non-Canonical DNA Structures and Sequence Motifs", "type"=>"journal", "authors"=>[{"first_name"=>"Pedro H.", "last_name"=>"Oliveira", "scopus_author_id"=>"55934291400"}, {"first_name"=>"Cláudia", "last_name"=>"Lobato da Silva", "scopus_author_id"=>"6506144852"}, {"first_name"=>"Joaquim M.S.", "last_name"=>"Cabral", "scopus_author_id"=>"7201350203"}], "year"=>2013, "source"=>"PLoS ONE", "identifiers"=>{"scopus"=>"2-s2.0-84875515679", "sgr"=>"84875515679", "issn"=>"19326203", "doi"=>"10.1371/journal.pone.0059907", "pmid"=>"23555828", "isbn"=>"1932-6203 (Electronic)\\r1932-6203 (Linking)", "pui"=>"368612400"}, "id"=>"77aa2e0e-fd18-3099-bc72-261f0c3fe242", "abstract"=>"Mitochondrial DNA (mtDNA) deletion mutations are frequently observed in aged postmitotic tissues and are the cause of a wide range of human disorders. Presently, the molecular bases underlying mtDNA deletion formation remain a matter of intense debate, and it is commonly accepted that several mechanisms contribute to the spectra of mutations in the mitochondrial genome. In this work we performed an extensive screening of human mtDNA deletions and evaluated the association between breakpoint density and presence of non-canonical DNA elements and over-represented sequence motifs. Our observations support the involvement of helix-distorting intrinsically curved regions and long G-tetrads in eliciting instability events. In addition, higher breakpoint densities were consistently observed within GC-skewed regions and in the close vicinity of the degenerate sequence motif YMMYMNNMMHM. A parallelism is also established with hot spot motifs previously identified in the nuclear genome, as well as with the minimal binding site for the mitochondrial transcription termination factor mTERF. This study extends the current knowledge on the mechanisms driving mitochondrial rearrangements and opens up exciting avenues for further research.", "link"=>"http://www.mendeley.com/research/appraisal-human-mitochondrial-dna-instability-new-insights-role-noncanonical-dna-structures-sequence", "reader_count"=>22, "reader_count_by_academic_status"=>{"Unspecified"=>2, "Professor > Associate Professor"=>3, "Researcher"=>6, "Student > Ph. D. Student"=>4, "Student > Master"=>3, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_user_role"=>{"Unspecified"=>2, "Professor > Associate Professor"=>3, "Researcher"=>6, "Student > Ph. D. Student"=>4, "Student > Master"=>3, "Student > Bachelor"=>3, "Professor"=>1}, "reader_count_by_subject_area"=>{"Unspecified"=>2, "Biochemistry, Genetics and Molecular Biology"=>3, "Medicine and Dentistry"=>2, "Agricultural and Biological Sciences"=>13, "Computer Science"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>13}, "Computer Science"=>{"Computer Science"=>2}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>3}, "Unspecified"=>{"Unspecified"=>2}}, "reader_count_by_country"=>{"United Kingdom"=>1, "France"=>1, "Portugal"=>1}, "group_count"=>1}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1001873"], "description"=>"<p>(A) Distribution of the 5′ and 3′ positions corresponding to 1,508 breakpoints, as well as corresponding histograms and positions along the mitochondrial genome. CR-control region; RNR-Ribosomal RNA; ND-NADH dehydrogenase; CO-cytochrome oxidase; CYTB-Cytochrome B. Black arrows correspond to the 22 tRNA genes. (B) Pie chart indicating the proportion of deletions occurring exclusively in the major arc (nucleotide positions 1–109 and 5,799–16,569), minor arc (nucleotide positions 442–5,720) or involving the origins of replication O<sub>H</sub> (nucleotide positions 110–441 bp) and O<sub>L</sub> (nucleotide positions 5,721–5,798).</p>", "links"=>[], "tags"=>["mitochondrial", "deletion"], "article_id"=>663154, "categories"=>["Biological Sciences", "Biochemistry", "Genetics", "Biophysics", "Evolutionary Biology"], "users"=>["Pedro H. Oliveira", "Cláudia Lobato da Silva", "Joaquim M. S. Cabral"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059907.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Human_mitochondrial_deletion_spectra_/663154", "title"=>"Human mitochondrial deletion spectra.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-30 05:51:43"}
  • {"files"=>["https://ndownloader.figshare.com/files/1001875"], "description"=>"<p>(A) Curvature/bendability profile of the entire mtDNA genome as computed by the bend.it algorithm (see Methods section). The exact positions corresponding to the highest curvature/bendability ratios are indicated above the corresponding peaks. (B) Density of deletion breakpoints (∑ number of breakpoints/∑ fragment sizes) computed in 0.1 kb bins flanking each curvature maximum (black bars). Also shown are the density values computed after randomization of breakpoint positions (shown in blue) or after partially randomization of breakpoint positions (shown in green) (see also Methods section). (C) Three-dimensional representations of three 0.2 kb regions harboring highly curved sequences. The exact position corresponding to each curvature maximum is highlighted in red. Additional three-dimensional representations of the remaining peaks highlighted in (A) can be found as supplementary material (<a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059907#pone.0059907.s001\" target=\"_blank\">Fig. S1</a>). Error bars represent standard deviations. * <i>p</i><0.05; *** <i>p</i><0.001.</p>", "links"=>[], "tags"=>["intrinsically", "bent", "dna", "deletion"], "article_id"=>663155, "categories"=>["Biological Sciences", "Biochemistry", "Genetics", "Biophysics", "Evolutionary Biology"], "users"=>["Pedro H. Oliveira", "Cláudia Lobato da Silva", "Joaquim M. S. Cabral"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059907.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_of_intrinsically_bent_DNA_in_the_distribution_of_deletion_breakpoints_/663155", "title"=>"Impact of intrinsically bent DNA in the distribution of deletion breakpoints.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-30 05:52:02"}
  • {"files"=>["https://ndownloader.figshare.com/files/1001878"], "description"=>"<p>(A) Sequences and locations of the DNA strings predicted to fold into G-quadruplexes, triplexes and Z-DNA. (B) Density of deletion breakpoints per 0.1 kb bins of each non-B element (black bars). Also shown are the density values computed after randomization of breakpoint positions (shown in blue) or after partially randomization of breakpoint positions (shown in green). Error bars represent standard deviations. * <i>p</i><0.05; ** <i>p</i><0.01; *** <i>p</i><0.001.</p>", "links"=>[], "tags"=>["non-canonical", "dna", "structures", "deletion"], "article_id"=>663157, "categories"=>["Biological Sciences", "Biochemistry", "Genetics", "Biophysics", "Evolutionary Biology"], "users"=>["Pedro H. Oliveira", "Cláudia Lobato da Silva", "Joaquim M. S. Cabral"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059907.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_of_the_presence_of_non_canonical_non_B_DNA_structures_on_the_distribution_of_deletion_breakpoints_/663157", "title"=>"Impact of the presence of non-canonical (non-B) DNA structures on the distribution of deletion breakpoints.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-30 05:52:15"}
  • {"files"=>["https://ndownloader.figshare.com/files/1001880"], "description"=>"<p>Variation in the density of deletion breakpoints <i>per</i> 0.1 kb with GC-skew (A) and % GC-content (B). Black bars represent the density values obtained for the human mtDNA, whereas blue and green bars respectively represent the values computed after randomization and partial randomization of breakpoint positions. Error bars represent standard deviations. * <i>p</i><0.05; ** <i>p</i><0.01; *** <i>p</i><0.001.</p>", "links"=>[], "tags"=>["gc-skew", "gc-content", "deletion"], "article_id"=>663158, "categories"=>["Biological Sciences", "Biochemistry", "Genetics", "Biophysics", "Evolutionary Biology"], "users"=>["Pedro H. Oliveira", "Cláudia Lobato da Silva", "Joaquim M. S. Cabral"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059907.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Impact_of_GC_skew_and_GC_content_in_the_distribution_of_deletion_breakpoints_/663158", "title"=>"Impact of GC-skew and % GC-content in the distribution of deletion breakpoints.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-30 05:52:32"}
  • {"files"=>["https://ndownloader.figshare.com/files/1001882"], "description"=>"<p>(A) Sequence logo of the degenerate 11-mer motif over-represented in the close vicinity (±15 bp) of the non-repeated breakpoint dataset. Representative logos were obtained from MEME and AlignACE (see <a href=\"http://www.plosone.org/article/info:doi/10.1371/journal.pone.0059907#pone.0059907.s002\" target=\"_blank\">Fig. S2</a>), and compared both manually and using the STAMP tool. Degenerate nucleotides are as follows: Y = (C or T); M = (A or C); H = (A or T or C); N = (A or T or G or C). (B) The number of occurrences of the YMMYMNNMMHM motif in the human mtDNA (black bar) is compared with those obtained from randomly shuffled genomes preserving k-tuples of 1 and 3 (respectively blue and green bars). (C) Percentage of breakpoints in terms of distance (bp) to the nearest YMMYMNNMMHM motif. Black bars represent the percentage values obtained for the human mtDNA, whereas blue and green bars respectively represent the values computed after randomization and partial randomization of deletion breakpoints. Error bars represent standard deviations. * <i>p</i><0.05; ** <i>p</i><0.01; *** <i>p</i><0.001. (D) Distribution profiles of breakpoints (red) and YMMYMNNMMHM motif (blue) along the minor arc (left) and major arc (right). Stippled lines indicate the positions of the previously identified highly bent regions as well as of the G2 and G5 motifs.</p>", "links"=>[], "tags"=>["over-represented", "motifs", "vicinity", "deletion"], "article_id"=>663160, "categories"=>["Biological Sciences", "Biochemistry", "Genetics", "Biophysics", "Evolutionary Biology"], "users"=>["Pedro H. Oliveira", "Cláudia Lobato da Silva", "Joaquim M. S. Cabral"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059907.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Search_for_over_represented_motifs_in_the_close_vicinity_of_deletion_breakpoints_/663160", "title"=>"Search for over-represented motifs in the close vicinity of deletion breakpoints.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-30 05:52:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1001883"], "description"=>"<p>The mutational events (I) may arise as a consequence of unusual DNA conformations, fragile motifs, exogenous factors, among others. These mutations will co-exist with the wild-type mtDNA in a heteroplasmic state, or eventually be selected (II) until a homoplasmic state is reached.</p>", "links"=>[], "tags"=>["illustrating", "mitochondria", "non-functional"], "article_id"=>663161, "categories"=>["Biological Sciences", "Biochemistry", "Genetics", "Biophysics", "Evolutionary Biology"], "users"=>["Pedro H. Oliveira", "Cláudia Lobato da Silva", "Joaquim M. S. Cabral"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059907.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Diagram_illustrating_the_sequence_of_events_I_II_capable_of_driving_functional_mitochondria_to_shift_to_a_partially_functional_or_non_functional_state_/663161", "title"=>"Diagram illustrating the sequence of events (I, II) capable of driving functional mitochondria to shift to a partially functional or non-functional state.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-30 05:53:12"}
  • {"files"=>["https://ndownloader.figshare.com/files/1001885", "https://ndownloader.figshare.com/files/1001886", "https://ndownloader.figshare.com/files/1001887"], "description"=>"<div><p>Mitochondrial DNA (mtDNA) deletion mutations are frequently observed in aged postmitotic tissues and are the cause of a wide range of human disorders. Presently, the molecular bases underlying mtDNA deletion formation remain a matter of intense debate, and it is commonly accepted that several mechanisms contribute to the spectra of mutations in the mitochondrial genome. In this work we performed an extensive screening of human mtDNA deletions and evaluated the association between breakpoint density and presence of non-canonical DNA elements and over-represented sequence motifs. Our observations support the involvement of helix-distorting intrinsically curved regions and long G-tetrads in eliciting instability events. In addition, higher breakpoint densities were consistently observed within GC-skewed regions and in the close vicinity of the degenerate sequence motif YMMYMNNMMHM. A parallelism is also established with hot spot motifs previously identified in the nuclear genome, as well as with the minimal binding site for the mitochondrial transcription termination factor mTERF. This study extends the current knowledge on the mechanisms driving mitochondrial rearrangements and opens up exciting avenues for further research.</p> </div>", "links"=>[], "tags"=>["appraisal", "mitochondrial", "dna", "insights", "non-canonical", "structures"], "article_id"=>663163, "categories"=>["Biological Sciences", "Biochemistry", "Genetics", "Biophysics", "Evolutionary Biology"], "users"=>["Pedro H. Oliveira", "Cláudia Lobato da Silva", "Joaquim M. S. Cabral"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0059907.s001", "https://dx.doi.org/10.1371/journal.pone.0059907.s002", "https://dx.doi.org/10.1371/journal.pone.0059907.s003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_An_Appraisal_of_Human_Mitochondrial_DNA_Instability_New_Insights_into_the_Role_of_Non_Canonical_DNA_Structures_and_Sequence_Motifs_/663163", "title"=>"An Appraisal of Human Mitochondrial DNA Instability: New Insights into the Role of Non-Canonical DNA Structures and Sequence Motifs", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-03-30 05:53:33"}

PMC Usage Stats | Further Information

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  • {"unique-ip"=>"8", "full-text"=>"9", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"8"}
  • {"unique-ip"=>"8", "full-text"=>"4", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"2", "cited-by"=>"0", "year"=>"2018", "month"=>"7"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"10"}
  • {"unique-ip"=>"7", "full-text"=>"7", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2018", "month"=>"12"}
  • {"unique-ip"=>"4", "full-text"=>"4", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"2"}
  • {"unique-ip"=>"8", "full-text"=>"11", "pdf"=>"0", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"3"}
  • {"unique-ip"=>"12", "full-text"=>"12", "pdf"=>"3", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"0", "year"=>"2019", "month"=>"4"}
  • {"unique-ip"=>"11", "full-text"=>"15", "pdf"=>"1", "scanned-summary"=>"0", "scanned-page-browse"=>"0", "figure"=>"0", "supp-data"=>"0", "cited-by"=>"1", "year"=>"2019", "month"=>"5"}

Relative Metric

{"start_date"=>"2013-01-01T00:00:00Z", "end_date"=>"2013-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Biology and life sciences", "average_usage"=>[269, 466, 588, 697, 800, 896, 988, 1076, 1165, 1254, 1340, 1417]}, {"subject_area"=>"/Biology and life sciences/Genetics", "average_usage"=>[284, 491, 620, 738, 843, 945, 1043, 1137, 1225, 1315, 1400, 1479, 1555]}, {"subject_area"=>"/Biology and life sciences/Molecular biology", "average_usage"=>[272, 466, 589, 702, 806, 903, 995, 1086, 1176, 1258, 1347, 1422, 1493]}, {"subject_area"=>"/Computer and information sciences", "average_usage"=>[297, 488, 616, 724, 828, 939, 1038, 1127, 1223, 1311, 1393, 1479, 1556]}, {"subject_area"=>"/Computer and information sciences/Network analysis", "average_usage"=>[340, 548, 701, 844, 945, 1073, 1189, 1282, 1391, 1488, 1562, 1660, 1731]}]}
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