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Sample records for ecompagt integrates mtdna

  1. eCOMPAGT – efficient Combination and Management of Phenotypes and Genotypes for Genetic Epidemiology

    PubMed Central

    Schönherr, Sebastian; Weißensteiner, Hansi; Coassin, Stefan; Specht, Günther; Kronenberg, Florian; Brandstätter, Anita

    2009-01-01

    Background High-throughput genotyping and phenotyping projects of large epidemiological study populations require sophisticated laboratory information management systems. Most epidemiological studies include subject-related personal information, which needs to be handled with care by following data privacy protection guidelines. In addition, genotyping core facilities handling cooperative projects require a straightforward solution to monitor the status and financial resources of the different projects. Description We developed a database system for an efficient combination and management of phenotypes and genotypes (eCOMPAGT) deriving from genetic epidemiological studies. eCOMPAGT securely stores and manages genotype and phenotype data and enables different user modes with different rights. Special attention was drawn on the import of data deriving from TaqMan and SNPlex genotyping assays. However, the database solution is adjustable to other genotyping systems by programming additional interfaces. Further important features are the scalability of the database and an export interface to statistical software. Conclusion eCOMPAGT can store, administer and connect phenotype data with all kinds of genotype data and is available as a downloadable version at . PMID:19432954

  2. Therapeutic Targeting of the Mitochondria Initiates Excessive Superoxide Production and Mitochondrial Depolarization Causing Decreased mtDNA Integrity

    PubMed Central

    Pokrzywinski, Kaytee L.; Biel, Thomas G.; Kryndushkin, Dmitry; Rao, V. Ashutosh

    2016-01-01

    Mitochondrial dysregulation is closely associated with excessive reactive oxygen species (ROS) production. Altered redox homeostasis has been implicated in the onset of several diseases including cancer. Mitochondrial DNA (mtDNA) and proteins are particularly sensitive to ROS as they are in close proximity to the respiratory chain (RC). Mitoquinone (MitoQ), a mitochondria-targeted redox agent, selectively damages breast cancer cells possibly through damage induced via enhanced ROS production. However, the effects of MitoQ and other triphenylphosphonium (TPP+) conjugated agents on cancer mitochondrial homeostasis remain unknown. The primary objective of this study was to determine the impact of mitochondria-targeted agent [(MTAs) conjugated to TPP+: mitoTEMPOL, mitoquinone and mitochromanol-acetate] on mitochondrial physiology and mtDNA integrity in breast (MDA-MB-231) and lung (H23) cancer cells. The integrity of the mtDNA was assessed by quantifying the degree of mtDNA fragmentation and copy number, as well as by measuring mitochondrial proteins essential to mtDNA stability and maintenance (TFAM, SSBP1, TWINKLE, POLG and POLRMT). Mitochondrial status was evaluated by measuring superoxide production, mitochondrial membrane depolarization, oxygen consumption, extracellular acidification and mRNA or protein levels of the RC complexes along with TCA cycle activity. In this study, we demonstrated that all investigated MTAs impair mitochondrial health and decrease mtDNA integrity in MDA-MB-231 and H23 cells. However, differences in the degree of mitochondrial damage and mtDNA degradation suggest unique properties among each MTA that may be cell line, dose and time dependent. Collectively, our study indicates the potential for TPP+ conjugated molecules to impair breast and lung cancer cells by targeting mitochondrial homeostasis. PMID:28030582

  3. DNA Ligase III is critical for mtDNA integrity but not Xrcc1-mediated nuclear DNA repair

    PubMed Central

    Gao, Yankun; Katyal, Sachin; Lee, Youngsoo; Zhao, Jingfeng; Rehg, Jerold E.; Russell, Helen R.; McKinnon, Peter J.

    2011-01-01

    DNA replication and repair in mammalian cells involves three distinct DNA ligases; ligase I (Lig1), ligase III (Lig3) and ligase IV (Lig4)1. Lig3 is considered a key ligase during base excision repair because its stability depends upon its nuclear binding partner Xrcc1, a critical factor for this DNA repair pathway2,3. Lig3 is also present in the mitochondria where its role in mitochondrial DNA (mtDNA) maintenance is independent of Xrcc14. However, the biological role of Lig3 is unclear as inactivation of murine Lig3 results in early embryonic lethality5. Here we report that Lig3 is essential for mtDNA integrity but dispensable for nuclear DNA repair. Inactivation of Lig3 in the mouse nervous system resulted in mtDNA loss leading to profound mitochondrial dysfunction, disruption of cellular homeostasis and incapacitating ataxia. Similarly, inactivation of Lig3 in cardiac muscle resulted in mitochondrial dysfunction and defective heart pump function leading to heart failure. However, Lig3 inactivation did not result in nuclear DNA repair deficiency, indicating essential DNA repair functions of Xrcc1 can occur in the absence of Lig3. Instead, we found that Lig1 was critical for DNA repair, but in a cooperative manner with Lig3. Additionally, Lig3 deficiency did not recapitulate the hallmark features of neural Xrcc1 inactivation such as DNA damage-induced cerebellar interneuron loss6, further underscoring functional separation of these DNA repair factors. Therefore, our data reveal that the critical biological role of Lig3 is to maintain mtDNA integrity and not Xrcc1-dependent DNA repair. PMID:21390131

  4. Integrated Analyses of Cuticular Hydrocarbons, Chromosome and mtDNA in the Neotropical Social Wasp Mischocyttarus consimilis Zikán (Hymenoptera, Vespidae).

    PubMed

    Cunha, D A S; Menezes, R S T; Costa, M A; Lima, S M; Andrade, L H C; Antonialli, W F

    2017-03-02

    In the present work, we explored multiple data from different biological levels such as cuticular hydrocarbons, chromosomal features, and mtDNA sequences in the Neotropical social wasp Mischocyttarus consimilis (J.F. Zikán). Particularly, we explored the genetic and chemical differentiation level within and between populations of this insect. Our dataset revealed shallow intraspecific differentiation in M. consimilis. The similarity among the analyzed samples can probably be due to the geographical proximity where the colonies were sampled, and we argue that Paraná River did not contribute effectively as a historical barrier to this wasp.

  5. Linear mtDNA fragments and unusual mtDNA rearrangements associated with pathological deficiency of MGME1 exonuclease

    PubMed Central

    Nicholls, Thomas J.; Zsurka, Gábor; Peeva, Viktoriya; Schöler, Susanne; Szczesny, Roman J.; Cysewski, Dominik; Reyes, Aurelio; Kornblum, Cornelia; Sciacco, Monica; Moggio, Maurizio; Dziembowski, Andrzej; Kunz, Wolfram S.; Minczuk, Michal

    2014-01-01

    MGME1, also known as Ddk1 or C20orf72, is a mitochondrial exonuclease found to be involved in the processing of mitochondrial DNA (mtDNA) during replication. Here, we present detailed insights on the role of MGME1 in mtDNA maintenance. Upon loss of MGME1, elongated 7S DNA species accumulate owing to incomplete processing of 5′ ends. Moreover, an 11-kb linear mtDNA fragment spanning the entire major arc of the mitochondrial genome is generated. In contrast to control cells, where linear mtDNA molecules are detectable only after nuclease S1 treatment, the 11-kb fragment persists in MGME1-deficient cells. In parallel, we observed characteristic mtDNA duplications in the absence of MGME1. The fact that the breakpoints of these mtDNA rearrangements do not correspond to either classical deletions or the ends of the linear 11-kb fragment points to a role of MGME1 in processing mtDNA ends, possibly enabling their repair by homologous recombination. In agreement with its functional involvement in mtDNA maintenance, we show that MGME1 interacts with the mitochondrial replicase PolgA, suggesting that it is a constituent of the mitochondrial replisome, to which it provides an additional exonuclease activity. Thus, our results support the viewpoint that MGME1-mediated mtDNA processing is essential for faithful mitochondrial genome replication and might be required for intramolecular recombination of mtDNA. PMID:24986917

  6. Keeping mtDNA in Shape between Generations

    PubMed Central

    Stewart, James B.; Larsson, Nils-Göran

    2014-01-01

    Since the unexpected discovery that mitochondria contain their own distinct DNA molecules, studies of the mitochondrial DNA (mtDNA) have yielded many surprises. In animals, transmission of the mtDNA genome is explicitly non-Mendelian, with a very high number of genome copies being inherited from the mother after a drastic bottleneck. Recent work has begun to uncover the molecular details of this unusual mode of transmission. Many surprising variations in animal mitochondrial biology are known; however, a series of recent studies have identified a core of evolutionarily conserved mechanisms relating to mtDNA inheritance, e.g., mtDNA bottlenecks during germ cell development, selection against specific mtDNA mutation types during maternal transmission, and targeted destruction of sperm mitochondria. In this review, we outline recent literature on the transmission of mtDNA in animals and highlight the implications for human health and ageing. PMID:25299061

  7. Spotlight on the relevance of mtDNA in cancer.

    PubMed

    Cruz-Bermúdez, A; Vicente-Blanco, R J; Gonzalez-Vioque, E; Provencio, M; Fernández-Moreno, M Á; Garesse, R

    2017-04-01

    The potential role of the mitochondrial genome has recently attracted interest because of its high mutation frequency in tumors. Different aspects of mtDNA make it relevant for cancer's biology, such as it encodes a limited but essential number of genes for OXPHOS biogenesis, it is particularly susceptible to mutations, and its copy number can vary. Moreover, most ROS in mitochondria are produced by the electron transport chain. These characteristics place the mtDNA in the center of multiple signaling pathways, known as mitochondrial retrograde signaling, which modifies numerous key processes in cancer. Cybrid studies support that mtDNA mutations are relevant and exert their effect through a modification of OXPHOS function and ROS production. However, there is still much controversy regarding the clinical relevance of mtDNA mutations. New studies should focus more on OXPHOS dysfunction associated with a specific mutational signature rather than the presence of mutations in the mtDNA.

  8. Developing equine mtDNA profiling for forensic application.

    PubMed

    Gurney, Susan M R; Schneider, Sandra; Pflugradt, René; Barrett, Elizabeth; Forster, Anna Catharina; Brinkmann, Bernd; Jansen, Thomas; Forster, Peter

    2010-11-01

    Horse mtDNA profiling can be useful in forensic work investigating degraded samples, hair shafts or highly dilute samples. Degraded DNA often does not allow sequencing of fragments longer than 200 nucleotides. In this study we therefore search for the most discriminatory sections within the hypervariable horse mtDNA control region. Among a random sample of 39 horses, 32 different sequences were identified in a stretch of 921 nucleotides. The sequences were assigned to the published mtDNA types A-G, and to a newly labelled minor type H. The random match probability within the analysed samples is 3.61%, and the average pairwise sequence difference is 15 nucleotides. In a "sliding window" analysis of 200-nucleotide sections of the mtDNA control region, we find that the known repetitive central motif divides the mtDNA control region into a highly diverse segment and a markedly less discriminatory segment.

  9. The mutation rate of the human mtDNA deletion mtDNA4977.

    PubMed

    Shenkar, R; Navidi, W; Tavaré, S; Dang, M H; Chomyn, A; Attardi, G; Cortopassi, G; Arnheim, N

    1996-10-01

    The human mitochondrial mutation mtDNA4977 is a 4,977-bp deletion that originates between two 13-bp direct repeats. We grew 220 colonies of cells, each from a single human cell. For each colony, we counted the number of cells and amplified the DNA by PCR to test for the presence of a deletion. To estimate the mutation fate, we used a model that describes the relationship between the mutation rate and the probability that a colony of a given size will contain no mutants, taking into account such factors as possible mitochondrial turnover and mistyping due to PCR error. We estimate that the mutation rate for mtDNA4977 in cultured human cells is 5.95 x 10(-8) per mitochondrial genome replication. This method can be applied to specific chromosomal, as well as mitochondrial, mutations.

  10. Transcriptional quiescence of paternal mtDNA in cyprinid fish embryos

    PubMed Central

    Wen, Ming; Peng, Liangyue; Hu, Xinjiang; Zhao, Yuling; Liu, Shaojun; Hong, Yunhan

    2016-01-01

    Mitochondrial homoplasmy signifies the existence of identical copies of mitochondrial DNA (mtDNA) and is essential for normal development, as heteroplasmy causes abnormal development and diseases in human. Homoplasmy in many organisms is ensured by maternal mtDNA inheritance through either absence of paternal mtDNA delivery or early elimination of paternal mtDNA. However, whether paternal mtDNA is transcribed has remained unknown. Here we report that paternal mtDNA shows late elimination and transcriptional quiescence in cyprinid fishes. Paternal mtDNA was present in zygotes but absent in larvae and adult organs of goldfish and blunt-snout bream, demonstrating paternal mtDNA delivery and elimination for maternal mtDNA inheritance. Surprisingly, paternal mtDNA remained detectable up to the heartbeat stage, suggesting its late elimination leading to embryonic heteroplasmy up to advanced embryogenesis. Most importantly, we never detected the cytb RNA of paternal mtDNA at all stages when paternal mtDNA was easily detectable, which reveals that paternal mtDNA is transcriptionally quiescent and thus excludes its effect on the development of heteroplasmic embryos. Therefore, paternal mtDNA in cyprinids shows late elimination and transcriptional quiescence. Clearly, transcriptional quiescence of paternal mtDNA represents a new mechanism for maternal mtDNA inheritance and provides implications for treating mitochondrion-associated diseases by mitochondrial transfer or replacement. PMID:27334806

  11. Revealing the hidden complexities of mtDNA inheritance.

    PubMed

    White, Daniel James; Wolff, Jonci Nikolai; Pierson, Melanie; Gemmell, Neil John

    2008-12-01

    Mitochondrial DNA (mtDNA) is a pivotal tool in molecular ecology, evolutionary and population genetics. The power of mtDNA analyses derives from a relatively high mutation rate and the apparent simplicity of mitochondrial inheritance (maternal, without recombination), which has simplified modelling population history compared to the analysis of nuclear DNA. However, in biology things are seldom simple, and advances in DNA sequencing and polymorphism detection technology have documented a growing list of exceptions to the central tenets of mitochondrial inheritance, with paternal leakage, heteroplasmy and recombination now all documented in multiple systems. The presence of paternal leakage, recombination and heteroplasmy can have substantial impact on analyses based on mtDNA, affecting phylogenetic and population genetic analyses, estimates of the coalescent and the myriad of other parameters that are dependent on such estimates. Here, we review our understanding of mtDNA inheritance, discuss how recent findings mean that established ideas may need to be re-evaluated, and we assess the implications of these new-found complications for molecular ecologists who have relied for decades on the assumption of a simpler mode of inheritance. We show how it is possible to account for recombination and heteroplasmy in evolutionary and population analyses, but that accurate estimates of the frequencies of biparental inheritance and recombination are needed. We also suggest how nonclonal inheritance of mtDNA could be exploited, to increase the ways in which mtDNA can be used in analyses.

  12. MtDNA haplogroups and elite Korean athlete status.

    PubMed

    Kim, K C; Cho, H I; Kim, W

    2012-01-01

    Mitochondrial DNA (mtDNA) variation has recently been suggested to have an association with athletic performance or physical endurance. Since mtDNA is haploid and lacks recombination, specific mutations in the mtDNA genome associated with human exercise tolerance or intolerance arise and remain in particular genetic backgrounds referred to as haplogroups. To assess the possible contribution of mtDNA haplogroup-specific variants to differences in elite athletic performance, we performed a population-based study of 152 Korean elite athletes [77 sprint/power athletes (SPA) and 75 endurance/middle-power athletes (EMA)] and 265 non-athletic controls (CON). The overall haplogroup distribution of EMA differed significantly from CON (p<0.01), but that of SPA did not. The EMA have an excess of haplogroups M* (OR 4.38, 95% CI 1.63-11.79, p=0.003) and N9 (OR 2.32, 95% CI 0.92-5.81, p=0.042), but a dearth of haplogroup B (OR 0.26, 95% CI 0.09-0.75, p=0.003) compared with the CON. Thus, our data imply that specific mtDNA lineages may provide a significant effect on elite Korean endurance status, although functional studies with larger sample sizes are necessary to further substantiate these findings.

  13. Random Genetic Drift Determines the Level of Mutant mtDNA in Human Primary Oocytes

    PubMed Central

    Brown, D. T.; Samuels, D. C.; Michael, E. M.; Turnbull, D. M.; Chinnery, P. F.

    2001-01-01

    We measured the proportion of mutant mtDNA (mutation load) in 82 primary oocytes from a woman who harbored the A3243G mtDNA mutation. The frequency distribution of mutation load indicates that random drift is the principal mechanism that determines the level of mutant mtDNA within individual oocytes. PMID:11133360

  14. Analysis of BRCA1 and mtDNA haplotypes and mtDNA polymorphism in familial breast cancer.

    PubMed

    Gutiérrez Povedano, Cristina; Salgado, Josefa; Gil, Carmen; Robles, Maitane; Patiño-García, Ana; García-Foncillas, Jesús

    2015-04-01

    Mitochondrial DNA (mtDNA) defects have been postulated to play an important role in the modulation and/or progression of cancer. In the past decade, a wide spectrum of mtDNA variations have been suggested as potentially sensitive and specific biomarkers for several human cancer types. In this context, single nucleotide polymorphisms (SNPs) described as protective or risk variants have been published, in particular in breast cancer, though not without controversy. Moreover, many mtDNA haplogroups have been associated with different phenotypes and diseases. We genotyped 18 SNPs, 15 of them defining European mtDNA haplogroups, including SNPs described as protective or risk variants, 7 SNPs that determine BRCA1 haplotypes and a BRCA1 intron 7 polymorphism. We included in this study 90 Caucasian unrelated women with breast cancer with familial criteria and 96 controls. Our aim was to clarify the importance of any of these SNPs, mitochondrial haplogroups and BRCA1 haplotypes in the modulation of breast cancer. We detected no significant differences in the distribution of BRCA1 haplotypes between patients and controls. Haplogroup U and the 12308G variant of mtDNA were overrepresented within the control group (p = 0.005 and p = 0.036, respectively) compared to breast cancer. Finally, we identified a significant association between the BRCA1 intron 7 polymorphism and BRCA1 haplotypes. Specifically, (TTC)6/6 and (TTC)6/7 genotypes with the seven polymorphic site cassette of "H2-like" haplotypes, and the (TTC)7/7 genotype associated with the "H1-like" haplotypes (p < 0.001).

  15. Mitochondrial disease in childhood: mtDNA encoded.

    PubMed

    Saneto, Russell P; Sedensky, Margret M

    2013-04-01

    Since the first description of a mitochondrial DNA (mtDNA)-associated disease in the late 1980s, there have been more than 275 mutations within the mtDNA genome described causing human disease. The phenotypic expression of these disorders is vast, as disturbances of the unique physiology of mitochondria can create a wide range of clinical heterogeneity. Features of heteroplasmy, threshold effect, genetic bottleneck, mtDNA depletion, mitotic segregation, and maternal inheritance have been identified and described as a result of novel biochemical and genetic controls of mitochondrial function. We hope that as we unfold this fascinating part of clinical medicine, the reader will see how alterations in the tapestry of mitochondrial biochemistry and genetics can give rise to human illness.

  16. Reduced Mtdna Diversity in the Ngobe Amerinds of Panama

    PubMed Central

    Kolman, C. J.; Bermingham, E.; Cooke, R.; Ward, R. H.; Arias, T. D.; Guionneau-Sinclair, F.

    1995-01-01

    Mitochondrial DNA (mtDNA) haplotype diversity was determined for 46 Ngobe Amerinds sampled widely across their geographic range in western Panama. The Ngobe data were compared with mtDNA control region I sequences from two additional Amerind groups located at the northern and southern extremes of Amerind distribution, the Nuu-Chah-Nulth of the Pacific Northwest and the Chilean Mapuche and from one Na-Dene group, the Haida of the Pacific Northwest. The Ngobe exhibit the lowest mtDNA control region sequence diversity yet reported for an Amerind group. Moreover, they carry only two of the four Amerind founding lineages first described by Wallace and coworkers. We posit that the Ngobe passed through a population bottleneck caused by ethnogenesis from a small founding population and/or European conquest and colonization. Dating of the Ngobe population expansion using the HARPENDING et al. approach to the analysis of pairwise genetic differences indicates a Ngobe expansion at roughly 6800 years before present (range: 1850-14,000 years before present), a date more consistent with a bottleneck at Chibcha ethnogenesis than a conquest-based event. PMID:7635293

  17. Similar patterns of clonally expanded somatic mtDNA mutations in the colon of heterozygous mtDNA mutator mice and ageing humans

    PubMed Central

    Baines, Holly L.; Stewart, James B.; Stamp, Craig; Zupanic, Anze; Kirkwood, Thomas B.L.; Larsson, Nils-Göran; Turnbull, Douglass M.; Greaves, Laura C.

    2014-01-01

    Clonally expanded mitochondrial DNA (mtDNA) mutations resulting in focal respiratory chain deficiency in individual cells are proposed to contribute to the ageing of human tissues that depend on adult stem cells for self-renewal; however, the consequences of these mutations remain unclear. A good animal model is required to investigate this further; but it is unknown whether mechanisms for clonal expansion of mtDNA mutations, and the mutational spectra, are similar between species. Here we show that mice, heterozygous for a mutation disrupting the proof-reading activity of mtDNA polymerase (PolgA+/mut) resulting in an increased mtDNA mutation rate, accumulate clonally expanded mtDNA point mutations in their colonic crypts with age. This results in focal respiratory chain deficiency, and by 81 weeks of age these animals exhibit a similar level and pattern of respiratory chain deficiency to 70-year-old human subjects. Furthermore, like in humans, the mtDNA mutation spectrum appears random and there is an absence of selective constraints. Computer simulations show that a random genetic drift model of mtDNA clonal expansion can accurately model the data from the colonic crypts of wild-type, PolgA+/mut animals, and humans, providing evidence for a similar mechanism for clonal expansion of mtDNA point mutations between these mice and humans. PMID:24915468

  18. The effects of a wheat germ rich diet on oxidative mtDNA damage, mtDNA copy number and antioxidant enzyme activities in aging Drosophila.

    PubMed

    Mutlu, Ayse Gul

    2013-03-01

    The free radical theory of aging posits that the accumulation of macromolecular damage induced by toxic reactive oxygen species plays a central role in the aging process. Therefore consumption of dietary antioxidants appears to be of great importance. Wheat germ have strong antioxidant properties. Aim of this study is investigate the effects of a wheat germ rich diet on oxidative mtDNA damage, mtDNA copy number and antioxidant enzyme activities in Drosophila. Current results suggested that dietary wheat germ enhances the activities of antioxidant enzymes in Drosophila. There was no statistically difference in mtDNA damage and mtDNA copy number results of "Wheat Germ" and "Refined White Flour" feed groups. mtDNA damage slightly increased with aging in both groups but these changes were no statistically different.

  19. Single-cell analysis of intercellular heteroplasmy of mtDNA in Leber hereditary optic neuropathy

    SciTech Connect

    Kobayashi, Y.; Sharpe, H.; Brown, N.

    1994-07-01

    The authors have investigated the distribution of mutant mtDNA molecules in single cells from a patient with Leber hereditary optic neuropathy (LHON). LHON is a maternally inherited disease that is characterized by a sudden-onset bilateral loss of central vision, which typically occurs in early adulthood. More than 50% of all LHON patients carry an mtDNA mutation at nucleotide position 11778. This nucleotide change converts a highly conserved arginine residue to histidine at codon 340 in the NADH-ubiquinone oxidoreductase subunit 4 (ND4) gene of mtDNA. In the present study, the authors used PCR amplification of mtDNA from lymphocytes to investigate mtDNA heteroplasmy at the single-cell level in a LHON patient. They found that most cells were either homoplasmic normal or homoplasmic mutant at nucleotide position 11778. Some (16%) cells contained both mutant and normal mtDNA.

  20. ER-mitochondria contacts couple mtDNA synthesis with mitochondrial division in human cells.

    PubMed

    Lewis, Samantha C; Uchiyama, Lauren F; Nunnari, Jodi

    2016-07-15

    Mitochondrial DNA (mtDNA) encodes RNAs and proteins critical for cell function. In human cells, hundreds to thousands of mtDNA copies are replicated asynchronously, packaged into protein-DNA nucleoids, and distributed within a dynamic mitochondrial network. The mechanisms that govern how nucleoids are chosen for replication and distribution are not understood. Mitochondrial distribution depends on division, which occurs at endoplasmic reticulum (ER)-mitochondria contact sites. These sites were spatially linked to a subset of nucleoids selectively marked by mtDNA polymerase and engaged in mtDNA synthesis--events that occurred upstream of mitochondrial constriction and division machine assembly. Our data suggest that ER tubules proximal to nucleoids are necessary but not sufficient for mtDNA synthesis. Thus, ER-mitochondria contacts coordinate licensing of mtDNA synthesis with division to distribute newly replicated nucleoids to daughter mitochondria.

  1. An enhanced MITOMAP with a global mtDNA mutational phylogeny

    PubMed Central

    Ruiz-Pesini, Eduardo; Lott, Marie T.; Procaccio, Vincent; Poole, Jason C.; Brandon, Marty C.; Mishmar, Dan; Yi, Christina; Kreuziger, James; Baldi, Pierre; Wallace, Douglas C.

    2007-01-01

    The MITOMAP () data system for the human mitochondrial genome has been greatly enhanced by the addition of a navigable mutational mitochondrial DNA (mtDNA) phylogenetic tree of ∼3000 mtDNA coding region sequences plus expanded pathogenic mutation tables and a nuclear-mtDNA pseudogene (NUMT) data base. The phylogeny reconstructs the entire mutational history of the human mtDNA, thus defining the mtDNA haplogroups and differentiating ancient from recent mtDNA mutations. Pathogenic mutations are classified by both genotype and phenotype, and the NUMT sequences permits detection of spurious inclusion of pseudogene variants during mutation analysis. These additions position MITOMAP for the implementation of our automated mtDNA sequence analysis system, Mitomaster. PMID:17178747

  2. [Studies on mtDNA of Ustilago maydis. II. Restriction mapping].

    PubMed

    Feng, G H; Cheng, W; Lu, S Y

    1991-01-01

    A restriction map was constructed for mtDNA of Ustilago maydis. The fragment order for each restriction enzyme was determined by DNA hybridization and fragment overlapping. The restriction sites were located by analysing the secondary digestions of the cloned mtDNA fragments. It was also found that the mtDNA of U. maydis was a circle molecule (60.7 kb), without recognizable repeat sequence.

  3. No recombination of mtDNA after heteroplasmy for 50 generations in the mouse maternal germline

    PubMed Central

    Hagström, Erik; Freyer, Christoph; Battersby, Brendan J.; Stewart, James B.; Larsson, Nils-Göran

    2014-01-01

    Variants of mitochondrial DNA (mtDNA) are commonly used as markers to track human evolution because of the high sequence divergence and exclusive maternal inheritance. It is assumed that the inheritance is clonal, i.e. that mtDNA is transmitted between generations without germline recombination. In contrast to this assumption, a number of studies have reported the presence of recombinant mtDNA molecules in cell lines and animal tissues, including humans. If germline recombination of mtDNA is frequent, it would strongly impact phylogenetic and population studies by altering estimates of coalescent time and branch lengths in phylogenetic trees. Unfortunately, this whole area is controversial and the experimental approaches have been widely criticized as they often depend on polymerase chain reaction (PCR) amplification of mtDNA and/or involve studies of transformed cell lines. In this study, we used an in vivo mouse model that has had germline heteroplasmy for a defined set of mtDNA mutations for more than 50 generations. To assess recombination, we adapted and validated a method based on cloning of single mtDNA molecules in the λ phage, without prior PCR amplification, followed by subsequent mutation analysis. We screened 2922 mtDNA molecules and found no germline recombination after transmission of mtDNA under genetically and evolutionary relevant conditions in mammals. PMID:24163253

  4. How few whales were there after whaling? Inference from contemporary mtDNA diversity.

    PubMed

    Jackson, J A; Patenaude, N J; Carroll, E L; Baker, C Scott

    2008-01-01

    Reconstructing the history of exploited populations of whales requires fitting a trajectory through at least three points in time: (i) prior to exploitation, when abundance is assumed to be at the maximum allowed by environmental carrying capacity; (ii) the point of minimum abundance or 'bottleneck', usually near the time of protection or the abandonment of the hunt; and (iii) near the present, when protected populations are assumed to have undergone some recovery. As historical abundance is usually unknown, this trajectory must be extrapolated according to a population dynamic model using catch records, an assumed rate of increase and an estimate of current abundance, all of which have received considerable attention by the International Whaling Commission (IWC). Relatively little attention has been given to estimating minimum abundance (N(min)), although it is clear that genetic and demographic forces at this point are critical to the potential for recovery or extinction of a local population. We present a general analytical framework to improve estimates of N(min) using the number of mtDNA haplotypes (maternal lineages) surviving in a contemporary population of whales or other exploited species. We demonstrate the informative potential of this parameter as an a posteriori constraint on Bayesian logistic population dynamic models based on the IWC Comprehensive Assessment of the intensively exploited southern right whales (Eubalaena australis) and published surveys of mtDNA diversity for this species. Estimated historical trajectories from all demographic scenarios suggested a substantial loss of mtDNA haplotype richness as a result of 19th century commercial whaling and 20th century illegal whaling by the Soviet Union. However, the relatively high rates of population increase used by the IWC assessment predicted a bottleneck that was implausibly narrow (median, 67 mature females), given our corrected estimates of N(min). Further, high levels of remnant sequence

  5. Din7 and Mhr1 expression levels regulate double-strand-break-induced replication and recombination of mtDNA at ori5 in yeast.

    PubMed

    Ling, Feng; Hori, Akiko; Yoshitani, Ayako; Niu, Rong; Yoshida, Minoru; Shibata, Takehiko

    2013-06-01

    The Ntg1 and Mhr1 proteins initiate rolling-circle mitochondrial (mt) DNA replication to achieve homoplasmy, and they also induce homologous recombination to maintain mitochondrial genome integrity. Although replication and recombination profoundly influence mitochondrial inheritance, the regulatory mechanisms that determine the choice between these pathways remain unknown. In Saccharomyces cerevisiae, double-strand breaks (DSBs) introduced by Ntg1 at the mitochondrial replication origin ori5 induce homologous DNA pairing by Mhr1, and reactive oxygen species (ROS) enhance production of DSBs. Here, we show that a mitochondrial nuclease encoded by the nuclear gene DIN7 (DNA damage inducible gene) has 5'-exodeoxyribonuclease activity. Using a small ρ(-) mtDNA bearing ori5 (hypersuppressive; HS) as a model mtDNA, we revealed that DIN7 is required for ROS-enhanced mtDNA replication and recombination that are both induced at ori5. Din7 overproduction enhanced Mhr1-dependent mtDNA replication and increased the number of residual DSBs at ori5 in HS-ρ(-) cells and increased deletion mutagenesis at the ori5 region in ρ(+) cells. However, simultaneous overproduction of Mhr1 suppressed all of these phenotypes and enhanced homologous recombination. Our results suggest that after homologous pairing, the relative activity levels of Din7 and Mhr1 modulate the preference for replication versus homologous recombination to repair DSBs at ori5.

  6. Metabolic rescue in pluripotent cells from patients with mtDNA disease.

    PubMed

    Ma, Hong; Folmes, Clifford D L; Wu, Jun; Morey, Robert; Mora-Castilla, Sergio; Ocampo, Alejandro; Ma, Li; Poulton, Joanna; Wang, Xinjian; Ahmed, Riffat; Kang, Eunju; Lee, Yeonmi; Hayama, Tomonari; Li, Ying; Van Dyken, Crystal; Gutierrez, Nuria Marti; Tippner-Hedges, Rebecca; Koski, Amy; Mitalipov, Nargiz; Amato, Paula; Wolf, Don P; Huang, Taosheng; Terzic, Andre; Laurent, Louise C; Izpisua Belmonte, Juan Carlos; Mitalipov, Shoukhrat

    2015-08-13

    Mitochondria have a major role in energy production via oxidative phosphorylation, which is dependent on the expression of critical genes encoded by mitochondrial (mt)DNA. Mutations in mtDNA can cause fatal or severely debilitating disorders with limited treatment options. Clinical manifestations vary based on mutation type and heteroplasmy (that is, the relative levels of mutant and wild-type mtDNA within each cell). Here we generated genetically corrected pluripotent stem cells (PSCs) from patients with mtDNA disease. Multiple induced pluripotent stem (iPS) cell lines were derived from patients with common heteroplasmic mutations including 3243A>G, causing mitochondrial encephalomyopathy and stroke-like episodes (MELAS), and 8993T>G and 13513G>A, implicated in Leigh syndrome. Isogenic MELAS and Leigh syndrome iPS cell lines were generated containing exclusively wild-type or mutant mtDNA through spontaneous segregation of heteroplasmic mtDNA in proliferating fibroblasts. Furthermore, somatic cell nuclear transfer (SCNT) enabled replacement of mutant mtDNA from homoplasmic 8993T>G fibroblasts to generate corrected Leigh-NT1 PSCs. Although Leigh-NT1 PSCs contained donor oocyte wild-type mtDNA (human haplotype D4a) that differed from Leigh syndrome patient haplotype (F1a) at a total of 47 nucleotide sites, Leigh-NT1 cells displayed transcriptomic profiles similar to those in embryo-derived PSCs carrying wild-type mtDNA, indicative of normal nuclear-to-mitochondrial interactions. Moreover, genetically rescued patient PSCs displayed normal metabolic function compared to impaired oxygen consumption and ATP production observed in mutant cells. We conclude that both reprogramming approaches offer complementary strategies for derivation of PSCs containing exclusively wild-type mtDNA, through spontaneous segregation of heteroplasmic mtDNA in individual iPS cell lines or mitochondrial replacement by SCNT in homoplasmic mtDNA-based disease.

  7. Within-population genetic effects of mtDNA on metabolic rate in Drosophila subobscura.

    PubMed

    Kurbalija Novičić, Z; Immonen, E; Jelić, M; AnÐelković, M; Stamenković-Radak, M; Arnqvist, G

    2015-02-01

    A growing body of research supports the view that within-species sequence variation in the mitochondrial genome (mtDNA) is functional, in the sense that it has important phenotypic effects. However, most of this empirical foundation is based on comparisons across populations, and few studies have addressed the functional significance of mtDNA polymorphism within populations. Here, using mitonuclear introgression lines, we assess differences in whole-organism metabolic rate of adult Drosophila subobscura fruit flies carrying either of three different sympatric mtDNA haplotypes. We document sizeable, up to 20%, differences in metabolic rate across these mtDNA haplotypes. Further, these mtDNA effects are to some extent sex specific. We found no significant nuclear or mitonuclear genetic effects on metabolic rate, consistent with a low degree of linkage disequilibrium between mitochondrial and nuclear genes within populations. The fact that mtDNA haplotype variation within a natural population affects metabolic rate, which is a key physiological trait with important effects on life-history traits, adds weight to the emergent view that mtDNA haplotype variation is under natural selection and it revitalizes the question as to what processes act to maintain functional mtDNA polymorphism within populations.

  8. Ethidium bromide as a marker of mtDNA replication in living cells

    NASA Astrophysics Data System (ADS)

    Villa, Anna Maria; Fusi, Paola; Pastori, Valentina; Amicarelli, Giulia; Pozzi, Chiara; Adlerstein, Daniel; Doglia, Silvia Maria

    2012-04-01

    Mitochondrial DNA (mtDNA) in tumor cells was found to play an important role in maintaining the malignant phenotype. Using laser scanning confocal fluorescence microscopy (LSCFM) in a recent work, we reported a variable fluorescence intensity of ethidium bromide (EB) in mitochondria nucleoids of living carcinoma cells. Since when EB is bound to nucleic acids its fluorescence is intensified; a higher EB fluorescence intensity could reflect a higher DNA accessibility to EB, suggesting a higher mtDNA replication activity. To prove this hypothesis, in the present work we studied, by LSCFM, the EB fluorescence in mitochondria nucleoids of living neuroblastoma cells, a model system in which differentiation affects the level of mtDNA replication. A drastic decrease of fluorescence was observed after differentiation. To correlate EB fluorescence intensity to the mtDNA replication state, we evaluated the mtDNA nascent strands content by ligation-mediated real-time PCR, and we found a halved amount of replicating mtDNA molecules in differentiating cells. A similar result was obtained by BrdU incorporation. These results indicate that the low EB fluorescence of nucleoids in differentiated cells is correlated to a low content of replicating mtDNA, suggesting that EB may be used as a marker of mtDNA replication in living cells.

  9. Oxidants and not alkylating agents induce rapid mtDNA loss and mitochondrial dysfunction

    PubMed Central

    Furda, Amy M.; Marrangoni, Adele M.; Lokshin, Anna; Van Houten, Bennett

    2013-01-01

    Mitochondrial DNA (mtDNA) is essential for proper mitochondrial function and encodes 22 tRNAs, 2 rRNAs and 13 polypeptides that make up subunits of complex I, III, IV, in the electron transport chain and complex V, the ATP synthase. Although mitochondrial dysfunction has been implicated in processes such as premature aging, neurodegeneration, and cancer, it has not been shown whether persistent mtDNA damage causes a loss of oxidative phosphorylation. We addressed this question by treating mouse embryonic fibroblasts with either hydrogen peroxide (H2O2) or the alkylating agent methyl methanesulfonate (MMS) and measuring several endpoints, including mtDNA damage and repair rates using QPCR, levels of mitochondrial- and nuclear-encoded proteins using antibody analysis, and a pharmacologic profile of mitochondria using the Seahorse Extracellular Flux Analyzer. We show that a 60 min treatment with H2O2 causes persistent mtDNA lesions, mtDNA loss, decreased levels of a nuclear-encoded mitochondrial subunit, a loss of ATP-linked oxidative phosphorylation and a loss of total reserve capacity. Conversely, a 60 min treatment with 2 mM MMS causes persistent mtDNA lesions but no mtDNA loss, no decrease in levels of a nuclear-encoded mitochondrial subunit, and no mitochondrial dysfunction. These results suggest that persistent mtDNA damage is not sufficient to cause mitochondrial dysfunction. PMID:22766155

  10. Mitochondrial DNA (mtDNA) biogenesis: visualization and duel incorporation of BrdU and EdU into newly synthesized mtDNA in vitro.

    PubMed

    Lentz, Stephen I; Edwards, James L; Backus, Carey; McLean, Lisa L; Haines, Kristine M; Feldman, Eva L

    2010-02-01

    Mitochondria are key regulators of cellular energy and are the focus of a large number of studies examining the regulation of mitochondrial dynamics and biogenesis in healthy and diseased conditions. One approach to monitoring mitochondrial biogenesis is to measure the rate of mitochondrial DNA (mtDNA) replication. We developed a sensitive technique to visualize newly synthesized mtDNA in individual cells to study mtDNA replication within subcellular compartments of neurons. The technique combines the incorporation of 5-bromo-2-deoxyuridine (BrdU) and/or 5-ethynyl-2'-deoxyuridine (EdU) into mtDNA, together with a tyramide signal amplification protocol. Employing this technique, we visualized and measured mtDNA biogenesis in individual cells. The labeling procedure for EdU allows for more comprehensive results by allowing the comparison of its incorporation with other intracellular markers, because it does not require the harsh acid or enzyme digests necessary to recover the BrdU epitope. In addition, the utilization of both BrdU and EdU permits sequential pulse-chase experiments to follow the intracellular localization of mtDNA replication. The ability to quantify mitochondrial biogenesis provides an essential tool for investigating the alterations in mitochondrial dynamics involved in the pathogenesis of multiple cellular disorders, including neuropathies and neurodegenerative diseases.

  11. Dynamics of Cytoplasmic Incompatibility and Mtdna Variation in Natural Drosophila Simulans Populations

    PubMed Central

    Turelli, M.; Hoffmann, A. A.; McKechnie, S. W.

    1992-01-01

    In Drosophila simulans a cytoplasmically transmitted microorganism causes reduced egg hatch when infected males mate with uninfected females. The infection is rapidly spreading northward in California. Data on a specific mtDNA restriction site length polymorphism show that changes in the frequency of mtDNA variants are associated with this spread. All infected flies possess the same mtDNA allele, whereas the uninfected flies are polymorphic. Given that both paternal inheritance of the infection and imperfect maternal transmission have been demonstrated, one might expect instead that both infected and uninfected flies would possess both mtDNA variants. Our data suggest that imperfect female transmission of the infection (and/or the loss of the infection among progeny) is more common in nature than paternal transmission. A simple model of intrapopulation dynamics, with empirically supported parameter values, adequately describes the joint frequencies of the mtDNA variants and incompatibility types. PMID:1468627

  12. No consistent evidence for association between mtDNA variants and Alzheimer disease

    PubMed Central

    Hudson, G.; Sims, R.; Harold, D.; Chapman, J.; Hollingworth, P.; Gerrish, A.; Russo, G.; Hamshere, M.; Moskvina, V.; Jones, N.; Thomas, C.; Stretton, A.; Holmans, P.A.; O'Donovan, M.C.; Owen, M.J.; Williams, J.; Harold, Denise; Abraham, Richard; Hollingworth, Paul; Sims, Rebecca; Gerrish, Amy; Chapman, Jade; Russo, Giancarlo; Hamshere, Marian; Pahwa, Jaspreet Singh; Moskvina, Valentina; Dowzell, Kimberley; Williams, Amy; Jones, Nicola; Thomas, Charlene; Stretton, Alexandra; Morgan, Angharad; Lovestone, Simon; Powell, John; Proitsi, Petroula; Lupton, Michelle K; Brayne, Carol; Rubinsztein, David C.; Gill, Michael; Lawlor, Brian; Lynch, Aoibhinn; Morgan, Kevin; Brown, Kristelle; Passmore, Peter; Craig, David; McGuinness, Bernadette; Todd, Stephen; Johnston, Janet; Holmes, Clive; Mann, David; Smith, A. David; Love, Seth; Kehoe, Patrick G.; Hardy, John; Mead, Simon; Fox, Nick; Rossor, Martin; Collinge, John; Maier, Wolfgang; Jessen, Frank; Heun, Reiner; Kölsch, Heike; Schürmann, Britta; van den Bussche, Hendrik; Heuser, Isabella; Kornhuber, Johannes; Wiltfang, Jens; Dichgans, Martin; Frölich, Lutz; Hampel, Harald; Hüll, Michael; Rujescu, Dan; Goate, Alison; Kauwe, John S.K.; Cruchaga, Carlos; Nowotny, Petra; Morris, John C.; Mayo, Kevin; Livingston, Gill; Bass, Nicholas J.; Gurling, Hugh; McQuillin, Andrew; Gwilliam, Rhian; Deloukas, Panagiotis; Holmans, Peter; O'Donovan, Michael; Owen, Michael J.; Williams, Julie

    2012-01-01

    Objective: Although several studies have described an association between Alzheimer disease (AD) and genetic variation of mitochondrial DNA (mtDNA), each has implicated different mtDNA variants, so the role of mtDNA in the etiology of AD remains uncertain. Methods: We tested 138 mtDNA variants for association with AD in a powerful sample of 4,133 AD case patients and 1,602 matched controls from 3 Caucasian populations. Of the total population, 3,250 case patients and 1,221 elderly controls met the quality control criteria and were included in the analysis. Results: In the largest study to date, we failed to replicate the published findings. Meta-analysis of the available data showed no evidence of an association with AD. Conclusion: The current evidence linking common mtDNA variations with AD is not compelling. PMID:22442439

  13. Geographic patterns of mtDNA diversity in Europe.

    PubMed

    Simoni, L; Calafell, F; Pettener, D; Bertranpetit, J; Barbujani, G

    2000-01-01

    Genetic diversity in Europe has been interpreted as a reflection of phenomena occurring during the Paleolithic ( approximately 45,000 years before the present [BP]), Mesolithic ( approximately 18,000 years BP), and Neolithic ( approximately 10,000 years BP) periods. A crucial role of the Neolithic demographic transition is supported by the analysis of most nuclear loci, but the interpretation of mtDNA evidence is controversial. More than 2,600 sequences of the first hypervariable mitochondrial control region were analyzed for geographic patterns in samples from Europe, the Near East, and the Caucasus. Two autocorrelation statistics were used, one based on allele-frequency differences between samples and the other based on both sequence and frequency differences between alleles. In the global analysis, limited geographic patterning was observed, which could largely be attributed to a marked difference between the Saami and all other populations. The distribution of the zones of highest mitochondrial variation (genetic boundaries) confirmed that the Saami are sharply differentiated from an otherwise rather homogeneous set of European samples. However, an area of significant clinal variation was identified around the Mediterranean Sea (and not in the north), even though the differences between northern and southern populations were insignificant. Both a Paleolithic expansion and the Neolithic demic diffusion of farmers could have determined a longitudinal cline of mtDNA diversity. However, additional phenomena must be considered in both models, to account both for the north-south differences and for the greater geographic scope of clinical patterns at nuclear loci. Conversely, two predicted consequences of models of Mesolithic reexpansion from glacial refugia were not observed in the present study.

  14. Geographic Patterns of mtDNA Diversity in Europe

    PubMed Central

    Simoni, Lucia; Calafell, Francesc; Pettener, Davide; Bertranpetit, Jaume; Barbujani, Guido

    2000-01-01

    Summary Genetic diversity in Europe has been interpreted as a reflection of phenomena occurring during the Paleolithic (∼45,000 years before the present [BP]), Mesolithic (∼18,000 years BP), and Neolithic (∼10,000 years BP) periods. A crucial role of the Neolithic demographic transition is supported by the analysis of most nuclear loci, but the interpretation of mtDNA evidence is controversial. More than 2,600 sequences of the first hypervariable mitochondrial control region were analyzed for geographic patterns in samples from Europe, the Near East, and the Caucasus. Two autocorrelation statistics were used, one based on allele-frequency differences between samples and the other based on both sequence and frequency differences between alleles. In the global analysis, limited geographic patterning was observed, which could largely be attributed to a marked difference between the Saami and all other populations. The distribution of the zones of highest mitochondrial variation (genetic boundaries) confirmed that the Saami are sharply differentiated from an otherwise rather homogeneous set of European samples. However, an area of significant clinal variation was identified around the Mediterranean Sea (and not in the north), even though the differences between northern and southern populations were insignificant. Both a Paleolithic expansion and the Neolithic demic diffusion of farmers could have determined a longitudinal cline of mtDNA diversity. However, additional phenomena must be considered in both models, to account both for the north-south differences and for the greater geographic scope of clinal patterns at nuclear loci. Conversely, two predicted consequences of models of Mesolithic reexpansion from glacial refugia were not observed in the present study. PMID:10631156

  15. The Effects of Natural Hybridization on the Regulation of Doubly Uniparental Mtdna Inheritance in Blue Mussels (Mytilus Spp.)

    PubMed Central

    Rawson, P. D.; Secor, C. L.; Hilbish, T. J.

    1996-01-01

    Blue mussels in the Mytilus edulis species complex have a doubly uniparental mode of mtDNA inheritance with separate maternal and paternal mtDNA lineages. Female mussels inherit their mtDNA solely from their mother, while males inherit mtDNA from both parents. In the male gonad the paternal mtDNA is preferentially replicated so that only paternal mtDNA is transmitted from fathers to sons. Hybridization is common among differentiated blue mussel taxa; whenever it involves M. trossulus, doubly uniparental mtDNA inheritance is disrupted. We have found high frequencies of males without and females with paternal mtDNA among hybrid mussels produced by interspecific matings between M. galloprovincialis and M. trossulus. In contrast, hybridization between M. galloprovincialis and M. edulis does not affect doubly uniparental inheritance, indicating a difference in the divergence of the mechanisms regulating mtDNA inheritance among the three blue mussel taxa. Our data indicate a high frequency of disrupted mtDNA transmission in F(1) hybrids and suggest that two separate mechanisms, one regulating the transmission of paternal mtDNA to males and another inhibiting the establishment of paternal mtDNA in females, act to regulate doubly uniparental inheritance. We propose a model for the regulation of doubly uniparental inheritance that is consistent with these observations. PMID:8878689

  16. Extensive paternal mtDNA leakage in natural populations of Drosophila melanogaster

    PubMed Central

    Nunes, Maria D S; Dolezal, Marlies; Schlötterer, Christian

    2013-01-01

    Strict maternal inheritance is considered a hallmark of animal mtDNA. Although recent reports suggest that paternal leakage occurs in a broad range of species, it is still considered an exceptionally rare event. To evaluate the impact of paternal leakage on the evolution of mtDNA, it is essential to reliably estimate the frequency of paternal leakage in natural populations. Using allele-specific real-time quantitative PCR (RT-qPCR), we show that heteroplasmy is common in natural populations with at least 14% of the individuals carrying multiple mitochondrial haplotypes. However, the average frequency of the minor mtDNA haplotype is low (0.8%), which suggests that this pervasive heteroplasmy has not been noticed before due to a lack of power in sequencing surveys. Based on the distribution of mtDNA haplotypes in the offspring of heteroplasmic mothers, we found no evidence for strong selection against one of the haplotypes. We estimated that the rate of paternal leakage is 6% and that at least 100 generations are required for complete sorting of mtDNA haplotypes. Despite the high proportion of heteroplasmic individuals in natural populations, we found no evidence for recombination between mtDNA molecules, suggesting that either recombination is rare or recombinant haplotypes are counter-selected. Our results indicate that evolutionary studies using mtDNA as a marker might be biased by paternal leakage in this species. PMID:23452233

  17. mtDNA Mutations and Their Role in Aging, Diseases and Forensic Sciences.

    PubMed

    Zapico, Sara C; Ubelaker, Douglas H

    2013-10-03

    Mitochondria are independent organelles with their own DNA. As a primary function, mitochondria produce the energy for the cell through Oxidative Phosphorylation (OXPHOS) in the Electron Transport Chain (ETC). One of the toxic products of this process is Reactive Oxygen Species (ROS), which can induce oxidative damage in macromolecules like lipids, proteins and DNA. Mitochondrial DNA (mtDNA) is less protected and has fewer reparation mechanisms than nuclear DNA (nDNA), and as such is more exposed to oxidative, mutation-inducing damage. This review analyzes the causes and consequences of mtDNA mutations and their relationship with the aging process. Neurodegenerative diseases, related with the aging, are consequences of mtDNA mutations resulting in a decrease in mitochondrial function. Also described are "mitochondrial diseases", pathologies produced by mtDNA mutations and whose symptoms are related with mitochondrial dysfunction. Finally, mtDNA haplogroups are defined in this review; these groups are important for determination of geographical origin of an individual. Additionally, different haplogroups exhibit variably longevity and risk of certain diseases. mtDNA mutations in aging and haplogroups are of special interest to forensic science research. Therefore this review will help to clarify the key role of mtDNA mutations in these processes and support further research in this area.

  18. mtDNA Mutations and Their Role in Aging, Diseases and Forensic Sciences

    PubMed Central

    Zapico, Sara C.; Ubelaker, Douglas H.

    2013-01-01

    Mitochondria are independent organelles with their own DNA. As a primary function, mitochondria produce the energy for the cell through Oxidative Phosphorylation (OXPHOS) in the Electron Transport Chain (ETC). One of the toxic products of this process is Reactive Oxygen Species (ROS), which can induce oxidative damage in macromolecules like lipids, proteins and DNA. Mitochondrial DNA (mtDNA) is less protected and has fewer reparation mechanisms than nuclear DNA (nDNA), and as such is more exposed to oxidative, mutation-inducing damage. This review analyzes the causes and consequences of mtDNA mutations and their relationship with the aging process. Neurodegenerative diseases, related with the aging, are consequences of mtDNA mutations resulting in a decrease in mitochondrial function. Also described are “mitochondrial diseases”, pathologies produced by mtDNA mutations and whose symptoms are related with mitochondrial dysfunction. Finally, mtDNA haplogroups are defined in this review; these groups are important for determination of geographical origin of an individual. Additionally, different haplogroups exhibit variably longevity and risk of certain diseases. mtDNA mutations in aging and haplogroups are of special interest to forensic science research. Therefore this review will help to clarify the key role of mtDNA mutations in these processes and support further research in this area. PMID:24307969

  19. mtDNA Variation among Greenland Eskimos: The Edge of theBeringian Expansion

    PubMed Central

    Saillard, Juliette; Forster, Peter; Lynnerup, Niels; Bandelt, Hans-Jürgen; Nørby, Søren

    2000-01-01

    The Eskimo-Aleut language phylum is distributed from coastal Siberia across Alaska and Canada to Greenland and is well distinguished from the neighboring Na Dene languages. Genetically, however, the distinction between Na Dene and Eskimo-Aleut speakers is less clear. In order to improve the genetic characterization of Eskimos in general and Greenlanders in particular, we have sequenced hypervariable segment I (HVS-I) of the mitochondrial DNA (mtDNA) control region and typed relevant RFLP sites in the mtDNA of 82 Eskimos from Greenland. A comparison of our data with published sequences demonstrates major mtDNA types shared between Na Dene and Eskimo, indicating a common Beringian history within the Holocene. We further confirm the presence of an Eskimo-specific mtDNA subgroup characterized by nucleotide position 16265G within mtDNA group A2. This subgroup is found in all Eskimo groups analyzed so far and is estimated to have originated <3,000 years ago. A founder analysis of all Eskimo and Chukchi A2 types indicates that the Siberian and Greenland ancestral mtDNA pools separated around the time when the Neo-Eskimo culture emerged. The Greenland mtDNA types are a subset of the Alaskan mtDNA variation: they lack the groups D2 and D3 found in Siberia and Alaska and are exclusively A2 but at the same time lack the A2 root type. The data are in agreement with the view that the present Greenland Eskimos essentially descend from Alaskan Neo-Eskimos. European mtDNA types are absent in our Eskimo sample. PMID:10924403

  20. African human mtDNA phylogeography at-a-glance.

    PubMed

    Rosa, Alexandra; Brehem, António

    2011-01-01

    The mitochondrial DNA (mtDNA) genetic system has long proven to be useful for studying the demographic history of our species, since their proposed Southeast/East African origin 200 kya. Despite the weak archaeological and anthropologic records, which render a difficult understanding of early intra- continental migrations, the phylogenetic L0-L1'6 split at about 140-160 kya is thought to represent also an early sub-structuring of small and isolated communities in South and East Africa. Regional variation accumulated over the following millennia, with L2 and L3 lineages arising in Central and East Africa 100-75 kya. Their sub-Saharan dispersal not later than 60 kya, largely overwhelmed the L0'1 distribution, nowadays limited to South African Khoisan and Central African Pygmies. Cyclic expansions and retractions of the equatorial forest between 40 kya and the "Last Glacial Aridity Maximum" were able to reduce the genetic diversity of modern humans. Surviving regional-specific lineages have emerged from the Sahelian refuge areas, repopulating the region and contributing to the overall West African genetic similarity. Particular L1- L3 lineages mirror the substantial population growth made possible by moister and warmer conditions of the Sahara's Wet Phase and the adoption of agriculture and iron smelting techniques. The diffusion of the farming expertise from a Central African source towards South Africa was mediated by the Bantu people 3 kya. The strong impact of their gene flow almost erased the pre-existent maternal pool. Non-L mtDNAs testify for Eurasian lineages that have enriched the African maternal pool at different timeframes: i) Near and Middle Eastern influences in Upper Palaeolithic, probably link to the spread of Afro-Asiatic languages; ii) particular lineages from West Eurasia around or after the glacial period; iii) post-glacial mtDNA signatures from the Franco-Cantabrian refugia, that have crossed the Strait of Gibraltar and iv) Eurasian lineages

  1. Addressing RNA integrity to determine the impact of mitochondrial DNA mutations on brain mitochondrial function with age.

    PubMed

    Wang, Wei; Scheffler, Katja; Esbensen, Ying; Strand, Janne M; Stewart, James B; Bjørås, Magnar; Eide, Lars

    2014-01-01

    Mitochondrial DNA (mtDNA) mutations can result in mitochondrial dysfunction, but emerging experimental data question the fundamental role of mtDNA mutagenesis in age-associated mitochondrial impairment. The multicopy nature of mtDNA renders the impact of a given mtDNA mutation unpredictable. In this study, we compared mtDNA stability and mtRNA integrity during normal aging. Seven distinct sites in mouse brain mtDNA and corresponding mtRNA were analyzed. Accumulation of mtDNA mutations during aging was highly site-specific. The variation in mutation frequencies overrode the age-mediated increase by more than 100-fold and aging generally did not influence mtDNA mutagenesis. Errors introduced by mtRNA polymerase were also site-dependent and up to two hundred-fold more frequent than mtDNA mutations, and independent of mtDNA mutation frequency. We therefore conclude that mitochondrial transcription fidelity limits the impact of mtDNA mutations.

  2. Addressing RNA Integrity to Determine the Impact of Mitochondrial DNA Mutations on Brain Mitochondrial Function with Age

    PubMed Central

    Wang, Wei; Scheffler, Katja; Esbensen, Ying; Strand, Janne M.; Stewart, James B.; Bjørås, Magnar; Eide, Lars

    2014-01-01

    Mitochondrial DNA (mtDNA) mutations can result in mitochondrial dysfunction, but emerging experimental data question the fundamental role of mtDNA mutagenesis in age-associated mitochondrial impairment. The multicopy nature of mtDNA renders the impact of a given mtDNA mutation unpredictable. In this study, we compared mtDNA stability and mtRNA integrity during normal aging. Seven distinct sites in mouse brain mtDNA and corresponding mtRNA were analyzed. Accumulation of mtDNA mutations during aging was highly site-specific. The variation in mutation frequencies overrode the age-mediated increase by more than 100-fold and aging generally did not influence mtDNA mutagenesis. Errors introduced by mtRNA polymerase were also site-dependent and up to two hundred-fold more frequent than mtDNA mutations, and independent of mtDNA mutation frequency. We therefore conclude that mitochondrial transcription fidelity limits the impact of mtDNA mutations. PMID:24819950

  3. Mitochondrial DNA (mtDNA) haplogroups in 1526 unrelated individuals from 11 Departments of Colombia

    PubMed Central

    Yunis, Juan J.; Yunis, Emilio J.

    2013-01-01

    The frequencies of four mitochondrial Native American DNA haplogroups were determined in 1526 unrelated individuals from 11 Departments of Colombia and compared to the frequencies previously obtained for Amerindian and Afro-Colombian populations. Amerindian mtDNA haplogroups ranged from 74% to 97%. The lowest frequencies were found in Departments on the Caribbean coast and in the Pacific region, where the frequency of Afro-Colombians is higher, while the highest mtDNA Amerindian haplogroup frequencies were found in Departments that historically have a strong Amerindian heritage. Interestingly, all four mtDNA haplogroups were found in all Departments, in contrast to the complete absence of haplogroup D and high frequencies of haplogroup A in Amerindian populations in the Caribbean region of Colombia. Our results indicate that all four Native American mtDNA haplogroups were widely distributed in Colombia at the time of the Spanish conquest. PMID:24130438

  4. Mitochondrial DNA (mtDNA) haplogroups in 1526 unrelated individuals from 11 Departments of Colombia.

    PubMed

    Yunis, Juan J; Yunis, Emilio J

    2013-09-01

    The frequencies of four mitochondrial Native American DNA haplogroups were determined in 1526 unrelated individuals from 11 Departments of Colombia and compared to the frequencies previously obtained for Amerindian and Afro-Colombian populations. Amerindian mtDNA haplogroups ranged from 74% to 97%. The lowest frequencies were found in Departments on the Caribbean coast and in the Pacific region, where the frequency of Afro-Colombians is higher, while the highest mtDNA Amerindian haplogroup frequencies were found in Departments that historically have a strong Amerindian heritage. Interestingly, all four mtDNA haplogroups were found in all Departments, in contrast to the complete absence of haplogroup D and high frequencies of haplogroup A in Amerindian populations in the Caribbean region of Colombia. Our results indicate that all four Native American mtDNA haplogroups were widely distributed in Colombia at the time of the Spanish conquest.

  5. Searching for doubly uniparental inheritance of mtDNA in the apple snail Pomacea diffusa.

    PubMed

    Parakatselaki, Maria Eleni; Saavedra, Carlos; Ladoukakis, Emmanuel D

    2016-11-01

    Doubly uniparental inheritance (DUI) of mitochondrial DNA (mtDNA) is an exceptional mode of mtDNA transmission, restricted so far to the class of bivalves. We searched for DUI outside bivalves using the apple snail Pomacea diffusa. It was an appropriate candidate to search for DUI for three reasons; it belongs to gastropods, which is the closest sister group to bivalves, it is gonochoristic and it has a strong sex bias in the progeny of different female individuals. These phenomena (gonochorism and sex-biased progeny) are also found in species with DUI. We searched for heteroplasmy in males and for high sequence divergence among mtDNA sequences obtained from male and female gonads. All sequences examined were identical. These data suggest that the mtDNA in P. diffusa is maternally transmitted and DUI remains an exclusive characteristic of bivalves.

  6. Leber Hereditary Optic Neuropathy: Exemplar of an mtDNA Disease.

    PubMed

    Wallace, Douglas C; Lott, Marie T

    2017-02-24

    The report in 1988 that Leber Hereditary Optic Neuropathy (LHON) was the product of mitochondrial DNA (mtDNA) mutations provided the first demonstration of the clinical relevance of inherited mtDNA variation. From LHON studies, the medical importance was demonstrated for the mtDNA showing its coding for the most important energy genes, its maternal inheritance, its high mutation rate, its presence in hundreds to thousands of copies per cell, its quantitatively segregation of biallelic genotypes during both mitosis and meiosis, its preferential effect on the most energetic tissues including the eye and brain, its wide range of functional polymorphisms that predispose to common diseases, and its accumulation of mutations within somatic tissues providing the aging clock. These features of mtDNA genetics, in combination with the genetics of the 1-2000 nuclear DNA (nDNA) coded mitochondrial genes, is not only explaining the genetics of LHON but also providing a model for understanding the complexity of many common diseases. With the maturation of LHON biology and genetics, novel animal models for complex disease have been developed and new therapeutic targets and strategies envisioned, both pharmacological and genetic. Multiple somatic gene therapy approaches are being developed for LHON which are applicable to other mtDNA diseases. Moreover, the unique cytoplasmic genetics of the mtDNA has permitted the first successful human germline gene therapy via spindle nDNA transfer from mtDNA mutant oocytes to enucleated normal mtDNA oocytes. Such LHON lessons are actively being applied to common ophthalmological diseases like glaucoma and neurological diseases like Parkinsonism.

  7. How Good Are Indirect Tests at Detecting Recombination in Human mtDNA?

    PubMed Central

    White, Daniel James; Bryant, David; Gemmell, Neil John

    2013-01-01

    Empirical proof of human mitochondrial DNA (mtDNA) recombination in somatic tissues was obtained in 2004; however, a lack of irrefutable evidence exists for recombination in human mtDNA at the population level. Our inability to demonstrate convincingly a signal of recombination in population data sets of human mtDNA sequence may be due, in part, to the ineffectiveness of current indirect tests. Previously, we tested some well-established indirect tests of recombination (linkage disequilibrium vs. distance using D′ and r2, Homoplasy Test, Pairwise Homoplasy Index, Neighborhood Similarity Score, and Max χ2) on sequence data derived from the only empirically confirmed case of human mtDNA recombination thus far and demonstrated that some methods were unable to detect recombination. Here, we assess the performance of these six well-established tests and explore what characteristics specific to human mtDNA sequence may affect their efficacy by simulating sequence under various parameters with levels of recombination (ρ) that vary around an empirically derived estimate for human mtDNA (population parameter ρ = 5.492). No test performed infallibly under any of our scenarios, and error rates varied across tests, whereas detection rates increased substantially with ρ values > 5.492. Under a model of evolution that incorporates parameters specific to human mtDNA, including rate heterogeneity, population expansion, and ρ = 5.492, successful detection rates are limited to a range of 7−70% across tests with an acceptable level of false-positive results: the neighborhood similarity score incompatibility test performed best overall under these parameters. Population growth seems to have the greatest impact on recombination detection probabilities across all models tested, likely due to its impact on sequence diversity. The implications of our findings on our current understanding of mtDNA recombination in humans are discussed. PMID:23665874

  8. MtDNA depleted PC3 cells exhibit Warburg effect and cancer stem cell features

    PubMed Central

    Li, Xiaoran; Zhong, Yali; Lu, Jie; Axcrona, Karol; Eide, Lars; Syljuåsen, Randi G.; Peng, Qian; Wang, Junbai; Zhang, Hongquan; Goscinski, Mariusz Adam; Kvalheim, Gunnar; Nesland, Jahn M.; Suo, Zhenhe

    2016-01-01

    Reducing mtDNA content was considered as a critical step in the metabolism restructuring for cell stemness restoration and further neoplastic development. However, the connections between mtDNA depletion and metabolism reprograming-based cancer cell stemness in prostate cancers are still lack of studies. Here, we demonstrated that human CRPC cell line PC3 tolerated high concentration of the mtDNA replication inhibitor ethidium bromide (EtBr) and the mtDNA depletion triggered a universal metabolic remodeling process. Failure in completing that process caused lethal consequences. The mtDNA depleted (MtDP) PC3 cells could be steadily maintained in the special medium in slow cycling status. The MtDP PC3 cells contained immature mitochondria and exhibited Warburg effect. Furthermore, the MtDP PC3 cells were resistant to therapeutic treatments and contained greater cancer stem cell-like subpopulations: CD44+, ABCG2+, side-population and ALDHbright. In conclusion, these results highlight the association of mtDNA content, mitochondrial function and cancer cell stemness features. PMID:27248169

  9. Impaired dynamics and function of mitochondria caused by mtDNA toxicity leads to heart failure.

    PubMed

    Lauritzen, Knut H; Kleppa, Liv; Aronsen, Jan Magnus; Eide, Lars; Carlsen, Harald; Haugen, Øyvind P; Sjaastad, Ivar; Klungland, Arne; Rasmussen, Lene Juel; Attramadal, Håvard; Storm-Mathisen, Jon; Bergersen, Linda H

    2015-08-01

    Cardiac mitochondrial dysfunction has been implicated in heart failure of diverse etiologies. Generalized mitochondrial disease also leads to cardiomyopathy with various clinical manifestations. Impaired mitochondrial homeostasis may over time, such as in the aging heart, lead to cardiac dysfunction. Mitochondrial DNA (mtDNA), close to the electron transport chain and unprotected by histones, may be a primary pathogenetic site, but this is not known. Here, we test the hypothesis that cumulative damage of cardiomyocyte mtDNA leads to cardiomyopathy and heart failure. Transgenic mice with Tet-on inducible, cardiomyocyte-specific expression of a mutant uracil-DNA glycosylase 1 (mutUNG1) were generated. The mutUNG1 is known to remove thymine in addition to uracil from the mitochondrial genome, generating apyrimidinic sites, which obstruct mtDNA function. Following induction of mutUNG1 in cardiac myocytes by administering doxycycline, the mice developed hypertrophic cardiomyopathy, leading to congestive heart failure and premature death after ∼2 mo. The heart showed reduced mtDNA replication, severely diminished mtDNA transcription, and suppressed mitochondrial respiration with increased Pgc-1α, mitochondrial mass, and antioxidative defense enzymes, and finally failing mitochondrial fission/fusion dynamics and deteriorating myocardial contractility as the mechanism of heart failure. The approach provides a model with induced cardiac-restricted mtDNA damage for investigation of mtDNA-based heart disease.

  10. TP53 codon 72 polymorphism affects accumulation of mtDNA damage in human cells

    PubMed Central

    Altilia, Serena; Santoro, Aurelia; Malagoli, Davide; Lanzarini, Catia; Álvarez, Josué Adolfo Ballesteros; Galazzo, Gianluca; Porter, Donald Carl; Crocco, Paolina; Rose, Giuseppina; Passarino, Giuseppe; Roninson, Igor Boris; Franceschi, Claudio; Salvioli, Stefano

    2012-01-01

    Human TP53 gene is characterised by a polymorphism at codon 72 leading to an Arginine-to-Proline (R/P) substitution. The two resulting p53 isoforms have a different subcellular localisation after stress (more nuclear or more mitochondrial for the P or R isoform, respectively). p53P72 variant is more efficient than p53R72 in inducing the expression of genes involved in nuclear DNA repair. Since p53 is involved also in mitochondrial DNA (mtDNA) maintenance, we wondered whether these p53 isoforms are associated with different accumulation of mtDNA damage. We observed that cells bearing p53R72 accumulate lower amount of mtDNA damage upon rotenone stress with respect to cells bearing p53P72, and that p53R72 co-localises with polymerase gamma more than p53P72. We also analysed the in vivo accumulation of heteroplasmy in a 300 bp fragment of mtDNA D-loop of 425 aged subjects. We observed that subjects with heteroplasmy higher than 5% are significantly less than expected in the p53R72/R72 group. On the whole, these data suggest that the polymorphism of TP53 at codon 72 affects the accumulation of mtDNA mutations, likely through the different ability of the two p53 isoforms to bind to polymerase gamma, and may contribute to in vivo accumulation of mtDNA mutations. PMID:22289634

  11. The occurrence of mtDNA heteroplasmy in multiple cetacean species.

    PubMed

    Vollmer, Nicole L; Viricel, Amélia; Wilcox, Lynsey; Katherine Moore, M; Rosel, Patricia E

    2011-04-01

    In population genetics and phylogenetic studies, mitochondrial DNA (mtDNA) is commonly used for examining differences both between and within groups of individuals. For these studies, correct interpretation of every nucleotide position is crucial but can be complicated by the presence of ambiguous bases resulting from heteroplasmy. Particularly for non-model taxa, the presence of heteroplasmy in mtDNA is rarely reported, therefore, it is unclear how commonly it occurs and how it can affect phylogenetic relationships among taxa and the overall understanding of evolutionary processes. We examined the occurrence of both site and length heteroplasmy within the mtDNA of ten marine mammal species, for most of which mtDNA heteroplasmy has never been reported. After sequencing a portion of the mtDNA control region for 5,062 individuals, we found heteroplasmy in at least 2% of individuals from seven species, including Stenella frontalis where 58.9% were heteroplasmic. We verified the presence of true heteroplasmy, ruling out artifacts from amplification and sequencing methods and the presence of nuclear copies of mitochondrial genes. We found no evidence that mtDNA heteroplasmy influenced phylogenetic relationships, however, its occurrence does have the potential to increase the genetic diversity for all species in which it is found. This study stresses the importance of both detecting and reporting the occurrence of heteroplasmy in wild populations in order to enhance the knowledge of both the introduction and the persistence of mutant mitochondrial haplotypes in the evolutionary process.

  12. Random mtDNA mutations modulate proliferation capacity in mouse embryonic fibroblasts

    SciTech Connect

    Kukat, Alexandra; Edgar, Daniel; Bratic, Ivana; Maiti, Priyanka; Trifunovic, Aleksandra

    2011-06-10

    Highlights: {yields} Increased mtDNA mutations in MEFs lead to high level of spontaneous immortalization. {yields} This process is independent of endogenous ROS production. {yields} Aerobic glycolysis significantly contributes to spontaneous immortalization of MEFs. -- Abstract: An increase in mtDNA mutation load leads to a loss of critical cells in different tissues thereby contributing to the physiological process of organismal ageing. Additionally, the accumulation of senescent cells that display changes in metabolic function might act in an active way to further disrupt the normal tissue function. We believe that this could be the important link missing in our understanding of the molecular mechanisms of premature ageing in the mtDNA mutator mice. We tested proliferation capacity of mtDNA mutator cells in vitro. When cultured in physiological levels of oxygen (3%) their proliferation capacity is somewhat lower than wild-type cells. Surprisingly, in conditions of increased oxidative stress (20% O{sub 2}) mtDNA mutator mouse embryonic fibroblasts exhibit continuous proliferation due to spontaneous immortalization, whereas the same conditions promote senescence in wild-type cells. We believe that an increase in aerobic glycolysis observed in mtDNA mutator mice is a major mechanism behind this process. We propose that glycolysis promotes proliferation and allows a fast turnover of metabolites, but also leads to energy crisis due to lower ATP production rate. This could lead to compromised replication and/or repair and therefore, in rare cases, might lead to mutations in tumor suppressor genes and spontaneous immortalization.

  13. The a2 Mating-Type Locus Genes lga2 and rga2 Direct Uniparental Mitochondrial DNA (mtDNA) Inheritance and Constrain mtDNA Recombination During Sexual Development of Ustilago maydis

    PubMed Central

    Fedler, Michael; Luh, Kai-Stephen; Stelter, Kathrin; Nieto-Jacobo, Fernanda; Basse, Christoph W.

    2009-01-01

    Uniparental inheritance of mitochondria dominates among sexual eukaryotes. However, little is known about the mechanisms and genetic determinants. We have investigated the role of the plant pathogen Ustilago maydis genes lga2 and rga2 in uniparental mitochondrial DNA (mtDNA) inheritance during sexual development. The lga2 and rga2 genes are specific to the a2 mating-type locus and encode small mitochondrial proteins. On the basis of identified sequence polymorphisms due to variable intron numbers in mitochondrial genotypes, we could demonstrate that lga2 and rga2 decisively influence mtDNA inheritance in matings between a1 and a2 strains. Deletion of lga2 favored biparental inheritance and generation of recombinant mtDNA molecules in combinations in which inheritance of mtDNA of the a2 partner dominated. Conversely, deletion of rga2 resulted in predominant loss of a2-specific mtDNA and favored inheritance of the a1 mtDNA. Furthermore, expression of rga2 in the a1 partner protected the associated mtDNA from elimination. Our results indicate that Lga2 in conjunction with Rga2 directs uniparental mtDNA inheritance by mediating loss of the a1-associated mtDNA. This study shows for the first time an interplay of mitochondrial proteins in regulating uniparental mtDNA inheritance. PMID:19104076

  14. The a2 mating-type locus genes lga2 and rga2 direct uniparental mitochondrial DNA (mtDNA) inheritance and constrain mtDNA recombination during sexual development of Ustilago maydis.

    PubMed

    Fedler, Michael; Luh, Kai-Stephen; Stelter, Kathrin; Nieto-Jacobo, Fernanda; Basse, Christoph W

    2009-03-01

    Uniparental inheritance of mitochondria dominates among sexual eukaryotes. However, little is known about the mechanisms and genetic determinants. We have investigated the role of the plant pathogen Ustilago maydis genes lga2 and rga2 in uniparental mitochondrial DNA (mtDNA) inheritance during sexual development. The lga2 and rga2 genes are specific to the a2 mating-type locus and encode small mitochondrial proteins. On the basis of identified sequence polymorphisms due to variable intron numbers in mitochondrial genotypes, we could demonstrate that lga2 and rga2 decisively influence mtDNA inheritance in matings between a1 and a2 strains. Deletion of lga2 favored biparental inheritance and generation of recombinant mtDNA molecules in combinations in which inheritance of mtDNA of the a2 partner dominated. Conversely, deletion of rga2 resulted in predominant loss of a2-specific mtDNA and favored inheritance of the a1 mtDNA. Furthermore, expression of rga2 in the a1 partner protected the associated mtDNA from elimination. Our results indicate that Lga2 in conjunction with Rga2 directs uniparental mtDNA inheritance by mediating loss of the a1-associated mtDNA. This study shows for the first time an interplay of mitochondrial proteins in regulating uniparental mtDNA inheritance.

  15. Ancient mtDNA sequences from the First Australians revisited

    PubMed Central

    Subramanian, Sankar; Wright, Joanne L.; Endicott, Phillip; Westaway, Michael Carrington; Huynen, Leon; Parson, Walther; Millar, Craig D.; Willerslev, Eske; Lambert, David M.

    2016-01-01

    The publication in 2001 by Adcock et al. [Adcock GJ, et al. (2001) Proc Natl Acad Sci USA 98(2):537–542] in PNAS reported the recovery of short mtDNA sequences from ancient Australians, including the 42,000-y-old Mungo Man [Willandra Lakes Hominid (WLH3)]. This landmark study in human ancient DNA suggested that an early modern human mitochondrial lineage emerged in Asia and that the theory of modern human origins could no longer be considered solely through the lens of the “Out of Africa” model. To evaluate these claims, we used second generation DNA sequencing and capture methods as well as PCR-based and single-primer extension (SPEX) approaches to reexamine the same four Willandra Lakes and Kow Swamp 8 (KS8) remains studied in the work by Adcock et al. Two of the remains sampled contained no identifiable human DNA (WLH15 and WLH55), whereas the Mungo Man (WLH3) sample contained no Aboriginal Australian DNA. KS8 reveals human mitochondrial sequences that differ from the previously inferred sequence. Instead, we recover a total of five modern European contaminants from Mungo Man (WLH3). We show that the remaining sample (WLH4) contains ∼1.4% human DNA, from which we assembled two complete mitochondrial genomes. One of these was a previously unidentified Aboriginal Australian haplotype belonging to haplogroup S2 that we sequenced to a high coverage. The other was a contaminating modern European mitochondrial haplotype. Although none of the sequences that we recovered matched those reported by Adcock et al., except a contaminant, these findings show the feasibility of obtaining important information from ancient Aboriginal Australian remains. PMID:27274055

  16. Ancient mtDNA sequences from the First Australians revisited.

    PubMed

    Heupink, Tim H; Subramanian, Sankar; Wright, Joanne L; Endicott, Phillip; Westaway, Michael Carrington; Huynen, Leon; Parson, Walther; Millar, Craig D; Willerslev, Eske; Lambert, David M

    2016-06-21

    The publication in 2001 by Adcock et al. [Adcock GJ, et al. (2001) Proc Natl Acad Sci USA 98(2):537-542] in PNAS reported the recovery of short mtDNA sequences from ancient Australians, including the 42,000-y-old Mungo Man [Willandra Lakes Hominid (WLH3)]. This landmark study in human ancient DNA suggested that an early modern human mitochondrial lineage emerged in Asia and that the theory of modern human origins could no longer be considered solely through the lens of the "Out of Africa" model. To evaluate these claims, we used second generation DNA sequencing and capture methods as well as PCR-based and single-primer extension (SPEX) approaches to reexamine the same four Willandra Lakes and Kow Swamp 8 (KS8) remains studied in the work by Adcock et al. Two of the remains sampled contained no identifiable human DNA (WLH15 and WLH55), whereas the Mungo Man (WLH3) sample contained no Aboriginal Australian DNA. KS8 reveals human mitochondrial sequences that differ from the previously inferred sequence. Instead, we recover a total of five modern European contaminants from Mungo Man (WLH3). We show that the remaining sample (WLH4) contains ∼1.4% human DNA, from which we assembled two complete mitochondrial genomes. One of these was a previously unidentified Aboriginal Australian haplotype belonging to haplogroup S2 that we sequenced to a high coverage. The other was a contaminating modern European mitochondrial haplotype. Although none of the sequences that we recovered matched those reported by Adcock et al., except a contaminant, these findings show the feasibility of obtaining important information from ancient Aboriginal Australian remains.

  17. Mitochondrial transcription terminator family members mTTF and mTerf5 have opposing roles in coordination of mtDNA synthesis.

    PubMed

    Jõers, Priit; Lewis, Samantha C; Fukuoh, Atsushi; Parhiala, Mikael; Ellilä, Simo; Holt, Ian J; Jacobs, Howard T

    2013-01-01

    All genomes require a system for avoidance or handling of collisions between the machineries of DNA replication and transcription. We have investigated the roles in this process of the mTERF (mitochondrial transcription termination factor) family members mTTF and mTerf5 in Drosophila melanogaster. The two mTTF binding sites in Drosophila mtDNA, which also bind mTerf5, were found to coincide with major sites of replication pausing. RNAi-mediated knockdown of either factor resulted in mtDNA depletion and developmental arrest. mTTF knockdown decreased site-specific replication pausing, but led to an increase in replication stalling and fork regression in broad zones around each mTTF binding site. Lagging-strand DNA synthesis was impaired, with extended RNA/DNA hybrid segments seen in replication intermediates. This was accompanied by the accumulation of recombination intermediates and nicked/broken mtDNA species. Conversely, mTerf5 knockdown led to enhanced replication pausing at mTTF binding sites, a decrease in fragile replication intermediates containing single-stranded segments, and the disappearance of species containing segments of RNA/DNA hybrid. These findings indicate an essential and previously undescribed role for proteins of the mTERF family in the integration of transcription and DNA replication, preventing unregulated collisions and facilitating productive interactions between the two machineries that are inferred to be essential for completion of lagging-strand DNA synthesis.

  18. High Pressure-Induced mtDNA Alterations in Retinal Ganglion Cells and Subsequent Apoptosis

    PubMed Central

    Zhang, Sheng-Hai; Gao, Feng-Juan; Sun, Zhong-Mou; Xu, Ping; Chen, Jun-Yi; Sun, Xing-Huai; Wu, Ji-Hong

    2016-01-01

    Purpose: Our previous study indicated that mitochondrial DNA (mtDNA) damage and mutations are crucial to the progressive loss of retinal ganglion cells (RGCs) in a glaucomatous rat model. In this study, we examined whether high pressure could directly cause mtDNA alterations and whether the latter could lead to mitochondrial dysfunction and RGC death. Methods: Primary cultured rat RGCs were exposed to 30 mm Hg of hydrostatic pressure (HP) for 12, 24, 48, 72, 96 and 120 h. mtDNA alterations and mtDNA repair/replication enzymes OGG1, MYH and polymerase gamma (POLG) expressions were also analyzed. The RGCs were then infected with a lentiviral small hairpin RNA (shRNA) expression vector targeting POLG (POLG-shRNA), and mtDNA alterations as well as mitochondrial function, including complex I/III activities and ATP production were subsequently studied at appropriate times. Finally, RGC apoptosis and the mitochondrial-apoptosis pathway-related protein cleaved caspase-3 were detected using a Terminal deoxynucleotidyl transferase dUTP nick end-labeling (TUNEL) assay and western blotting, respectively. Results: mtDNA damage was observed as early as 48 h after the exposure of RGCs to HP. At 120 h after HP, mtDNA damage and mutations significantly increased, reaching >40% and 4.8 ± 0.3-fold, respectively, compared with the control values. Twelve hours after HP, the expressions of OGG1, MYH and POLG mRNA in the RGCs were obviously increased 5.02 ± 0.6-fold (p < 0.01), 4.3 ± 0.2-fold (p < 0.05), and 0.8 ± 0.09-fold (p < 0.05). Western blot analysis showed that the protein levels of the three enzymes decreased at 72 and 120 h after HP (p < 0.05). After interference with POLG-shRNA, the mtDNA damage and mutations were significantly increased (p < 0.01), while complex I/III activities gradually decreased (p < 0.05). Corresponding decreases in membrane potential and ATP production appeared at 5 and 6 days after POLG-shRNA transfection respectively (p < 0.05). Increases in the

  19. POLRMT regulates the switch between replication primer formation and gene expression of mammalian mtDNA

    PubMed Central

    Kühl, Inge; Miranda, Maria; Posse, Viktor; Milenkovic, Dusanka; Mourier, Arnaud; Siira, Stefan J.; Bonekamp, Nina A.; Neumann, Ulla; Filipovska, Aleksandra; Polosa, Paola Loguercio; Gustafsson, Claes M.; Larsson, Nils-Göran

    2016-01-01

    Mitochondria are vital in providing cellular energy via their oxidative phosphorylation system, which requires the coordinated expression of genes encoded by both the nuclear and mitochondrial genomes (mtDNA). Transcription of the circular mammalian mtDNA depends on a single mitochondrial RNA polymerase (POLRMT). Although the transcription initiation process is well understood, it is debated whether POLRMT also serves as the primase for the initiation of mtDNA replication. In the nucleus, the RNA polymerases needed for gene expression have no such role. Conditional knockout of Polrmt in the heart results in severe mitochondrial dysfunction causing dilated cardiomyopathy in young mice. We further studied the molecular consequences of different expression levels of POLRMT and found that POLRMT is essential for primer synthesis to initiate mtDNA replication in vivo. Furthermore, transcription initiation for primer formation has priority over gene expression. Surprisingly, mitochondrial transcription factor A (TFAM) exists in an mtDNA-free pool in the Polrmt knockout mice. TFAM levels remain unchanged despite strong mtDNA depletion, and TFAM is thus protected from degradation of the AAA+ Lon protease in the absence of POLRMT. Last, we report that mitochondrial transcription elongation factor may compensate for a partial depletion of POLRMT in heterozygous Polrmt knockout mice, indicating a direct regulatory role of this factor in transcription. In conclusion, we present in vivo evidence that POLRMT has a key regulatory role in the replication of mammalian mtDNA and is part of a transcriptional mechanism that provides a switch between primer formation for mtDNA replication and mitochondrial gene expression. PMID:27532055

  20. Mic60/Mitofilin determines MICOS assembly essential for mitochondrial dynamics and mtDNA nucleoid organization

    PubMed Central

    Li, H; Ruan, Y; Zhang, K; Jian, F; Hu, C; Miao, L; Gong, L; Sun, L; Zhang, X; Chen, S; Chen, H; Liu, D; Song, Z

    2016-01-01

    The MICOS complex (mitochondrial contact site and cristae organizing system) is essential for mitochondrial inner membrane organization and mitochondrial membrane contacts, however, the molecular regulation of MICOS assembly and the physiological functions of MICOS in mammals remain obscure. Here, we report that Mic60/Mitofilin has a critical role in the MICOS assembly, which determines the mitochondrial morphology and mitochondrial DNA (mtDNA) organization. The downregulation of Mic60/Mitofilin or Mic19/CHCHD3 results in instability of other MICOS components, disassembly of MICOS complex and disorganized mitochondrial cristae. We show that there exists direct interaction between Mic60/Mitofilin and Mic19/CHCHD3, which is crucial for their stabilization in mammals. Importantly, we identified that the mitochondrial i-AAA protease Yme1L regulates Mic60/Mitofilin homeostasis. Impaired MICOS assembly causes the formation of 'giant mitochondria' because of dysregulated mitochondrial fusion and fission. Also, mtDNA nucleoids are disorganized and clustered in these giant mitochondria in which mtDNA transcription is attenuated because of remarkable downregulation of some key mtDNA nucleoid-associated proteins. Together, these findings demonstrate that Mic60/Mitofilin homeostasis regulated by Yme1L is central to the MICOS assembly, which is required for maintenance of mitochondrial morphology and organization of mtDNA nucleoids. PMID:26250910

  1. Inspecting close maternal relatedness: Towards better mtDNA population samples in forensic databases

    PubMed Central

    Bodner, Martin; Irwin, Jodi A.; Coble, Michael D.; Parson, Walther

    2011-01-01

    Reliable data are crucial for all research fields applying mitochondrial DNA (mtDNA) as a genetic marker. Quality control measures have been introduced to ensure the highest standards in sequence data generation, validation and a posteriori inspection. A phylogenetic alignment strategy has been widely accepted as a prerequisite for data comparability and database searches, for forensic applications, for reconstructions of human migrations and for correct interpretation of mtDNA mutations in medical genetics. There is continuing effort to enhance the number of worldwide population samples in order to contribute to a better understanding of human mtDNA variation. This has often lead to the analysis of convenience samples collected for other purposes, which might not meet the quality requirement of random sampling for mtDNA data sets. Here, we introduce an additional quality control means that deals with one aspect of this limitation: by combining autosomal short tandem repeat (STR) marker with mtDNA information, it helps to avoid the bias introduced by related individuals included in the same (small) sample. By STR analysis of individuals sharing their mitochondrial haplotype, pedigree construction and subsequent software-assisted calculation of likelihood ratios based on the allele frequencies found in the population, closely maternally related individuals can be identified and excluded. We also discuss scenarios that allow related individuals in the same set. An ideal population sample would be representative for its population: this new approach represents another contribution towards this goal. PMID:21067986

  2. Heteroplasmy of mouse mtDNA is genetically unstable and results in altered behavior and cognition.

    PubMed

    Sharpley, Mark S; Marciniak, Christine; Eckel-Mahan, Kristin; McManus, Meagan; Crimi, Marco; Waymire, Katrina; Lin, Chun Shi; Masubuchi, Satoru; Friend, Nicole; Koike, Maya; Chalkia, Dimitra; MacGregor, Grant; Sassone-Corsi, Paolo; Wallace, Douglas C

    2012-10-12

    Maternal inheritance of mtDNA is the rule in most animals, but the reasons for this pattern remain unclear. To investigate the consequence of overriding uniparental inheritance, we generated mice containing an admixture (heteroplasmy) of NZB and 129S6 mtDNAs in the presence of a congenic C57BL/6J nuclear background. Analysis of the segregation of the two mtDNAs across subsequent maternal generations revealed that proportion of NZB mtDNA was preferentially reduced. Ultimately, this segregation process produced NZB-129 heteroplasmic mice and their NZB or 129 mtDNA homoplasmic counterparts. Phenotypic comparison of these three mtDNA lines demonstrated that the NZB-129 heteroplasmic mice, but neither homoplasmic counterpart, had reduced activity, food intake, respiratory exchange ratio; accentuated stress response; and cognitive impairment. Therefore, admixture of two normal but different mouse mtDNAs can be genetically unstable and can produce adverse physiological effects, factors that may explain the advantage of uniparental inheritance of mtDNA.

  3. Interpretation guidelines of mtDNA control region sequence electropherograms in forensic genetics.

    PubMed

    Marquez, Manuel Crespillo

    2012-01-01

    Forensic mitochondrial DNA (mtDNA) analysis is a complementary technique to forensic nuclear DNA (nDNA) and trace evidence analysis. Its use has been accepted by the vast majority of courts of law around the world. However for the forensic community it is crucial to employ standardized methods and procedures to guaranty the quality of the results obtained in court. In this chapter, we describe the most important aspects regarding the interpretation and assessment of mtDNA analysis, and offer a simple guide which places particular emphasis on those aspects that can impact the final interpretation of the results. These include the criteria for authenticating a sequence excluding the contaminant origin, defining the quality of a sequence, editing procedure, alignment criteria for searching the databases, and the statistical evaluation of matches. It is not easy to establish a single guide to interpretation for mtDNA analysis; however, it is important to understand all variables that may in some way affect the final conclusion in the context of a forensic case. As a general rule, laboratories should be cautious before issuing the final conclusion of an mtDNA analysis, and consider any significant limitations regarding current understanding of specific aspects of the mtDNA molecule.

  4. Metformin Uniquely Prevents Thrombosis by Inhibiting Platelet Activation and mtDNA Release

    PubMed Central

    Xin, Guang; Wei, Zeliang; Ji, Chengjie; Zheng, Huajie; Gu, Jun; Ma, Limei; Huang, Wenfang; Morris-Natschke, Susan L.; Yeh, Jwu-Lai; Zhang, Rui; Qin, Chaoyi; Wen, Li; Xing, Zhihua; Cao, Yu; Xia, Qing; Lu, Yanrong; Li, Ke; Niu, Hai; Lee, Kuo-Hsiung; Huang, Wen

    2016-01-01

    Thrombosis and its complications are the leading cause of death in patients with diabetes. Metformin, a first-line therapy for type 2 diabetes, is the only drug demonstrated to reduce cardiovascular complications in diabetic patients. However, whether metformin can effectively prevent thrombosis and its potential mechanism of action is unknown. Here we show, metformin prevents both venous and arterial thrombosis with no significant prolonged bleeding time by inhibiting platelet activation and extracellular mitochondrial DNA (mtDNA) release. Specifically, metformin inhibits mitochondrial complex I and thereby protects mitochondrial function, reduces activated platelet-induced mitochondrial hyperpolarization, reactive oxygen species overload and associated membrane damage. In mitochondrial function assays designed to detect amounts of extracellular mtDNA, we found that metformin prevents mtDNA release. This study also demonstrated that mtDNA induces platelet activation through a DC-SIGN dependent pathway. Metformin exemplifies a promising new class of antiplatelet agents that are highly effective at inhibiting platelet activation by decreasing the release of free mtDNA, which induces platelet activation in a DC-SIGN-dependent manner. This study has established a novel therapeutic strategy and molecular target for thrombotic diseases, especially for thrombotic complications of diabetes mellitus. PMID:27805009

  5. Presequence-Independent Mitochondrial Import of DNA Ligase Facilitates Establishment of Cell Lines with Reduced mtDNA Copy Number.

    PubMed

    Spadafora, Domenico; Kozhukhar, Natalia; Alexeyev, Mikhail F

    2016-01-01

    Due to the essential role played by mitochondrial DNA (mtDNA) in cellular physiology and bioenergetics, methods for establishing cell lines with altered mtDNA content are of considerable interest. Here, we report evidence for the existence in mammalian cells of a novel, low- efficiency, presequence-independent pathway for mitochondrial protein import, which facilitates mitochondrial uptake of such proteins as Chlorella virus ligase (ChVlig) and Escherichia coli LigA. Mouse cells engineered to depend on this pathway for mitochondrial import of the LigA protein for mtDNA maintenance had severely (up to >90%) reduced mtDNA content. These observations were used to establish a method for the generation of mouse cell lines with reduced mtDNA copy number by, first, transducing them with a retrovirus encoding LigA, and then inactivating in these transductants endogenous Lig3 with CRISPR-Cas9. Interestingly, mtDNA depletion to an average level of one copy per cell proceeds faster in cells engineered to maintain mtDNA at low copy number. This makes a low-mtDNA copy number phenotype resulting from dependence on mitochondrial import of DNA ligase through presequence-independent pathway potentially useful for rapidly shifting mtDNA heteroplasmy through partial mtDNA depletion.

  6. Cumulative mtDNA damage and mutations contribute to the progressive loss of RGCs in a rat model of glaucoma.

    PubMed

    Wu, Ji-hong; Zhang, Sheng-hai; Nickerson, John M; Gao, Feng-juan; Sun, Zhongmou; Chen, Xin-ya; Zhang, Shu-Jie; Zhang, Rong; Gao, Feng; Chen, Jun-yi; Luo, Yi; Wang, Yan; Sun, Xing-huai

    2015-02-01

    Glaucoma is a chronic neurodegenerative disease characterized by the progressive loss of retinal ganglion cells (RGCs). Mitochondrial DNA (mtDNA) alterations have been documented as a key component of many neurodegenerative disorders. However, whether mtDNA alterations contribute to the progressive loss of RGCs and the mechanism whereby this phenomenon could occur are poorly understood. We investigated mtDNA alterations in RGCs using a rat model of chronic intraocular hypertension and explored the mechanisms underlying progressive RGC loss. We demonstrate that the mtDNA damage and mutations triggered by intraocular pressure (IOP) elevation are initiating, crucial events in a cascade leading to progressive RGC loss. Damage to and mutation of mtDNA, mitochondrial dysfunction, reduced levels of mtDNA repair/replication enzymes, and elevated reactive oxygen species form a positive feedback loop that produces irreversible mtDNA damage and mutation and contributes to progressive RGC loss, which occurs even after a return to normal IOP. Furthermore, we demonstrate that mtDNA damage and mutations increase the vulnerability of RGCs to elevated IOP and glutamate levels, which are among the most common glaucoma insults. This study suggests that therapeutic approaches that target mtDNA maintenance and repair and that promote energy production may prevent the progressive death of RGCs.

  7. Presequence-Independent Mitochondrial Import of DNA Ligase Facilitates Establishment of Cell Lines with Reduced mtDNA Copy Number

    PubMed Central

    Spadafora, Domenico; Kozhukhar, Natalia; Alexeyev, Mikhail F.

    2016-01-01

    Due to the essential role played by mitochondrial DNA (mtDNA) in cellular physiology and bioenergetics, methods for establishing cell lines with altered mtDNA content are of considerable interest. Here, we report evidence for the existence in mammalian cells of a novel, low- efficiency, presequence-independent pathway for mitochondrial protein import, which facilitates mitochondrial uptake of such proteins as Chlorella virus ligase (ChVlig) and Escherichia coli LigA. Mouse cells engineered to depend on this pathway for mitochondrial import of the LigA protein for mtDNA maintenance had severely (up to >90%) reduced mtDNA content. These observations were used to establish a method for the generation of mouse cell lines with reduced mtDNA copy number by, first, transducing them with a retrovirus encoding LigA, and then inactivating in these transductants endogenous Lig3 with CRISPR-Cas9. Interestingly, mtDNA depletion to an average level of one copy per cell proceeds faster in cells engineered to maintain mtDNA at low copy number. This makes a low-mtDNA copy number phenotype resulting from dependence on mitochondrial import of DNA ligase through presequence-independent pathway potentially useful for rapidly shifting mtDNA heteroplasmy through partial mtDNA depletion. PMID:27031233

  8. mtDNA and Y-chromosome polymorphisms in four Native American populations from southern Mexico

    SciTech Connect

    Torroni, A.; Chen, Yu.S.; Lott, M.T.; Wallace, D.C. ); Semino, O.; Santachiara-Beneceretti, A.S. ); Scott, C.R. ); Winter, M. )

    1994-02-01

    mtDNA sequence variation was examined in 60 Native Americans (Mixtecs from the Alta, Mixtecs from the Baja, Valley Zapotecs, and Highland Mixe) from southern Mexico by PCR amplification and high-resolution restriction endonuclease analysis. Four groups of mtDNA haplotypes (haplogroups A,B,C, and D) characterize Amerind populations. The comparison of their mtDNA variation with that observed in other populations from Mexico and Central America permits a clear distinction among the different Middle American tribes and raises questions about some of their linguistic affiliations. The males of these population samples were also analyzed for Y-chromosome RFLPs with the probes 49a, 49f, and 12f2. This analysis suggests that certain Y-chromosome haplotypes were brought from Asia during the colonization of the Americas, and a differential gene flow was introduced into Native American populations from European males and females. 31 refs., 4 figs., 5 tabs.

  9. In vivo levels of mitochondrial hydrogen peroxide increase with age in mtDNA mutator mice.

    PubMed

    Logan, Angela; Shabalina, Irina G; Prime, Tracy A; Rogatti, Sebastian; Kalinovich, Anastasia V; Hartley, Richard C; Budd, Ralph C; Cannon, Barbara; Murphy, Michael P

    2014-08-01

    In mtDNA mutator mice, mtDNA mutations accumulate leading to a rapidly aging phenotype. However, there is little evidence of oxidative damage to tissues, and when analyzed ex vivo, no change in production of the reactive oxygen species (ROS) superoxide and hydrogen peroxide by mitochondria has been reported, undermining the mitochondrial oxidative damage theory of aging. Paradoxically, interventions that decrease mitochondrial ROS levels in vivo delay onset of aging. To reconcile these findings, we used the mitochondria-targeted mass spectrometry probe MitoB to measure hydrogen peroxide within mitochondria of living mice. Mitochondrial hydrogen peroxide was the same in young mutator and control mice, but as the mutator mice aged, hydrogen peroxide increased. This suggests that the prolonged presence of mtDNA mutations in vivo increases hydrogen peroxide that contributes to an accelerated aging phenotype, perhaps through the activation of pro-apoptotic and pro-inflammatory redox signaling pathways.

  10. Variation in germ line mtDNA heteroplasmy is determined prenatally but modified during subsequent transmission

    PubMed Central

    Freyer, Christoph; Cree, Lynsey M.; Mourier, Arnaud; Stewart, James B.; Koolmeister, Camilla; Milenkovic, Dusanka; Wai, Timothy; Floros, Vasileios I.; Hagström, Erik; Chatzidaki, Emmanouella E.; Wiesner, Rudolph J.; Samuels, David C; Larsson, Nils-Göran; Chinnery, Patrick F.

    2012-01-01

    A genetic bottleneck explains the marked changes in mitochondrial DNA (mtDNA) heteroplasmy observed during the transmission of pathogenic mutations, but the precise timing remains controversial, and it is not clear whether selection plays a role. These issues are critically important for the genetic counseling of prospective mothers, and developing treatments aimed at disease prevention. By studying mice transmitting a heteroplasmic single base-pair deletion in the mitochondrial tRNAMet gene, we show that mammalian mtDNA heteroplasmy levels are principally determined prenatally within the developing female germ line. Although we saw no evidence of mtDNA selection prenatally, skewed heteroplasmy levels were observed in the offspring of the next generation, consistent with purifying selection. High percentage levels of the tRNAMet mutation were linked to a compensatory increase in overall mitochondrial RNAs, ameliorating the biochemical phenotype, and explaining why fecundity is not compromised. PMID:23042113

  11. The origin of Chinese domestic horses revealed with novel mtDNA variants.

    PubMed

    Yang, Yunzhou; Zhu, Qiyun; Liu, Shuqin; Zhao, Chunjiang; Wu, Changxin

    2017-01-01

    The origin of domestic horses in China was a controversial issue and several hypotheses including autochthonous domestication, introduction from other areas, and multiple-origins from both introduction and local wild horse introgression have been proposed, but none of them have been fully supported by DNA data. In the present study, mitochondrial DNA (mtDNA) sequences of 714 Chinese indigenous horses were analyzed. The results showed that Chinese domestic horses harbor some novel mtDNA haplogroups and suggested that local domestication events may have occurred, but they are not the dominant haplogroups and the geographical distributions of the novel mtDNA haplogroups were rather restricted. Conclusively, our results support the hypothesis that the domestic horses in China originated from both the introduced horses from outside of China and the local wild horses' introgression into the domestic populations. Results of genetic diversity analysis suggested a possibility that the introduced horses entered China through northern regions from the Eurasian steppe.

  12. mtDNA mutation C1494T, haplogroup A, and hearing loss in Chinese

    SciTech Connect

    Wang Chengye; Kong Qingpeng; Yao Yonggang . E-mail: ygyaozh@yahoo.com; Zhang Yaping

    2006-09-22

    Mutation C1494T in mitochondrial 12S rRNA gene was recently reported in two large Chinese families with aminoglycoside-induced and nonsyndromic hearing loss (AINHL) and was claimed to be pathogenic. This mutation, however, was first reported in a sample from central China in our previous study that was aimed to reconstruct East Asian mtDNA phylogeny. All these three mtDNAs formed a subclade defined by mutation C1494T in mtDNA haplogroup A. It thus seems that mutation C1494T is a haplogroup A-associated mutation and this matrilineal background may contribute a high risk for the penetrance of mutation C1494T in Chinese with AINHL. To test this hypothesis, we first genotyped mutation C1494T in 553 unrelated individuals from three regional Chinese populations and performed an extensive search for published complete or near-complete mtDNA data sets (>3000 mtDNAs), we then screened the C1494T mutation in 111 mtDNAs with haplogroup A status that were identified from 1823 subjects across China. The search for published mtDNA data sets revealed no other mtDNA besides the above-mentioned three carrying mutation C1494T. None of the 553 randomly selected individuals and the 111 haplogroup A mtDNAs was found to bear this mutation. Therefore, our results suggest that C1494T is a very rare event. The mtDNA haplogroup A background in general is unlikely to play an active role in the penetrance of mutation C1494T in AINHL.

  13. Chronic progressive ophthalmoplegia with large-scale mtDNA rearrangement: can we predict progression?

    PubMed

    Auré, Karine; Ogier de Baulny, Hélène; Laforêt, Pascal; Jardel, Claude; Eymard, Bruno; Lombès, Anne

    2007-06-01

    The prognosis of chronic progressive ophthalmoplegia with large-scale mitochondrial DNA (mtDNA) may strikingly vary from mild slowly progressive myopathy to severe multi-organ involvement. Evaluation of the disease course at the beginning of the disease is reputed impossible. To address the existence of predictive prognostic clues of these diseases, we classified 69 patients with chronic progressive ophthalmoplegia and large size mtDNA deletion into two groups according to the presence of manifestations from brain, inner ear or retina. These manifestations were present in 29 patients (CPEO/+N group) and absent in 40 patients (CPEO/-N group). We retrospectively established the clinical history of the patients and characterized their genetic alteration (amount of residual normal mtDNA molecules, site, size and percentage of the mtDNA deletion in 116 DNA samples from muscle, blood, urinary and buccal cells). In both clinical groups, the disease was progressive and heart conduction defects were frequent. We show that the CPEO/+N phenotype segregated with severe prognosis in term of rate of progression, multi-organs involvement and rate of survival. Age at onset appeared a predictive factor. The risk to develop a CPEO/+N phenotype was high when onset was before 9 years of age and low when onset was after 20 years of age. The presence and proportion of the mtDNA deletion in blood was also significantly associated with the CPEO/+N phenotype. This study is the first to establish the natural history of chronic ophthalmoplegia with mtDNA deletion in a large series of patients and to look for parameters potentially predictive of the patients' clinical course.

  14. DNA methyltransferase 1 mutations and mitochondrial pathology: is mtDNA methylated?

    PubMed Central

    Maresca, Alessandra; Zaffagnini, Mirko; Caporali, Leonardo; Carelli, Valerio; Zanna, Claudia

    2015-01-01

    Autosomal dominant cerebellar ataxia-deafness and narcolepsy (ADCA-DN) and Hereditary sensory neuropathy with dementia and hearing loss (HSN1E) are two rare, overlapping neurodegenerative syndromes that have been recently linked to allelic dominant pathogenic mutations in the DNMT1 gene, coding for DNA (cytosine-5)-methyltransferase 1 (DNMT1). DNMT1 is the enzyme responsible for maintaining the nuclear genome methylation patterns during the DNA replication and repair, thus regulating gene expression. The mutations responsible for ADCA-DN and HSN1E affect the replication foci targeting sequence domain, which regulates DNMT1 binding to chromatin. DNMT1 dysfunction is anticipated to lead to a global alteration of the DNA methylation pattern with predictable downstream consequences on gene expression. Interestingly, ADCA-DN and HSN1E phenotypes share some clinical features typical of mitochondrial diseases, such as optic atrophy, peripheral neuropathy, and deafness, and some biochemical evidence of mitochondrial dysfunction. The recent discovery of a mitochondrial isoform of DNMT1 and its proposed role in methylating mitochondrial DNA (mtDNA) suggests that DNMT1 mutations may directly affect mtDNA and mitochondrial physiology. On the basis of this latter finding the link between DNMT1 abnormal activity and mitochondrial dysfunction in ADCA-DN and HSN1E appears intuitive, however, mtDNA methylation remains highly debated. In the last years several groups demonstrated the presence of 5-methylcytosine in mtDNA by different approaches, but, on the other end, the opposite evidence that mtDNA is not methylated has also been published. Since over 1500 mitochondrial proteins are encoded by the nuclear genome, the altered methylation of these genes may well have a critical role in leading to the mitochondrial impairment observed in ADCA-DN and HSN1E. Thus, many open questions still remain unanswered, such as why mtDNA should be methylated, and how this process is regulated and

  15. Stochastic modelling, Bayesian inference, and new in vivo measurements elucidate the debated mtDNA bottleneck mechanism

    PubMed Central

    Johnston, Iain G; Burgstaller, Joerg P; Havlicek, Vitezslav; Kolbe, Thomas; Rülicke, Thomas; Brem, Gottfried; Poulton, Jo; Jones, Nick S

    2015-01-01

    Dangerous damage to mitochondrial DNA (mtDNA) can be ameliorated during mammalian development through a highly debated mechanism called the mtDNA bottleneck. Uncertainty surrounding this process limits our ability to address inherited mtDNA diseases. We produce a new, physically motivated, generalisable theoretical model for mtDNA populations during development, allowing the first statistical comparison of proposed bottleneck mechanisms. Using approximate Bayesian computation and mouse data, we find most statistical support for a combination of binomial partitioning of mtDNAs at cell divisions and random mtDNA turnover, meaning that the debated exact magnitude of mtDNA copy number depletion is flexible. New experimental measurements from a wild-derived mtDNA pairing in mice confirm the theoretical predictions of this model. We analytically solve a mathematical description of this mechanism, computing probabilities of mtDNA disease onset, efficacy of clinical sampling strategies, and effects of potential dynamic interventions, thus developing a quantitative and experimentally-supported stochastic theory of the bottleneck. DOI: http://dx.doi.org/10.7554/eLife.07464.001 PMID:26035426

  16. Hybridization and massive mtDNA unidirectional introgression between the closely related Neotropical toads Rhinella marina and R. schneideri inferred from mtDNA and nuclear markers

    PubMed Central

    2011-01-01

    Background The classical perspective that interspecific hybridization in animals is rare has been changing due to a growing list of empirical examples showing the occurrence of gene flow between closely related species. Using sequence data from cyt b mitochondrial gene and three intron nuclear genes (RPL9, c-myc, and RPL3) we investigated patterns of nucleotide polymorphism and divergence between two closely related toad species R. marina and R. schneideri. By comparing levels of differentiation at nuclear and mtDNA levels we were able to describe patterns of introgression and infer the history of hybridization between these species. Results All nuclear loci are essentially concordant in revealing two well differentiated groups of haplotypes, corresponding to the morphologically-defined species R. marina and R. schneideri. Mitochondrial DNA analysis also revealed two well-differentiated groups of haplotypes but, in stark contrast with the nuclear genealogies, all R. schneideri sequences are clustered with sequences of R. marina from the right Amazon bank (RAB), while R. marina sequences from the left Amazon bank (LAB) are monophyletic. An Isolation-with-Migration (IM) analysis using nuclear data showed that R. marina and R. schneideri diverged at ≈ 1.69 Myr (early Pleistocene), while R. marina populations from LAB and RAB diverged at ≈ 0.33 Myr (middle Pleistocene). This time of divergence is not consistent with the split between LAB and RAB populations obtained with mtDNA data (≈ 1.59 Myr), which is notably similar to the estimate obtained with nuclear genes between R. marina and R. schneideri. Coalescent simulations of mtDNA phylogeny under the speciation history inferred from nuclear genes rejected the hypothesis of incomplete lineage sorting to explain the conflicting signal between mtDNA and nuclear-based phylogenies. Conclusions The cytonuclear discordance seems to reflect the occurrence of interspecific hybridization between these two closely related

  17. mtDNA analysis of a prehistoric Oneota population: implications for the peopling of the New World.

    PubMed Central

    Stone, A C; Stoneking, M

    1998-01-01

    mtDNA was successfully extracted from 108 individuals from the Norris Farms Oneota, a prehistoric Native American population, to compare the mtDNA diversity from a pre-Columbian population with contemporary Native American and Asian mtDNA lineages and to examine hypotheses about the peopling of the New World. Haplogroup and hypervariable region I sequence data indicate that the lineages from haplogroups A, B, C, and D are the most common among Native Americans but that they were not the only lineages brought into the New World from Asia. The mtDNA evidence does not support the three-wave hypothesis of migration into the New World but rather suggests a single "wave" of people with considerable mtDNA diversity that exhibits a signature of expansion 23,000-37,000 years ago. PMID:9545408

  18. Cattle ancestry in bison: explanations for higher mtDNA than autosomal ancestry.

    PubMed

    Hedrick, Philip W

    2010-08-01

    Understanding and documenting the process of hybridization and introgression between related species is a major focus of recent evolutionary research using molecular techniques. Many North American bison herds have cattle ancestry introduced by crossbreeding over a century ago. Molecular estimates of this ancestry have shown much higher levels for cattle mtDNA than for autosomal cattle genes. A large part of this difference appears to be the result of partial reproductive isolation between the two species where only bison bull x domestic cow crosses are successful, and all the surviving progeny are females. In addition, selection against autosomal cattle genes in bison may have contributed to differential levels of cattle ancestry. The impact of selection against cattle mtDNA and gene flow of bison mtDNA are examined to explain particular combinations of mtDNA and autosomal cattle ancestry. A bottleneck, after the level of cattle ancestry in bison was reduced to a low level, is consistent with the high variance over autosomal loci observed for cattle ancestry, and differential selection among cattle loci in bison does not need to be invoked. Further examination of the cattle genome in bison may shed light on whether these markers, or their associated regions, are indeed neutral.

  19. Transcript Mapping and Genome Annotation of Ascidian mtDNA Using EST Data

    PubMed Central

    Gissi, Carmela; Pesole, Graziano

    2003-01-01

    Mitochondrial transcripts of two ascidian species were reconstructed through sequence assembly of publicly available ESTs resembling mitochondrial DNA sequences (mt-ESTs). This strategy allowed us to analyze processing and mapping of the mitochondrial transcripts and to investigate the gene organization of a previously uncharacterized mitochondrial genome (mtDNA). This new strategy would greatly facilitate the sequencing and annotation of mtDNAs. In Ciona intestinalis, the assembled mt-ESTs covered 22 mitochondrial genes (∼12,000 bp) and provided the partial sequence of the mtDNA and the prediction of its gene organization. Such sequences were confirmed by amplification and sequencing of the entire Ciona mtDNA. For Halocynthia roretzi, for which the mtDNA sequence was already available, the inferred mt transcripts allowed better definition of gene boundaries (16S rRNA, ND1, ATP6, and tRNA-Ser genes) and the identification of a new gene (an additional Phe-tRNA). In both species, polycistronic and immature transcripts, creation of stop codons by polyadenylation, tRNA signal processing, and rRNA transcript termination signals were identified, thus suggesting that the main features of mitochondrial transcripts are conserved in Chordata. PMID:12915488

  20. Disuniting uniformity: a pied cladistic canvas of mtDNA haplogroup H in Eurasia.

    PubMed

    Loogväli, Eva-Liis; Roostalu, Urmas; Malyarchuk, Boris A; Derenko, Miroslava V; Kivisild, Toomas; Metspalu, Ene; Tambets, Kristiina; Reidla, Maere; Tolk, Helle-Viivi; Parik, Jüri; Pennarun, Erwan; Laos, Sirle; Lunkina, Arina; Golubenko, Maria; Barac, Lovorka; Pericic, Marijana; Balanovsky, Oleg P; Gusar, Vladislava; Khusnutdinova, Elsa K; Stepanov, Vadim; Puzyrev, Valery; Rudan, Pavao; Balanovska, Elena V; Grechanina, Elena; Richard, Christelle; Moisan, Jean-Paul; Chaventré, André; Anagnou, Nicholas P; Pappa, Kalliopi I; Michalodimitrakis, Emmanuel N; Claustres, Mireille; Gölge, Mukaddes; Mikerezi, Ilia; Usanga, Esien; Villems, Richard

    2004-11-01

    It has been often stated that the overall pattern of human maternal lineages in Europe is largely uniform. Yet this uniformity may also result from an insufficient depth and width of the phylogenetic analysis, in particular of the predominant western Eurasian haplogroup (Hg) H that comprises nearly a half of the European mitochondrial DNA (mtDNA) pool. Making use of the coding sequence information from 267 mtDNA Hg H sequences, we have analyzed 830 mtDNA genomes, from 11 European, Near and Middle Eastern, Central Asian, and Altaian populations. In addition to the seven previously specified subhaplogroups, we define fifteen novel subclades of Hg H present in the extant human populations of western Eurasia. The refinement of the phylogenetic resolution has allowed us to resolve a large number of homoplasies in phylogenetic trees of Hg H based on the first hypervariable segment (HVS-I) of mtDNA. As many as 50 out of 125 polymorphic positions in HVS-I were found to be mutated in more than one subcluster of Hg H. The phylogeographic analysis revealed that sub-Hgs H1*, H1b, H1f, H2a, H3, H6a, H6b, and H8 demonstrate distinct phylogeographic patterns. The monophyletic subhaplogroups of Hg H provide means for further progress in the understanding of the (pre)historic movements of women in Eurasia and for the understanding of the present-day genetic diversity of western Eurasians in general.

  1. HAPLOFIND: a new method for high-throughput mtDNA haplogroup assignment.

    PubMed

    Vianello, Dario; Sevini, Federica; Castellani, Gastone; Lomartire, Laura; Capri, Miriam; Franceschi, Claudio

    2013-09-01

    Deep sequencing technologies are completely revolutionizing the approach to DNA analysis. Mitochondrial DNA (mtDNA) studies entered in the "postgenomic era": the burst in sequenced samples observed in nuclear genomics is expected also in mitochondria, a trend that can already be detected checking complete mtDNA sequences database submission rate. Tools for the analysis of these data are available, but they fail in throughput or in easiness of use. We present here a new pipeline based on previous algorithms, inherited from the "nuclear genomic toolbox," combined with a newly developed algorithm capable of efficiently and easily classify new mtDNA sequences according to PhyloTree nomenclature. Detected mutations are also annotated using data collected from publicly available databases. Thanks to the analysis of all freely available sequences with known haplogroup obtained from GenBank, we were able to produce a PhyloTree-based weighted tree, taking into account each haplogroup pattern conservation. The combination of a highly efficient aligner, coupled with our algorithm and massive usage of asynchronous parallel processing, allowed us to build a high-throughput pipeline for the analysis of mtDNA sequences that can be quickly updated to follow the ever-changing nomenclature. HaploFind is freely accessible at the following Web address: https://haplofind.unibo.it.

  2. Insertion of a self-splicing intron into the mtDNA of atriploblastic animal

    SciTech Connect

    Valles, Y.; Halanych, K.; Boore, J.L.

    2006-04-14

    Nephtys longosetosa is a carnivorous polychaete worm that lives in the intertidal and subtidal zones with worldwide distribution (pleijel&rouse2001). Its mitochondrial genome has the characteristics typical of most metazoans: 37 genes; circular molecule; almost no intergenic sequence; and no significant gene rearrangements when compared to other annelid mtDNAs (booremoritz19981995). Ubiquitous features as small intergenic regions and lack of introns suggested that metazoan mtDNAs are under strong selective pressures to reduce their genome size allowing for faster replication requirements (booremoritz19981995Lynch2005). Yet, in 1996 two type I introns were found in the mtDNA of the basal metazoan Metridium senile (FigureX). Breaking a long-standing rule (absence of introns in metazoan mtDNA), this finding was later supported by the further presence of group I introns in other cnidarians. Interestingly, only the class Anthozoa within cnidarians seems to harbor such introns. Although several hundreds of triploblastic metazoan mtDNAs have been sequenced, this study is the first evidence of mitochondrial introns in triploblastic metazoans. The cox1 gene of N. longosetosa has an intron of almost 2 kbs in length. This finding represents as well the first instance of a group II intron (anthozoans harbor group I introns) in all metazoan lineages. Opposite trends are observed within plants, fungi and protist mtDNAs, where introns (both group I and II) and other non-coding sequences are widespread. Plant, fungal and protist mtDNA structure and organization differ enormously from that of metazoan mtDNA. Both, plant and fungal mtDNA are dynamic molecules that undergo high rates of recombination, contain long intergenic spacer regions and harbor both group I and group II introns. However, as metazoans they have a conserved gene content. Protists, on the other hand have a striking variation of gene content and introns that account for the genome size variation. In contrast to

  3. Range-wide mtDNA phylogeography yields insights into the origins of Asian elephants

    PubMed Central

    Vidya, T.N.C.; Sukumar, Raman; Melnick, Don J.

    2008-01-01

    Recent phylogeographic studies of the endangered Asian elephant (Elephas maximus) reveal two highly divergent mitochondrial DNA (mtDNA) lineages, an elucidation of which is central to understanding the species's evolution. Previous explanations for the divergent clades include introgression of mtDNA haplotypes between ancestral species, allopatric divergence of the clades between Sri Lanka or the Sunda region and the mainland, historical trade of elephants, and retention of divergent lineages due to large population sizes. However, these studies lacked data from India and Myanmar, which host approximately 70 per cent of all extant Asian elephants. In this paper, we analyse mtDNA sequence data from 534 Asian elephants across the species's range to explain the current distribution of the two divergent clades. Based on phylogenetic reconstructions, estimates of times of origin of clades, probable ancestral areas of origin inferred from dispersal–vicariance analyses and the available fossil record, we believe both clades originated from Elephas hysudricus. This probably occurred allopatrically in different glacial refugia, the α clade in the Myanmar region and the β clade possibly in southern India–Sri Lanka, 1.6–2.1 Myr ago. Results from nested clade and dispersal–vicariance analyses indicate a subsequent isolation and independent diversification of the β clade in both Sri Lanka and the Sunda region, followed by northward expansion of the clade. We also find more recent population expansions in both clades based on mismatch distributions. We therefore suggest a contraction–expansion scenario during severe climatic oscillations of the Quaternary, with range expansions from different refugia during warmer interglacials leading to the varying geographical overlaps of the two mtDNA clades. We also demonstrate that trade in Asian elephants has not substantially altered the species's mtDNA population genetic structure. PMID:19019786

  4. Range-wide mtDNA phylogeography yields insights into the origins of Asian elephants.

    PubMed

    Vidya, T N C; Sukumar, Raman; Melnick, Don J

    2009-03-07

    Recent phylogeographic studies of the endangered Asian elephant (Elephas maximus) reveal two highly divergent mitochondrial DNA (mtDNA) lineages, an elucidation of which is central to understanding the species's evolution. Previous explanations for the divergent clades include introgression of mtDNA haplotypes between ancestral species, allopatric divergence of the clades between Sri Lanka or the Sunda region and the mainland, historical trade of elephants, and retention of divergent lineages due to large population sizes. However, these studies lacked data from India and Myanmar, which host approximately 70 per cent of all extant Asian elephants. In this paper, we analyse mtDNA sequence data from 534 Asian elephants across the species's range to explain the current distribution of the two divergent clades. Based on phylogenetic reconstructions, estimates of times of origin of clades, probable ancestral areas of origin inferred from dispersal-vicariance analyses and the available fossil record, we believe both clades originated from Elephas hysudricus. This probably occurred allopatrically in different glacial refugia, the alpha clade in the Myanmar region and the beta clade possibly in southern India-Sri Lanka, 1.6-2.1Myr ago. Results from nested clade and dispersal-vicariance analyses indicate a subsequent isolation and independent diversification of the beta clade in both Sri Lanka and the Sunda region, followed by northward expansion of the clade. We also find more recent population expansions in both clades based on mismatch distributions. We therefore suggest a contraction-expansion scenario during severe climatic oscillations of the Quaternary, with range expansions from different refugia during warmer interglacials leading to the varying geographical overlaps of the two mtDNA clades. We also demonstrate that trade in Asian elephants has not substantially altered the species's mtDNA population genetic structure.

  5. RNASEH1 Mutations Impair mtDNA Replication and Cause Adult-Onset Mitochondrial Encephalomyopathy

    PubMed Central

    Reyes, Aurelio; Melchionda, Laura; Nasca, Alessia; Carrara, Franco; Lamantea, Eleonora; Zanolini, Alice; Lamperti, Costanza; Fang, Mingyan; Zhang, Jianguo; Ronchi, Dario; Bonato, Sara; Fagiolari, Gigliola; Moggio, Maurizio; Ghezzi, Daniele; Zeviani, Massimo

    2015-01-01

    Chronic progressive external ophthalmoplegia (CPEO) is common in mitochondrial disorders and is frequently associated with multiple mtDNA deletions. The onset is typically in adulthood, and affected subjects can also present with general muscle weakness. The underlying genetic defects comprise autosomal-dominant or recessive mutations in several nuclear genes, most of which play a role in mtDNA replication. Next-generation sequencing led to the identification of compound-heterozygous RNASEH1 mutations in two singleton subjects and a homozygous mutation in four siblings. RNASEH1, encoding ribonuclease H1 (RNase H1), is an endonuclease that is present in both the nucleus and mitochondria and digests the RNA component of RNA-DNA hybrids. Unlike mitochondria, the nucleus harbors a second ribonuclease (RNase H2). All affected individuals first presented with CPEO and exercise intolerance in their twenties, and these were followed by muscle weakness, dysphagia, and spino-cerebellar signs with impaired gait coordination, dysmetria, and dysarthria. Ragged-red and cytochrome c oxidase (COX)-negative fibers, together with impaired activity of various mitochondrial respiratory chain complexes, were observed in muscle biopsies of affected subjects. Western blot analysis showed the virtual absence of RNase H1 in total lysate from mutant fibroblasts. By an in vitro assay, we demonstrated that altered RNase H1 has a reduced capability to remove the RNA from RNA-DNA hybrids, confirming their pathogenic role. Given that an increasing amount of evidence indicates the presence of RNA primers during mtDNA replication, this result might also explain the accumulation of mtDNA deletions and underscores the importance of RNase H1 for mtDNA maintenance. PMID:26094573

  6. Second generation sequencing allows for mtDNA mixture deconvolution and high resolution detection of heteroplasmy

    PubMed Central

    Holland, Mitchell M.; McQuillan, Megan R.; O’Hanlon, Katherine A.

    2011-01-01

    Aim To use parallel array pyrosequencing to deconvolute mixtures of mitochondrial DNA (mtDNA) sequence and provide high resolution analysis of mtDNA heteroplasmy. Methods The hypervariable segment 1 (HV1) of the mtDNA control region was analyzed from 30 individuals using the 454 GS Junior instrument. Mock mixtures were used to evaluate the system’s ability to deconvolute mixtures and to reliably detect heteroplasmy, including heteroplasmic differences between 5 family members of the same maternal lineage. Amplicon sequencing was performed on polymerase chain reaction (PCR) products generated with primers that included multiplex identifiers (MID) and adaptors for pyrosequencing. Data analysis was performed using NextGENe® software. The analysis of an autosomal short tandem repeat (STR) locus (D18S51) and a Y-STR locus (DYS389 I/II) was performed simultaneously with a portion of HV1 to illustrate that multiplexing can encompass different markers of forensic interest. Results Mixtures, including heteroplasmic variants, can be detected routinely down to a component ratio of 1:250 (20 minor variant copies with a coverage rate of 5000 sequences) and can be readily detected down to 1:1000 (0.1%) with expanded coverage. Amplicon sequences from D18S51, DYS389 I/II, and the second half of HV1 were successfully partitioned and analyzed. Conclusions The ability to routinely deconvolute mtDNA mixtures down to a level of 1:250 allows for high resolution analysis of mtDNA heteroplasmy, and for differentiation of individuals from the same maternal lineage. The pyrosequencing approach results in poor resolution of homopolymeric sequences, and PCR/sequencing artifacts require a filtering mechanism similar to that for STR stutter and spectral bleed through. In addition, chimeric sequences from jumping PCR must be addressed to make the method operational. PMID:21674826

  7. Evolutionary neutrality of mtDNA introgression: evidence from complete mitogenome analysis in roe deer.

    PubMed

    Matosiuk, M; Sheremetyeva, I N; Sheremetyev, I S; Saveljev, A P; Borkowska, A

    2014-11-01

    Introgressive hybridization offers a unique platform for studying the molecular basis of natural selection acting on mitogenomes. Most of the mtDNA protein-coding genes are extremely conserved; however, some of the observed variations have potentially adaptive significance. Here, we evaluated whether the evolution of mtDNA in closely related roe deer species affected by widespread mtDNA introgression is neutral or adaptive. We characterized and compared 16 complete mitogenomes of European (Capreolus capreolus) and Siberian (C. pygargus) roe deer, including four of Siberian origin introgressed into European species. The average sequence divergence of species-specific lineages was estimated at 2.8% and varied across gene classes. Only 21 of 315 fixed differences identified in protein-coding genes represented nonsynonymous changes. Only three of them were determined to have arisen in the C. pygargus lineage since the time to the most recent common ancestor (TMRCA) of both Capreolus species, reflecting a decelerated evolutionary ratio. The almost four-fold higher dN /dS ratio described for the European roe deer lineage is constrained by overall purifying selection, especially pronounced in the ND4 and ND5 genes. We suggest that the highly divergent C. capreolus lineage could have maintained a capability for genomic incorporation of the well-preserved and almost ancestral type of mtDNA present in C. pygargus. Our analyses did not indicate any signs of positive selection for Siberian roe deer mtDNA, suggesting that the present widespread introgression is evolutionarily neutral.

  8. Integration

    ERIC Educational Resources Information Center

    Kalyn, Brenda

    2006-01-01

    Integrated learning is an exciting adventure for both teachers and students. It is not uncommon to observe the integration of academic subjects such as math, science, and language arts. However, educators need to recognize that movement experiences in physical education also can be linked to academic curricula and, may even lead the…

  9. Integrity of the yeast mitochondrial genome, but not its distribution and inheritance, relies on mitochondrial fission and fusion.

    PubMed

    Osman, Christof; Noriega, Thomas R; Okreglak, Voytek; Fung, Jennifer C; Walter, Peter

    2015-03-03

    Mitochondrial DNA (mtDNA) is essential for mitochondrial and cellular function. In Saccharomyces cerevisiae, mtDNA is organized in nucleoprotein structures termed nucleoids, which are distributed throughout the mitochondrial network and are faithfully inherited during the cell cycle. How the cell distributes and inherits mtDNA is incompletely understood although an involvement of mitochondrial fission and fusion has been suggested. We developed a LacO-LacI system to noninvasively image mtDNA dynamics in living cells. Using this system, we found that nucleoids are nonrandomly spaced within the mitochondrial network and observed the spatiotemporal events involved in mtDNA inheritance. Surprisingly, cells deficient in mitochondrial fusion and fission distributed and inherited mtDNA normally, pointing to alternative pathways involved in these processes. We identified such a mechanism, where we observed fission-independent, but F-actin-dependent, tip generation that was linked to the positioning of mtDNA to the newly generated tip. Although mitochondrial fusion and fission were dispensable for mtDNA distribution and inheritance, we show through a combination of genetics and next-generation sequencing that their absence leads to an accumulation of mitochondrial genomes harboring deleterious structural variations that cluster at the origins of mtDNA replication, thus revealing crucial roles for mitochondrial fusion and fission in maintaining the integrity of the mitochondrial genome.

  10. The Enigmatic Origin of Bovine mtDNA Haplogroup R: Sporadic Interbreeding or an Independent Event of Bos primigenius Domestication in Italy?

    PubMed Central

    Bonfiglio, Silvia; Achilli, Alessandro; Olivieri, Anna; Negrini, Riccardo; Colli, Licia; Liotta, Luigi; Ajmone-Marsan, Paolo; Torroni, Antonio; Ferretti, Luca

    2010-01-01

    Background When domestic taurine cattle diffused from the Fertile Crescent, local wild aurochsen (Bos primigenius) were still numerous. Moreover, aurochsen and introduced cattle often coexisted for millennia, thus providing potential conditions not only for spontaneous interbreeding, but also for pastoralists to create secondary domestication centers involving local aurochs populations. Recent mitochondrial genomes analyses revealed that not all modern taurine mtDNAs belong to the shallow macro-haplogroup T of Near Eastern origin, as demonstrated by the detection of three branches (P, Q and R) radiating prior to the T node in the bovine phylogeny. These uncommon haplogroups represent excellent tools to evaluate if sporadic interbreeding or even additional events of cattle domestication occurred. Methodology The survey of the mitochondrial DNA (mtDNA) control-region variation of 1,747 bovine samples (1,128 new and 619 from previous studies) belonging to 37 European breeds allowed the identification of 16 novel non-T mtDNAs, which after complete genome sequencing were confirmed as members of haplogroups Q and R. These mtDNAs were then integrated in a phylogenetic tree encompassing all available P, Q and R complete mtDNA sequences. Conclusions Phylogenetic analyses of 28 mitochondrial genomes belonging to haplogroups P (N = 2), Q (N = 16) and R (N = 10) together with an extensive survey of all previously published mtDNA datasets revealed major similarities between haplogroups Q and T. Therefore, Q most likely represents an additional minor lineage domesticated in the Near East together with the founders of the T subhaplogroups. Whereas, haplogroup R is found, at least for the moment, only in Italy and nowhere else, either in modern or ancient samples, thus supporting an origin from European aurochsen. Haplogroup R could have been acquired through sporadic interbreeding of wild and domestic animals, but our data do not rule out the possibility of a local

  11. MtDNA meta-analysis reveals both phenotype specificity and allele heterogeneity: a model for differential association

    PubMed Central

    Marom, Shani; Friger, Michael; Mishmar, Dan

    2017-01-01

    Human mtDNA genetic variants have traditionally been considered markers for ancient population migrations. However, during the past three decades, these variants have been associated with altered susceptibility to various phenotypes, thus supporting their importance for human health. Nevertheless, mtDNA disease association has frequently been supported only in certain populations, due either to population stratification or differential epistatic compensations among populations. To partially overcome these obstacles, we performed meta-analysis of the multiple mtDNA association studies conducted until 2016, encompassing 53,975 patients and 63,323 controls. Our findings support the association of mtDNA haplogroups and recurrent variants with specific phenotypes such as Parkinson’s disease, type 2 diabetes, longevity, and breast cancer. Strikingly, our assessment of mtDNA variants’ involvement with multiple phenotypes revealed significant impact for Caucasian haplogroups H, J, and K. Therefore, ancient mtDNA variants could be divided into those that affect specific phenotypes, versus others with a general impact on phenotype combinations. We suggest that the mtDNA could serve as a model for phenotype specificity versus allele heterogeneity. PMID:28230165

  12. Seventeen New Complete mtDNA Sequences Reveal Extensive Mitochondrial Genome Evolution within the Demospongiae

    PubMed Central

    Wang, Xiujuan; Lavrov, Dennis V.

    2008-01-01

    Two major transitions in animal evolution–the origins of multicellularity and bilaterality–correlate with major changes in mitochondrial DNA (mtDNA) organization. Demosponges, the largest class in the phylum Porifera, underwent only the first of these transitions and their mitochondrial genomes display a peculiar combination of ancestral and animal-specific features. To get an insight into the evolution of mitochondrial genomes within the Demospongiae, we determined 17 new mtDNA sequences from this group and analyzing them with five previously published sequences. Our analysis revealed that all demosponge mtDNAs are 16- to 25-kbp circular molecules, containing 13–15 protein genes, 2 rRNA genes, and 2–27 tRNA genes. All but four pairs of sampled genomes had unique gene orders, with the number of shared gene boundaries ranging from 1 to 41. Although most demosponge species displayed low rates of mitochondrial sequence evolution, a significant acceleration in evolutionary rates occurred in the G1 group (orders Dendroceratida, Dictyoceratida, and Verticillitida). Large variation in mtDNA organization was also observed within the G0 group (order Homosclerophorida) including gene rearrangements, loss of tRNA genes, and the presence of two introns in Plakortis angulospiculatus. While introns are rare in modern-day demosponge mtDNA, we inferred that at least one intron was present in cox1 of the common ancestor of all demosponges. Our study uncovered an extensive mitochondrial genomic diversity within the Demospongiae. Although all sampled mitochondrial genomes retained some ancestral features, including a minimally modified genetic code, conserved structures of tRNA genes, and presence of multiple non-coding regions, they vary considerably in their size, gene content, gene order, and the rates of sequence evolution. Some of the changes in demosponge mtDNA, such as the loss of tRNA genes and the appearance of hairpin-containing repetitive elements, occurred in

  13. A call for mtDNA data quality control in forensic science.

    PubMed

    Yao, Yong-Gang; Bravi, Claudio M; Bandelt, Hans-Jürgen

    2004-04-20

    There is increasing evidence that many of the mitochondrial DNA (mtDNA) databases published in the fields of forensic science and molecular anthropology are flawed. An a posteriori phylogenetic analysis of the sequences could help to eliminate most of the errors and thus greatly improve data quality. However, previously published caveats and recommendations along these lines were not yet picked up by all researchers. Here we call for stringent quality control of mtDNA data by haplogroup-directed database comparisons. We take some problematic databases of East Asian mtDNAs, published in the Journal of Forensic Sciences and Forensic Science International, as examples to demonstrate the process of pinpointing obvious errors. Our results show that data sets are not only notoriously plagued by base shifts and artificial recombination but also by lab-specific phantom mutations, especially in the second hypervariable region (HVR-II).

  14. Mitochondrial DNA in Tumor Initiation, Progression, and Metastasis: Role of Horizontal mtDNA Transfer.

    PubMed

    Berridge, Michael V; Dong, Lanfeng; Neuzil, Jiri

    2015-08-15

    Mitochondrial DNA (mtDNA), encoding 13 out of more than 1,000 proteins of the mitochondrial proteome, is of paramount importance for the bioenergetic machinery of oxidative phosphorylation that is required for tumor initiation, propagation, and metastasis. In stark contrast to the widely held view that mitochondria and mtDNA are retained and propagated within somatic cells of higher organisms, recent in vitro and in vivo evidence demonstrates that mitochondria move between mammalian cells. This is particularly evident in cancer where defective mitochondrial respiration can be restored and tumor-forming ability regained by mitochondrial acquisition. This paradigm shift in cancer cell biology and mitochondrial genetics, concerning mitochondrial movement between cells to meet bioenergetic needs, not only adds another layer of plasticity to the armory of cancer cells to correct damaged mitochondria, but also points to potentially new therapeutic approaches.

  15. Non-randomized mtDNA damage after ionizing radiation via charge transport

    NASA Astrophysics Data System (ADS)

    Zhou, Xin; Liu, Xinguo; Zhang, Xin; Zhou, Rong; He, Yang; Li, Qiang; Wang, Zhenhua; Zhang, Hong

    2012-10-01

    Although it is well known that there are mutation hot spots in mtDNA, whether there are damage hot spots remain elusive. In this study, the regional DNA damage of mitochondrial genome after ionizing radiation was determined by real-time quantitative PCR. The mtDNA damage level was found to be dose-dependent and regional unequal. The control region was the most susceptible region to oxidative damage. GGG, as an typical hole trap during charge transport, was found to be disproportionally enriched in the control region. A total of 107 vertebrate mitochondrial genomes were then analyzed to testify whether the GGG enrichment in control region was evolutionary conserved. Surprisingly, the triple G enrichment can be observed in most of the homeothermal animals, while the majority of heterothermic animals showed no triple G enrichment. These results indicated that the triple G enrichment in control region was related to the mitochondrial metabolism during evolution.

  16. Two distinct mtDNA lineages among captive African penguins in Japan.

    PubMed

    Murata, Michiko; Murakami, Masaru

    2014-04-01

    The African penguin (Spheniscus demersus) is one of the world's most endangered seabirds. In Japan, although the number of African penguins in captivity continues to increase, genetic data have not been collected for either wild or captive populations. To reveal genetic diversity and characterization in captive African penguins, we analyzed the nucleotide sequences of mitochondrial DNA (mtDNA) from a sample of 236 African penguins. Analysis of 433 bp of the control region and 1,140 bp of cytochrome b sequences revealed the existence of two mtDNA clades. Control region haplotypes were much more divergent (d=3.39%) between the two clades than within each clade. The divergence of these clades may reflect differences at the subspecies or geographical population level in African penguins. These findings suggest that at least two distinct maternal lineages exist in the wild populations of the African penguin.

  17. Mitochondrial inheritance in budding yeasts: towards an integrated understanding.

    PubMed

    Solieri, Lisa

    2010-11-01

    Recent advances in yeast mitogenomics have significantly contributed to our understanding of the diversity of organization, structure and topology in the mitochondrial genome of budding yeasts. In parallel, new insights on mitochondrial DNA (mtDNA) inheritance in the model organism Saccharomyces cerevisiae highlighted an integrated scenario where recombination, replication and segregation of mtDNA are intricately linked to mitochondrial nucleoid (mt-nucleoid) structure and organelle sorting. In addition to this, recent discoveries of bifunctional roles of some mitochondrial proteins have interesting implications on mito-nuclear genome interactions and the relationship between mtDNA inheritance, yeast fitness and speciation. This review summarizes the current knowledge on yeast mitogenomics, mtDNA inheritance with regard to mt-nucleoid structure and organelle dynamics, and mito-nuclear genome interactions.

  18. Do mtDNA Mutations Participate in the Pathogenesis of Sporadic Parkinson’s Disease?

    PubMed Central

    Kirches, E.

    2009-01-01

    The pathogenesis of sporadic Parkinson’s disease (PD) remains enigmatic. Mitochondrial complex-I defects are known to occur in the substantia nigra (SN) of PD patients and are also debated in some extracerebral tissues. Early sequencing efforts of the mitochondrial DNA (mtDNA) did not reveal specific mutations, but a long lasting discussion was devoted to the issue of randomly distributed low level point mutations, caused by oxidative stress. However, a potential functional impact remained a matter of speculation, since heteroplasmy (mutational load) at any base position analyzed, remained far below the relevant functional threshold. A clearly age-dependent increase of the ‘common mtDNA deletion’ had been demonstrated in most brain regions by several authors since 1992. However, heteroplasmy did hardly exceed 1% of total mtDNA. It became necessary to exploit PCR techniques, which were able to detect any deletion in a few microdissected dopaminergic neurons of the SN. In 2006, two groups published biochemically relevant loads of somatic mtDNA deletions in these neurons. They seem to accumulate to relevant levels in the SN dopaminergic neurons of aged individuals in general, but faster in those developing PD. It is reasonable to assume that this accumulation causes mitochondrial dysfunction of the SN, although it cannot be taken as a final proof for an early pathogenetic role of this dysfunction. Recent studies demonstrate a distribution of deletion breakpoints, which does not differ between PD, aging and classical mitochondrial disorders, suggesting a common, but yet unknown mechanism. PMID:20514220

  19. Bridging near and remote Oceania: mtDNA and NRY variation in the Solomon Islands.

    PubMed

    Delfin, Frederick; Myles, Sean; Choi, Ying; Hughes, David; Illek, Robert; van Oven, Mannis; Pakendorf, Brigitte; Kayser, Manfred; Stoneking, Mark

    2012-02-01

    Although genetic studies have contributed greatly to our understanding of the colonization of Near and Remote Oceania, important gaps still exist. One such gap is the Solomon Islands, which extend between Bougainville and Vanuatu, thereby bridging Near and Remote Oceania, and include both Austronesian-speaking and Papuan-speaking groups. Here, we describe patterns of mitochondrial DNA (mtDNA) and nonrecombining Y chromosome (NRY) variation in over 700 individuals from 18 populations in the Solomons, including 11 Austronesian-speaking groups, 3 Papuan-speaking groups, and 4 Polynesian Outliers (descended via back migration from Polynesia). We find evidence for ancient (pre-Lapita) colonization of the Solomons in old NRY paragroups as well as from M2-M353, which probably arose in the Solomons ∼9,200 years ago and is the most frequent NRY haplogroup there. There are no consistent genetic differences between Austronesian-speaking and Papuan-speaking groups, suggesting extensive genetic contact between them. Santa Cruz, which is located in Remote Oceania, shows unusually low frequencies of mtDNA and NRY haplogroups of recent Asian ancestry. This is in apparent contradiction with expectations based on archaeological and linguistic evidence for an early (∼3,200 years ago), direct colonization of Santa Cruz by Lapita people from the Bismarck Archipelago, via a migration that "leapfrogged" over the rest of the Solomons. Polynesian Outliers show dramatic island-specific founder events involving various NRY haplogroups. We also find that NRY, but not mtDNA, genetic distance is correlated with the geographic distance between Solomons groups and that historically attested spheres of cultural interaction are associated with the recent genetic structure of Solomons groups, as revealed by mtDNA HV1 sequence and Y-STR haplotype diversity. Our results fill an important lacuna in human genetic studies of Oceania and aid in understanding the colonization and genetic history of

  20. Complete mtDNA genomes of Anopheles darlingi and an approach to anopheline divergence time

    PubMed Central

    2010-01-01

    Background The complete sequences of the mitochondrial genomes (mtDNA) of members of the northern and southern genotypes of Anopheles (Nyssorhynchus) darlingi were used for comparative studies to estimate the time to the most recent common ancestor for modern anophelines, to evaluate differentiation within this taxon, and to seek evidence of incipient speciation. Methods The mtDNAs were sequenced from mosquitoes from Belize and Brazil and comparative analyses of structure and base composition, among others, were performed. A maximum likelihood approach linked with phylogenetic information was employed to detect evidence of selection and a Bayesian approach was used to date the split between the subgenus Nyssorhynchus and other Anopheles subgenera. Results The comparison of mtDNA sequences within the Anopheles darlingi taxon does not provide sufficient resolution to establish different units of speciation within the species. In addition, no evidence of positive selection in any protein-coding gene of the mtDNA was detected, and purifying selection likely is the basis for this lack of diversity. Bayesian analysis supports the conclusion that the most recent ancestor of Nyssorhynchus and Anopheles+Cellia was extant ~94 million years ago. Conclusion Analyses of mtDNA genomes of Anopheles darlingi do not provide support for speciation in the taxon. The dates estimated for divergence among the anopheline groups tested is in agreement with the geological split of western Gondwana (95 mya), and provides additional support for explaining the absence of Cellia in the New World, and Nyssorhynchus in the Afro-Eurasian continents. PMID:20470395

  1. Pedigree analysis in Leber hereditary optic neuropathy families with a pathogenic mtDNA mutation.

    PubMed Central

    Harding, A E; Sweeney, M G; Govan, G G; Riordan-Eva, P

    1995-01-01

    Eighty-nine index patients from 85 families were defined as having Leber hereditary optic neuropathy (LHON) by the presence of one of the mtDNA mutations at positions 11778 (66 families), 3460 (8 families), or 14484 (11 families). There were 62 secondary cases. Overall, 64% of index cases had a history of similarly affected relatives. The ratios of affected males to affected females were 3.7:1 (11778), 4.3:1 (3460), and 7.7:1 (14484). The 95th centile for age at onset of symptoms was close to 50 years in index, secondary, male, and female patients. There were no differences in the distributions of age at onset between different mutation groups, between index and secondary cases, or between males and females, apart from this being slightly later in all female patients than in male 11778 patients. There was no significant correlation between age at onset in index cases and that in their affected siblings or cousins. Heteroplasmy (< 96% mutant mtDNA) was detected in 4% of affected subjects (67%-90% mutant mtDNA) and in 13.6% of 140 unaffected relatives (< 5%-90% mutant mtDNA). Analysis of all pedigrees, excluding sibships < 50 years of age and index cases, indicated recurrence risks of 30%, 8%, 46%, 10%, 31%, and 6%, respectively, to the brothers, sisters, nephews, nieces, and male and female matrilineal first cousins of index cases. Affected females were more likely to have affected children, particularly daughters, than were unaffected female carriers. The pedigree data were entirely compatible with the previously proposed X-linked susceptibility locus, with a gene frequency of .08, penetrance of .11 in heterozygous females, and 40% of affected females being homozygous, the remainder being explained by heterozygosity and disadvantageous X inactivation. PMID:7611298

  2. Revealing the prehistoric settlement of Australia by Y chromosome and mtDNA analysis

    PubMed Central

    Hudjashov, Georgi; Kivisild, Toomas; Underhill, Peter A.; Endicott, Phillip; Sanchez, Juan J.; Lin, Alice A.; Shen, Peidong; Oefner, Peter; Renfrew, Colin; Villems, Richard; Forster, Peter

    2007-01-01

    Published and new samples of Aboriginal Australians and Melanesians were analyzed for mtDNA (n = 172) and Y variation (n = 522), and the resulting profiles were compared with the branches known so far within the global mtDNA and the Y chromosome tree. (i) All Australian lineages are confirmed to fall within the mitochondrial founder branches M and N and the Y chromosomal founders C and F, which are associated with the exodus of modern humans from Africa ≈50–70,000 years ago. The analysis reveals no evidence for any archaic maternal or paternal lineages in Australians, despite some suggestively robust features in the Australian fossil record, thus weakening the argument for continuity with any earlier Homo erectus populations in Southeast Asia. (ii) The tree of complete mtDNA sequences shows that Aboriginal Australians are most closely related to the autochthonous populations of New Guinea/Melanesia, indicating that prehistoric Australia and New Guinea were occupied initially by one and the same Palaeolithic colonization event ≈50,000 years ago, in agreement with current archaeological evidence. (iii) The deep mtDNA and Y chromosomal branching patterns between Australia and most other populations around the Indian Ocean point to a considerable isolation after the initial arrival. (iv) We detect only minor secondary gene flow into Australia, and this could have taken place before the land bridge between Australia and New Guinea was submerged ≈8,000 years ago, thus calling into question that certain significant developments in later Australian prehistory (the emergence of a backed-blade lithic industry, and the linguistic dichotomy) were externally motivated. PMID:17496137

  3. Tracing European Founder Lineages in the Near Eastern mtDNA Pool

    PubMed Central

    Richards, Martin; Macaulay, Vincent; Hickey, Eileen; Vega, Emilce; Sykes, Bryan; Guida, Valentina; Rengo, Chiara; Sellitto, Daniele; Cruciani, Fulvio; Kivisild, Toomas; Villems, Richard; Thomas, Mark; Rychkov, Serge; Rychkov, Oksana; Rychkov, Yuri; Gölge, Mukaddes; Dimitrov, Dimitar; Hill, Emmeline; Bradley, Dan; Romano, Valentino; Calì, Francesco; Vona, Giuseppe; Demaine, Andrew; Papiha, Surinder; Triantaphyllidis, Costas; Stefanescu, Gheorghe; Hatina, Jiři; Belledi, Michele; Di Rienzo, Anna; Oppenheim, Ariella; Nørby, Søren; Al-Zaheri, Nadia; Santachiara-Benerecetti, Silvana; Scozzari, Rosaria; Torroni, Antonio; Bandelt, Hans-Jürgen

    2000-01-01

    Founder analysis is a method for analysis of nonrecombining DNA sequence data, with the aim of identification and dating of migrations into new territory. The method picks out founder sequence types in potential source populations and dates lineage clusters deriving from them in the settlement zone of interest. Here, using mtDNA, we apply the approach to the colonization of Europe, to estimate the proportion of modern lineages whose ancestors arrived during each major phase of settlement. To estimate the Palaeolithic and Neolithic contributions to European mtDNA diversity more accurately than was previously achievable, we have now extended the Near Eastern, European, and northern-Caucasus databases to 1,234, 2,804, and 208 samples, respectively. Both back-migration into the source population and recurrent mutation in the source and derived populations represent major obstacles to this approach. We have developed phylogenetic criteria to take account of both these factors, and we suggest a way to account for multiple dispersals of common sequence types. We conclude that (i) there has been substantial back-migration into the Near East, (ii) the majority of extant mtDNA lineages entered Europe in several waves during the Upper Palaeolithic, (iii) there was a founder effect or bottleneck associated with the Last Glacial Maximum, 20,000 years ago, from which derives the largest fraction of surviving lineages, and (iv) the immigrant Neolithic component is likely to comprise less than one-quarter of the mtDNA pool of modern Europeans. PMID:11032788

  4. Mass spectrometric base composition profiling: Implications for forensic mtDNA databasing☆

    PubMed Central

    Eduardoff, Mayra; Huber, Gabriela; Bayer, Birgit; Schmid, Dagmar; Anslinger, Katja; Göbel, Tanja; Zimmermann, Bettina; Schneider, Peter M.; Röck, Alexander W.; Parson, Walther

    2013-01-01

    In forensic genetics mitochondrial DNA (mtDNA) is usually analyzed by direct Sanger-type sequencing (STS). This method is known to be laborious and sometimes prone to human error. Alternative methods have been proposed that lead to faster results. Among these are methods that involve mass-spectrometry resulting in base composition profiles that are, by definition, less informative than the full nucleotide sequence. Here, we applied a highly automated electrospray ionization mass spectrometry (ESI-MS) system (PLEX-ID) to an mtDNA population study to compare its performance with respect to throughput and concordance to STS. We found that the loss of information power was relatively low compared to the gain in speed and analytical standardization. The detection of point and length heteroplasmy turned out to be roughly comparable between the technologies with some individual differences related to the processes. We confirm that ESI-MS provides a valuable platform for analyzing mtDNA variation that can also be applied in the forensic context. PMID:24054029

  5. Evaluating sequence-derived mtDNA length heteroplasmy by amplicon size analysis

    PubMed Central

    Berger, C.; Hatzer-Grubwieser, P.; Hohoff, C.; Parson, W.

    2011-01-01

    Length heteroplasmy (LH) in mitochondrial (mt)DNA is usually observed in homopolymeric tracts and manifest as mixture of various length variants. The generally used difference-coded annotation to report mtDNA haplotypes does not express the degree of LH variation present in a sample, even more so, it is sometimes difficult to establish which length variants are present and clearly distinguishable from background noise. It has therefore become routine practice for some researchers to call the dominant type, the “major molecule”, which represents the LH variant that is most abundant in a DNA extract. In the majority of cases a clear single dominant variant can be identified. However, in some samples this interpretation is difficult, i.e. when (almost) equally quantitative LH variants are present or when multiple sequencing primers result in the presentation of different dominant types. To better understand those cases we designed amplicon sizing assays for the five most relevant LH regions in the mtDNA control region (around ntps 16,189, 310, 460, 573, and the AC-repeat between 514 and 524) to determine the ratio of the LH variants by fluorescence based amplicon sizing assays. For difficult LH constellations derived by Sanger sequencing (with Big Dye terminators) these assays mostly gave clear and unambiguous results. In the vast majority of cases we found agreement between the results of the sequence and amplicon analyses and propose this alternative method in difficult cases. PMID:21067985

  6. Surveyor nuclease detection of mutations and polymorphisms of mtDNA in children.

    PubMed

    Pilch, Jacek; Asman, Marek; Jamroz, Ewa; Kajor, Maciej; Kotrys-Puchalska, Elżbieta; Goss, Małgorzata; Krzak, Maria; Witecka, Joanna; Gmiński, Jan; Sieroń, Aleksander L

    2010-11-01

    Mitochondrial encephalomyopathies are complex disorders with wide range of clinical manifestations. Particularly time-consuming is the identification of mutations in mitochondrial DNA. A group of 20 children with clinical manifestations of mitochondrial encephalomyopathies was selected for molecular studies. The aims were (a) to identify mutations in mtDNA isolated from muscle and (b) to verify detected mutations in DNA isolated from blood, in order to assess the utility of a Surveyor nuclease assay kit for patient screening. The most common changes found were polymorphisms, including a few missense mutations altering the amino acid sequence of mitochondrial proteins. In two boys with MELAS (i.e., mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes), a mutation A→G3243 was detected in the tRNALeu gene of mtDNA isolated from muscle and blood. In one boy, the carrier status of his mother was confirmed, based on molecular analysis of DNA isolated from blood. A method using Surveyor nuclease allows systematic screening for small mutations in mtDNA, using as its source blood of the patients and asymptomatic carriers. The method still requires confirmation studying a larger group. In some patients, the use of this method should precede and might limit indications for traumatic muscle and skin biopsy.

  7. Rapid deployment of the five founding Amerind mtDNA haplogroups via coastal and riverine colonization.

    PubMed

    Fix, Alan G

    2005-10-01

    Numerous studies of variation in mtDNA in Amerindian populations established that four haplogroups are present throughout both North and South America. These four haplogroups (A, B, C, and D) and perhaps a fifth (X) in North America are postulated to be present in the initial founding migration to the Americas. Furthermore, studies of ancient mtDNA in North America suggested long-term regional continuity of the frequencies of these founding haplogroups. Present-day tribal groups possess high frequencies of private mtDNA haplotypes (variants within the major haplogroups), consistent with early establishment of local isolation of regional populations. Clearly these patterns have implications for the mode of colonization of the hemisphere. Recently, the earlier consensus among archaeologists for an initial colonization by Clovis hunters arriving through an ice-free corridor and expanding in a "blitzkrieg " wave was shown to be inconsistent with extensive genetic variability in Native Americans; a coastal migration route avoids this problem. The present paper demonstrates through a computer simulation model how colonization along coasts and rivers could have rapidly spread the founding lineages widely through North America.

  8. Polynesian genetic affinities with Southeast Asian populations as identified by mtDNA analysis.

    PubMed Central

    Melton, T; Peterson, R; Redd, A J; Saha, N; Sofro, A S; Martinson, J; Stoneking, M

    1995-01-01

    Polynesian genetic affinities to populations of Asia were studied using mtDNA markers. A total of 1,037 individuals from 12 populations were screened for a 9-bp deletion in the intergenic region between the COII and tRNA(Lys) genes that approaches fixation in Polynesians. Sequence-specific oligonucleotide probes that identify specific mtDNA control region nucleotide substitutions were used to describe variation in individuals with the 9-bp deletion. The 9-bp deletion was not observed in northern Indians, Bangladeshis, or Pakistanis but was seen at low to moderate frequencies in the nine other Southeast Asian populations. Three substitutions in the control region at positions 16217, 16247, and 16261 have previously been observed at high frequency in Polynesian mtDNAs; this "Polynesian motif" was observed in 20% of east Indonesians with the 9-bp deletion but was observed in only one additional individual. mtDNA types related to the Polynesian motif are highest in frequency in the corridor from Taiwan south through the Philippines and east Indonesia, and the highest diversity for these types is in Taiwan. These results are consistent with linguistic evidence of a Taiwanese origin for the proto-Polynesian expansion, which spread throughout Oceania by way of Indonesia. PMID:7668267

  9. mtDNA and Y-chromosome polymorphisms in four Native American populations from southern Mexico.

    PubMed Central

    Torroni, A.; Chen, Y. S.; Semino, O.; Santachiara-Beneceretti, A. S.; Scott, C. R.; Lott, M. T.; Winter, M.; Wallace, D. C.

    1994-01-01

    mtDNA sequence variation was examined in 60 Native Americans (Mixtecs from the Alta, Mixtecs from the Baja, Valley Zapotecs, and Highland Mixe) from southern Mexico by PCR amplification and high-resolution restriction endonuclease analysis. Four groups of mtDNA haplotypes (haplogroups A, B, C, and D) characterize Amerind populations, but only three (haplogroups A, B, and C) were observed in these Mexican populations. The comparison of their mtDNA variation with that observed in other populations from Mexico and Central America permits a clear distinction among the different Middle American tribes and raises questions about some of their linguistic affiliations. The males of these population samples were also analyzed for Y-chromosome RFLPs with the probes 49a, 49f, and 12f2. This analysis suggests that certain Y-chromosome haplotypes were brought from Asia during the colonization of the Americas, and a differential gene flow was introduced into Native American populations from European males and females. Images Figure 4 PMID:8304347

  10. mtDNA variation in the Yanomami: evidence for additional New World founding lineages.

    PubMed Central

    Easton, R. D.; Merriwether, D. A.; Crews, D. E.; Ferrell, R. E.

    1996-01-01

    Native Americans have been classified into four founding haplogroups with as many as seven founding lineages based on mtDNA RFLPs and DNA sequence data. mtDNA analysis was completed for 83 Yanomami from eight villages in the Surucucu and Catrimani Plateau regions of Roraima in northwestern Brazil. Samples were typed for 15 polymorphic mtDNA sites (14 RFLP sites and 1 deletion site), and a subset was sequenced for both hypervariable regions of the mitochondrial D-loop. Substantial mitochondrial diversity was detected among the Yanomami, five of seven accepted founding haplotypes and three others were observed. Of the 83 samples, 4 (4.8%) were lineage B1, 1 (1.2%) was lineage B2, 31 (37.4%) were lineage C1, 29 (34.9%) were lineage C2, 2 (2.4%) were lineage D1, 6 (7.2%) were lineage D2, 7 (8.4%) were a haplotype we designated "X6," and 3 (3.6%) were a haplotype we designated "X7." Sequence analysis found 43 haplotypes in 50 samples. B2, X6, and X7 are previously unrecognized mitochondrial founding lineage types of Native Americans. The widespread distribution of these haplotypes in the New World and Asia provides support for declaring these lineages to be New World founding types. PMID:8659527

  11. mtDNA variation in the Yanomami: evidence for additional New World founding lineages.

    PubMed

    Easton, R D; Merriwether, D A; Crews, D E; Ferrell, R E

    1996-07-01

    Native Americans have been classified into four founding haplogroups with as many as seven founding lineages based on mtDNA RFLPs and DNA sequence data. mtDNA analysis was completed for 83 Yanomami from eight villages in the Surucucu and Catrimani Plateau regions of Roraima in northwestern Brazil. Samples were typed for 15 polymorphic mtDNA sites (14 RFLP sites and 1 deletion site), and a subset was sequenced for both hypervariable regions of the mitochondrial D-loop. Substantial mitochondrial diversity was detected among the Yanomami, five of seven accepted founding haplotypes and three others were observed. Of the 83 samples, 4 (4.8%) were lineage B1, 1 (1.2%) was lineage B2, 31 (37.4%) were lineage C1, 29 (34.9%) were lineage C2, 2 (2.4%) were lineage D1, 6 (7.2%) were lineage D2, 7 (8.4%) were a haplotype we designated "X6," and 3 (3.6%) were a haplotype we designated "X7." Sequence analysis found 43 haplotypes in 50 samples. B2, X6, and X7 are previously unrecognized mitochondrial founding lineage types of Native Americans. The widespread distribution of these haplotypes in the New World and Asia provides support for declaring these lineages to be New World founding types.

  12. Peopling of Sahul: mtDNA variation in aboriginal Australian and Papua New Guinean populations.

    PubMed Central

    Redd, A J; Stoneking, M

    1999-01-01

    We examined genetic affinities of Aboriginal Australian and New Guinean populations by using nucleotide variation in the two hypervariable segments of the mtDNA control region (CR). A total of 318 individuals from highland Papua New Guinea (PNG), coastal PNG, and Aboriginal Australian populations were typed with a panel of 29 sequence-specific oligonucleotide (SSO) probes. The SSO-probe panel included five new probes that were used to type an additional 1,037 individuals from several Asian populations. The SSO-type data guided the selection of 78 individuals from Australia and east Indonesia for CR sequencing. A gene tree of these CR sequences, combined with published sequences from worldwide populations, contains two previously identified highland PNG clusters that do not include any Aboriginal Australians; the highland PNG clusters have coalescent time estimates of approximately 80,000 and 122,000 years ago, suggesting ancient isolation and genetic drift. SSO-type data indicate that 84% of the sample of PNG highlander mtDNA belong to these two clusters. In contrast, the Aboriginal Australian sequences are intermingled throughout the tree and cluster with sequences from multiple populations. Phylogenetic and multidimensional-scaling analyses of CR sequences and SSO types split PNG highland and Aboriginal Australian populations and link Aboriginal Australian populations with populations from the subcontinent of India. These mtDNA results do not support a close relationship between Aboriginal Australian and PNG populations but instead suggest multiple migrations in the peopling of Sahul. PMID:10441589

  13. Detection of age-related duplications in mtDNA from human muscles and bones.

    PubMed

    Lacan, Marie; Thèves, Catherine; Keyser, Christine; Farrugia, Audrey; Baraybar, Jose-Pablo; Crubézy, Eric; Ludes, Bertrand

    2011-03-01

    Several studies have demonstrated the age-related accumulation of duplications in the D-loop of mitochondrial DNA (mtDNA) extracted from skeletal muscle. This kind of mutation had not yet been studied in bone. The detection of age-related mutations in bone tissue could help to estimate age at death within the context of legal medicine or/and anthropological identification procedures, when traditional osteological markers studied are absent or inefficient. As we detected an accumulation of a point mutation in mtDNA from an older individual's bones in a previous study, we tried here to identify if three reported duplications (150, 190, 260 bp) accumulate in this type of tissue. We developed a sensitive method which consists in the use of back-to-back primers during amplification followed by an electrophoresis capillary analysis. The aim of this study was to confirm that at least one duplication appears systematically in muscle tissue after the age of 20 and to evaluate the duplication age appearance in bones extracted from the same individuals. We found that the number of duplications increase from 38 years and that at least one duplicated fragment is present in 50% of cases after 70 years in this tissue. These results confirm that several age-related mutations can be detected in the D-loop of mtDNA and open the way for the use of molecular markers for age estimation in forensic and/or anthropological identification.

  14. Mass spectrometric base composition profiling: Implications for forensic mtDNA databasing.

    PubMed

    Eduardoff, Mayra; Huber, Gabriela; Bayer, Birgit; Schmid, Dagmar; Anslinger, Katja; Göbel, Tanja; Zimmermann, Bettina; Schneider, Peter M; Röck, Alexander W; Parson, Walther

    2013-12-01

    In forensic genetics mitochondrial DNA (mtDNA) is usually analyzed by direct Sanger-type sequencing (STS). This method is known to be laborious and sometimes prone to human error. Alternative methods have been proposed that lead to faster results. Among these are methods that involve mass-spectrometry resulting in base composition profiles that are, by definition, less informative than the full nucleotide sequence. Here, we applied a highly automated electrospray ionization mass spectrometry (ESI-MS) system (PLEX-ID) to an mtDNA population study to compare its performance with respect to throughput and concordance to STS. We found that the loss of information power was relatively low compared to the gain in speed and analytical standardization. The detection of point and length heteroplasmy turned out to be roughly comparable between the technologies with some individual differences related to the processes. We confirm that ESI-MS provides a valuable platform for analyzing mtDNA variation that can also be applied in the forensic context.

  15. The origin of Eastern European Jews revealed by autosomal, sex chromosomal and mtDNA polymorphisms

    PubMed Central

    2010-01-01

    Background This study aims to establish the likely origin of EEJ (Eastern European Jews) by genetic distance analysis of autosomal markers and haplogroups on the X and Y chromosomes and mtDNA. Results According to the autosomal polymorphisms the investigated Jewish populations do not share a common origin, and EEJ are closer to Italians in particular and to Europeans in general than to the other Jewish populations. The similarity of EEJ to Italians and Europeans is also supported by the X chromosomal haplogroups. In contrast according to the Y-chromosomal haplogroups EEJ are closest to the non-Jewish populations of the Eastern Mediterranean. MtDNA shows a mixed pattern, but overall EEJ are more distant from most populations and hold a marginal rather than a central position. The autosomal genetic distance matrix has a very high correlation (0.789) with geography, whereas the X-chromosomal, Y-chromosomal and mtDNA matrices have a lower correlation (0.540, 0.395 and 0.641 respectively). Conclusions The close genetic resemblance to Italians accords with the historical presumption that Ashkenazi Jews started their migrations across Europe in Italy and with historical evidence that conversion to Judaism was common in ancient Rome. The reasons for the discrepancy between the biparental markers and the uniparental markers are discussed. Reviewers This article was reviewed by Damian Labuda (nominated by Jerzy Jurka), Kateryna Makova and Qasim Ayub (nominated by Dan Graur). PMID:20925954

  16. Detection of mtDNA deletion in Pearson syndrome by two independent PCR assays from Guthrie card.

    PubMed

    Tóth, T; Bókay, J; Szönyi, L; Nagy, B; Papp, Z

    1998-03-01

    Pearson syndrome is a multisystem juvenile condition associated with deletions in the mitochondrial genome. The most common 4977 bp deletion of mitochondrial DNA (mtDNA) can mainly be detected in the patients' peripheral blood. Here we report a child with a clinically unclarified diagnosis where molecular genetic results proved Pearson syndrome from stored dried blood sample 6 months after the patient's death. PCR amplification around the breakpoint of the most common mtDNA deletion could detect the presence of mutated mtDNA. Another polymerase chain reaction (PCR) assay indicated the low level of wild type mtDNA in patients' blood. We believe that this case shows the importance of storing Guthrie card and the availability of detection of Pearson syndrome from dried blood sample.

  17. mtDNA mutations in human aging and longevity: controversies and new perspectives opened by high-throughput technologies.

    PubMed

    Sevini, Federica; Giuliani, Cristina; Vianello, Dario; Giampieri, Enrico; Santoro, Aurelia; Biondi, Fiammetta; Garagnani, Paolo; Passarino, Giuseppe; Luiselli, Donata; Capri, Miriam; Franceschi, Claudio; Salvioli, Stefano

    2014-08-01

    The last 30 years of research greatly contributed to shed light on the role of mitochondrial DNA (mtDNA) variability in aging, although contrasting results have been reported, mainly due to bias regarding the population size and stratification, and to the use of analysis methods (haplogroup classification) that resulted to be not sufficiently adequate to grasp the complexity of the phenomenon. A 5-years European study (the GEHA EU project) collected and analyzed data on mtDNA variability on an unprecedented number of long-living subjects (enriched for longevity genes) and a comparable number of controls (matched for gender and ethnicity) in Europe. This very large study allowed a reappraisal of the role of both the inherited and the somatic mtDNA variability in aging, as an association with longevity emerged only when mtDNA variants in OXPHOS complexes co-occurred. Moreover, the availability of data from both nuclear and mitochondrial genomes on a large number of subjects paves the way for an evaluation at a very large scale of the epistatic interactions at a higher level of complexity. This scenario is expected to be even more clarified in the next future with the use of next generation sequencing (NGS) techniques, which are becoming applicable to evaluate mtDNA variability and, then, new mathematical/bioinformatic analysis methods are urgently needed. Recent advances of association studies on age-related diseases and mtDNA variability will also be discussed in this review, taking into account the bias hidden by population stratification. Finally, very recent findings in terms of mtDNA heteroplasmy (i.e. the coexistence of wild type and mutated copies of mtDNA) and aging as well as mitochondrial epigenetic mechanisms will also be discussed.

  18. Selection of rodent species appropriate for mtDNA transfer to generate transmitochondrial mito-mice expressing mitochondrial respiration defects.

    PubMed

    Enoki, Shunkei; Shimizu, Akinori; Hayashi, Chisato; Imanishi, Hirotake; Hashizume, Osamu; Mekada, Kazuyuki; Suzuki, Hitoshi; Hashimoto, Tetsuo; Nakada, Kazuto; Hayashi, Jun-Ichi

    2014-01-01

    Previous reports have shown that transmitochondrial mito-mice with nuclear DNA from Mus musculus and mtDNA from M. spretus do not express respiration defects, whereas those with mtDNA from Rattus norvegicus cannot be generated from ES cybrids with mtDNA from R. norvegicus due to inducing significant respiration defects and resultant losing multipotency. Here, we isolated transmitochondrial cybrids with mtDNA from various rodent species classified between M. spretus and R. norvegicus, and compared the O2 consumption rates. The results showed a strong negative correlation between phylogenetic distance and reduction of O2 consumption rates, which would be due to the coevolution of nuclear and mitochondrial genomes and the resultant incompatibility between the nuclear genome from M. musculus and the mitochondrial genome from the other rodent species. These observations suggested that M. caroli was an appropriate mtDNA donor to generate transmitochondrial mito-mice with nuclear DNA from M. musculus. Then, we generated ES cybrids with M. caroli mtDNA, and found that these ES cybrids expressed respiration defects without losing multipotency and can be used to generate transmitochondrial mito-mice expressing mitochondrial disorders.

  19. mtDNA variation in caste populations of Andhra Pradesh, India.

    PubMed

    Bamshad, M; Fraley, A E; Crawford, M H; Cann, R L; Busi, B R; Naidu, J M; Jorde, L B

    1996-02-01

    Various anthropological analyses have documented extensive regional variation among populations on the subcontinent of India using morphological, protein, blood group, and nuclear DNA polymorphisms. These patterns are the product of complex population structure (genetic drift, gene flow) and a population history noted for numerous branching events. As a result, the interpretation of relationships among caste populations of South India and between Indians and continental populations remains controversial. The Hindu caste system is a general model of genetic differentiation among endogamous populations stratified by social forces (e.g., religion and occupation). The mitochondrial DNA (mtDNA) molecule has unique properties that facilitate the exploration of population structure. We analyzed 36 Hindu men born in Andhra Pradesh who were unrelated matrilineally through at least 3 generations and who represent 4 caste populations: Brahmin (9), Yadava (10), Kapu (7), and Relli (10). Individuals from Africa (36), Asia (36), and Europe (36) were sampled for comparison. A 200-base-pair segment of hypervariable segment 2 (HVS2) of the mtDNA control region was sequenced in all individuals. In the Indian castes 25 distinct haplotypes are identified. Aside from the Cambridge reference sequence, only two haplotypes are shared between caste populations. Middle castes form a highly supported cluster in a neighbor-joining network. Mean nucleotide diversity within each caste is 0.015, 0.012, 0.011, and 0.012 for the Brahmin, Yadava, Kapu, and Relli, respectively. mtDNA variation is highly structured between castes (GST = 0.17; p < 0.002). The effects of social structure on mtDNA variation are much greater than those on variation measured by traditional markers. Explanations for this discordance include (1) the higher resolving power of mtDNA, (2) sex-dependent gene flow, (3) differences in male and female effective population sizes, and (4) elements of the kinship structure. Thirty

  20. mtDNA haplogroup and single nucleotide polymorphisms structure human microbiome communities

    PubMed Central

    2014-01-01

    Background Although our microbial community and genomes (the human microbiome) outnumber our genome by several orders of magnitude, to what extent the human host genetic complement informs the microbiota composition is not clear. The Human Microbiome Project (HMP) Consortium established a unique population-scale framework with which to characterize the relationship of microbial community structure with their human hosts. A wide variety of taxa and metabolic pathways have been shown to be differentially distributed by virtue of race/ethnicity in the HMP. Given that mtDNA haplogroups are the maternally derived ancestral genomic markers and mitochondria’s role as the generator for cellular ATP, characterizing the relationship between human mtDNA genomic variants and microbiome profiles becomes of potential marked biologic and clinical interest. Results We leveraged sequencing data from the HMP to investigate the association between microbiome community structures with its own host mtDNA variants. 15 haplogroups and 631 mtDNA nucleotide polymorphisms (mean sequencing depth of 280X on the mitochondria genome) from 89 individuals participating in the HMP were accurately identified. 16S rRNA (V3-V5 region) sequencing generated microbiome taxonomy profiles and whole genome shotgun sequencing generated metabolic profiles from various body sites were treated as traits to conduct association analysis between haplogroups and host clinical metadata through linear regression. The mtSNPs of individuals with European haplogroups were associated with microbiome profiles using PLINK quantitative trait associations with permutation and adjusted for multiple comparisons. We observe that among 139 stool and 59 vaginal posterior fornix samples, several haplogroups show significant association with specific microbiota (q-value < 0.05) as well as their aggregate community structure (Chi-square with Monte Carlo, p < 0.005), which confirmed and expanded previous research on the

  1. Mitochondrial DNA integrity changes with age but does not correlate with learning performance in honey bees.

    PubMed

    Hystad, E M; Amdam, G V; Eide, L

    2014-01-01

    The honey bee is a well-established model organism to study aging, learning and memory. Here, we used young and old forager honey bees to investigate whether age-related learning capacity correlates with mitochondrial function. The bees were selected for age and learning performance and mitochondrial function was evaluated by measuring mtDNA integrity, mtDNA copy number and mitochondrial gene expression. Quite unexpectedly, mtDNA from young bees showed more damage than mtDNA from older bees, but neither mtDNA integrity, nor mtDNA copy number nor mitochondrial gene expression correlated with learning performance. Although not statistically significant (p=0.07) the level of L-rRNA increased with age in good learners whereas it decreased in poor learners. Our results show that learning performance in honey bee does not correlate with absolute mitochondrial parameters like mtDNA damage, copy number or expression of mitochondrial genes, but may be associated with the ability to regulate mitochondrial activity.

  2. Association of AluYb8 insertion/deletion polymorphism in the MUTYH gene with mtDNA maintain in the type 2 diabetes mellitus patients.

    PubMed

    Guo, Wenwen; Zheng, Bixia; Guo, Dong; Cai, Zhenming; Wang, Yaping

    2015-07-05

    A common AluYb8-element insertion/deletion polymorphism of the MUTYH gene (AluYb8MUTYH) is a novel genetic risk factor for type 2 diabetes mellitus (T2DM). In the present study, mtDNA sequencing analysis indicated that the mtDNA sequence heteroplasmy was not associated with AluYb8MUTYH polymorphism. To better understand the genetic risk for T2DM, we investigated the association of this polymorphism with mtDNA content, mtDNA breakage and mtDNA transcription in the leukocytes of T2DM patients. The mtDNA content and unbroken mtDNA were significantly increased in the mutant patients than in the wild-type patients (P <0.05, respectively). However, no association between mtDNA transcription and AluYb8MUTYH variant was observed. The results suggested that the AluYb8MUTYH variant was associated with an altered mtDNA maintain in T2DM patients. The high level of mtDNA content observed in the mutant patients may have resulted from inefficient base excision repair of mitochondrial MUTYH and a compensatory mechanism that is triggered by elevated oxidative stress.

  3. Near-complete elimination of mutant mtDNA by iterative or dynamic dose-controlled treatment with mtZFNs

    PubMed Central

    Gammage, Payam A.; Gaude, Edoardo; Van Haute, Lindsey; Rebelo-Guiomar, Pedro; Jackson, Christopher B.; Rorbach, Joanna; Pekalski, Marcin L.; Robinson, Alan J.; Charpentier, Marine; Concordet, Jean-Paul; Frezza, Christian; Minczuk, Michal

    2016-01-01

    Mitochondrial diseases are frequently associated with mutations in mitochondrial DNA (mtDNA). In most cases, mutant and wild-type mtDNAs coexist, resulting in heteroplasmy. The selective elimination of mutant mtDNA, and consequent enrichment of wild-type mtDNA, can rescue pathological phenotypes in heteroplasmic cells. Use of the mitochondrially targeted zinc finger-nuclease (mtZFN) results in degradation of mutant mtDNA through site-specific DNA cleavage. Here, we describe a substantial enhancement of our previous mtZFN-based approaches to targeting mtDNA, allowing near-complete directional shifts of mtDNA heteroplasmy, either by iterative treatment or through finely controlled expression of mtZFN, which limits off-target catalysis and undesired mtDNA copy number depletion. To demonstrate the utility of this improved approach, we generated an isogenic distribution of heteroplasmic cells with variable mtDNA mutant level from the same parental source without clonal selection. Analysis of these populations demonstrated an altered metabolic signature in cells harbouring decreased levels of mutant m.8993T>G mtDNA, associated with neuropathy, ataxia, and retinitis pigmentosa (NARP). We conclude that mtZFN-based approaches offer means for mtDNA heteroplasmy manipulation in basic research, and may provide a strategy for therapeutic intervention in selected mitochondrial diseases. PMID:27466392

  4. Clustering of Caucasian Leber hereditary optic neuropathy patients containing the 11778 or 14484 mutations on an mtDNA lineage

    SciTech Connect

    Brown, M.D.; Sun, F.; Wallace, D.C.

    1997-02-01

    Leber hereditary optic neuropathy (LHON) is a type of blindness caused by mtDNA mutations. Three LHON mtDNA mutations at nucleotide positions 3460, 11778, and 14484 are specific for LHON and account for 90% of worldwide cases and are thus designated as {open_quotes}primary{close_quotes} LHON mutations. Fifteen other {open_quotes}secondary{close_quotes} LHON mtDNA mutations have been identified, but their pathogenicity is unclear. mtDNA haplotype and phylogenetic analysis of the primary LHON mutations in North American Caucasian patients and controls has shown that, unlike the 3460 and 11778 mutations, which are distributed throughout the European-derived (Caucasian) mtDNA phylogeny, patients containing the 14484 mutation tended to be associated with European mtDNA haplotype J. To investigate this apparent clustering, we performed {chi}{sup 2}-based statistical analyses to compare the distribution of LHON patients on the Caucasian phylogenetic tree. Our results indicate that, unlike the 3460 and 11778 mutations, the 14484 mutation was not distributed on the phylogeny in proportion to the frequencies of the major Caucasian mtDNA haplogroups found in North America. The 14484 mutation was next shown to occur on the haplogroup J background more frequently that expected, consistent with the observation that {approximately}75% of worldwide 14484-positive LHON patients occur in association with haplogroup J. The 11778 mutation also exhibited a moderate clustering on haplogroup J. These observations were supported by statistical analysis using all available mutation frequencies reported in the literature. This paper thus illustrates the potential importance of genetic background in certain mtDNA-based diseases, speculates on a pathogenic role for a subset of LHON secondary mutations and their interaction with primary mutations, and provides support for a polygenic model for LHON expression in some cases. 18 refs., 3 tabs.

  5. Mutations in TFAM, encoding mitochondrial transcription factor A, cause neonatal liver failure associated with mtDNA depletion.

    PubMed

    Stiles, Ashlee R; Simon, Mariella T; Stover, Alexander; Eftekharian, Shaya; Khanlou, Negar; Wang, Hanlin L; Magaki, Shino; Lee, Hane; Partynski, Kate; Dorrani, Nagmeh; Chang, Richard; Martinez-Agosto, Julian A; Abdenur, Jose E

    2016-09-01

    In humans, mitochondrial DNA (mtDNA) depletion syndromes are a group of genetically and clinically heterogeneous autosomal recessive disorders that arise as a consequence of defects in mtDNA replication or nucleotide synthesis. Clinical manifestations are variable and include myopathic, encephalomyopathic, neurogastrointestinal or hepatocerebral phenotypes. Through clinical exome sequencing, we identified a homozygous missense variant (c.533C>T; p.Pro178Leu) in mitochondrial transcription factor A (TFAM) segregating in a consanguineous kindred of Colombian-Basque descent in which two siblings presented with IUGR, elevated transaminases, conjugated hyperbilirubinemia and hypoglycemia with progression to liver failure and death in early infancy. Results of the liver biopsy in the proband revealed cirrhosis, micro- and macrovesicular steatosis, cholestasis and mitochondrial pleomorphism. Electron microscopy of muscle revealed abnormal mitochondrial morphology and distribution while enzyme histochemistry was underwhelming. Electron transport chain testing in muscle showed increased citrate synthase activity suggesting mitochondrial proliferation, while respiratory chain activities were at the lower end of normal. mtDNA content was reduced in liver and muscle (11% and 21% of normal controls respectively). While Tfam mRNA expression was upregulated in primary fibroblasts, Tfam protein level was significantly reduced. Furthermore, functional investigations of the mitochondria revealed reduced basal respiration and spare respiratory capacity, decreased mtDNA copy number and markedly reduced nucleoids. TFAM is essential for transcription, replication and packaging of mtDNA into nucleoids. Tfam knockout mice display embryonic lethality secondary to severe mtDNA depletion. In this report, for the first time, we associate a homozygous variant in TFAM with a novel mtDNA depletion syndrome.

  6. Homopolymeric tract heteroplasmy in mtDNA from tissues and single oocytes: Support for a genetic bottleneck

    SciTech Connect

    Marchington, D.R.; Hartshorne, G.M.; Barlow, D.; Poulton, J.

    1997-02-01

    While mtDNA polymorphisms at single base positions are common, the overwhelming majority of the mitochondrial genomes within a single individual are usually identical. When there is a point-mutation difference between a mother and her offspring, there may be a complete switching of mtDNA type within a single generation. It is generally assumed that there is a genetic bottleneck whereby a single or small number of founder mtDNA(s) populate the organism, but it is not known at which stages the restriction/amplification of mtDNA subtype(s) occur, and this uncertainty impedes antenatal diagnosis for mtDNA disorders. Length polymorphisms in homopolymeric tracts have been demonstrated in the large noncoding region of mtDNA. We have developed a new method, T-PCR (trimmed PCR), to quantitate heteroplasmy for two of these tracts (D310 and D16189). D310 variation is sufficient to indicate clonal origins of tissues and single oocytes. Tissues from normal individuals often possessed more than one length variant (heteroplasmy). However, there was no difference in the pattern of the length variants between somatic tissues in any control individual when bulk samples were taken. Oocytes from normal women undergoing in vitro fertilization were frequently heteroplasmic for length variants, and in two cases the modal length of the D310 tract differed in individual oocytes from the same woman. These data suggest that a restriction/amplification event, which we attribute to clonal expansion of founder mtDNA(s), has occurred by the time oocytes are mature, although further segregation may occur at a later stage. In contrast to controls, the length distribution of the D310 tract varied between tissues in a patient with heteroplasmic mtDNA rearrangements, suggesting that these mutants influence segregation. These findings have important implications for the genetic counselling of patients with pathogenic mtDNA mutations. 21 refs., 5 figs., 1 tab.

  7. FGF21 is a biomarker for mitochondrial translation and mtDNA maintenance disorders

    PubMed Central

    Lehtonen, Jenni M.; Forsström, Saara; Bottani, Emanuela; Viscomi, Carlo; Baris, Olivier R.; Isoniemi, Helena; Höckerstedt, Krister; Österlund, Pia; Hurme, Mikko; Jylhävä, Juulia; Leppä, Sirpa; Markkula, Ritva; Heliö, Tiina; Mombelli, Giuliana; Uusimaa, Johanna; Laaksonen, Reijo; Laaksovirta, Hannu; Auranen, Mari; Zeviani, Massimo; Smeitink, Jan; Wiesner, Rudolf J.; Nakada, Kazuto; Isohanni, Pirjo

    2016-01-01

    Objective: To validate new mitochondrial myopathy serum biomarkers for diagnostic use. Methods: We analyzed serum FGF21 (S-FGF21) and GDF15 from patients with (1) mitochondrial diseases and (2) nonmitochondrial disorders partially overlapping with mitochondrial disorder phenotypes. We (3) did a meta-analysis of S-FGF21 in mitochondrial disease and (4) analyzed S-Fgf21 and skeletal muscle Fgf21 expression in 6 mouse models with different muscle-manifesting mitochondrial dysfunctions. Results: We report that S-FGF21 consistently increases in primary mitochondrial myopathy, especially in patients with mitochondrial translation defects or mitochondrial DNA (mtDNA) deletions (675 and 347 pg/mL, respectively; controls: 66 pg/mL, p < 0.0001 for both). This is corroborated in mice (mtDNA deletions 1,163 vs 379 pg/mL, p < 0.0001). However, patients and mice with structural respiratory chain subunit or assembly factor defects showed low induction (human 335 pg/mL, p < 0.05; mice 335 pg/mL, not significant). Overall specificities of FGF21 and GDF15 to find patients with mitochondrial myopathy were 89.3% vs 86.4%, and sensitivities 67.3% and 76.0%, respectively. However, GDF15 was increased also in a wide range of nonmitochondrial conditions. Conclusions: S-FGF21 is a specific biomarker for muscle-manifesting defects of mitochondrial translation, including mitochondrial transfer-RNA mutations and primary and secondary mtDNA deletions, the most common causes of mitochondrial disease. However, normal S-FGF21 does not exclude structural respiratory chain complex or assembly factor defects, important to acknowledge in diagnostics. Classification of evidence: This study provides Class III evidence that elevated S-FGF21 accurately distinguishes patients with mitochondrial myopathies from patients with other conditions, and FGF21 and GDF15 mitochondrial myopathy from other myopathies. PMID:27794108

  8. Causes and Consequences of Rapidly Evolving mtDNA in a Plant Lineage

    PubMed Central

    Trapp, Paul; Miller, Christopher M.; Bazos, Ioannis

    2017-01-01

    Understanding mechanisms of coevolution between nuclear and mitochondrial (mt) genomes is a defining challenge in eukaryotic genetics. The angiosperm genus Silene is a natural system to investigate the causes and consequences of mt mutation rate variation because closely related species have highly divergent rates. In Silene species with fast-evolving mtDNA, nuclear genes that encode mitochondrially targeted proteins (N-mt genes) are also fast-evolving. This correlation could indicate positive selection to compensate for mt mutations, but might also result from a recent relaxation of selection. To differentiate between these interpretations, we used phylogenetic and population-genetic methods to test for positive and relaxed selection in three classes of N-mt genes (oxidative phosphorylation genes, ribosomal genes, and “RRR” genes involved in mtDNA recombination, replication, and repair). In all three classes, we found that species with fast-evolving mtDNA had: 1) elevated dN/dS, 2) an excess of nonsynonymous divergence relative to levels of intraspecific polymorphism, which is a signature of positive selection, and 3) no clear signals of relaxed selection. “Control” genes exhibited comparatively few signs of positive selection. These results suggest that high mt mutation rates can create selection on N-mt genes and that relaxed selection is an unlikely cause of recent accelerations in the evolution of N-mt genes. Because mt-RRR genes were found to be under positive selection, it is unlikely that elevated mt mutation rates in Silene were caused by inactivation of these mt-RRR genes. Therefore, the causes of extreme increases in angiosperm mt mutation rates remain uncertain. PMID:28164243

  9. mtDNA haplogroup J Modulates telomere length and Nitric Oxide production

    PubMed Central

    2011-01-01

    Background Oxidative stress due to the overproduction of nitric oxide (NO) and other oxygen reactive species (ROS), play a main role in the initiation and progression of the OA disease and leads to the degeneration of mitochondria. Therefore, the goal of this work is to describe the difference in telomere length of peripheral blood leukocytes (PBLs) and Nitric Oxide (NO) production between mitochondrial DNA (mtDNA) haplogroup J and non-J carriers, as indirect approaches of oxidative stress. Methods The telomere length of PBL was analyzed in DNA samples from 166 healthy controls (114 J and 52 non-J) and 79 OA patients (41 J and 38 non-J) by means of a validated qPCR method. The NO production was assessed in 7 carriers of the haplogroup J and 27 non-J carriers, by means of the colorimetric reaction of the Griess reagent in supernatants of cultured chondrocytes. Inducible nitric oxide synthase (iNOS) mRNA from these samples was analyzed by qPCR. Appropiated statistical analyses were performed Results Carriers of the haplogroup J showed a significantly longer telomere length of PBLs than non-J carriers, regardless of age, gender and diagnosis (p = 0.025). Cultured chondrocytes carrying the mtDNA haplogroup J also showed a lower NO production than non-J carriers (p = 0.043). No significant correlations between age and telomore length of PBLs were detected neither for carriers of the haplogroup J nor for non-J carriers. A strong positive correlation between NO production and iNOS expression was also observed (correlation coefficient = 0.791, p < 0.001). Conclusion The protective effect of the mtDNA haplogroup J in the OA disease arise from a lower oxidative stress in carriers of this haplogroup, since this haplogroup is related to lower NO production and hence longer telomere length of PBLs too. PMID:22171676

  10. Deep mtDNA divergences indicate cryptic species in a fig-pollinating wasp

    PubMed Central

    Haine, Eleanor R; Martin, Joanne; Cook, James M

    2006-01-01

    Background Figs and fig-pollinating wasps are obligate mutualists that have coevolved for ca 90 million years. They have radiated together, but do not show strict cospeciation. In particular, it is now clear that many fig species host two wasp species, so there is more wasp speciation than fig speciation. However, little is known about how fig wasps speciate. Results We studied variation in 71 fig-pollinating wasps from across the large geographic range of Ficus rubiginosa in Australia. All wasps sampled belong to one morphological species (Pleistodontes imperialis), but we found four deep mtDNA clades that differed from each other by 9–17% nucleotides. As these genetic distances exceed those normally found within species and overlap those (10–26%) found between morphologically distinct Pleistodontes species, they strongly suggest cryptic fig wasp species. mtDNA clade diversity declines from all four present in Northern Queensland to just one in Sydney, near the southern range limit. However, at most sites multiple clades coexist and can be found in the same tree or even the same fig fruit and there is no evidence for parallel sub-division of the host fig species. Both mtDNA data and sequences from two nuclear genes support the monophyly of the "P. imperialis complex" relative to other Pleistodontes species, suggesting that fig wasp divergence has occurred without any host plant shift. Wasps in clade 3 were infected by a single strain (W1) of Wolbachia bacteria, while those in other clades carried a double infection (W2+W3) of two other strains. Conclusion Our study indicates that cryptic fig-pollinating wasp species have developed on a single host plant species, without the involvement of host plant shifts, or parallel host plant divergence. Despite extensive evidence for coevolution between figs and fig wasps, wasp speciation may not always be linked strongly with fig speciation. PMID:17040562

  11. Admixture estimates for Caracas, Venezuela, based on autosomal, Y-chromosome, and mtDNA markers.

    PubMed

    Martínez, Helios; Rodríguez-Larralde, Alvaro; Izaguirre, Mary Helen; De Guerra, Dinorah Castro

    2007-04-01

    The present Venezuelan population is the product of admixture of Amerindians, Europeans, and Africans, a process that was not homogeneous throughout the country. Blood groups, short tandem repeats (STRs), mtDNA, and Y-chromosome markers have been used successfully in admixture studies, but few such studies have been conducted in Venezuela. In this study we aim to estimate the admixture components of samples from two different socioeconomic levels from Caracas, Venezuela's capital city, compare their differences, and infer sexual asymmetry in the European Amerindian union patterns. Gene frequencies for blood groups ABO and Rh (CDE) and for the STRs VWA, F13A01, and FES/FPS and mtDNA and Y-chromosome haplogroups were studied in a sample of 60 individuals living in Caracas, taken from a private clinic (high socioeconomic level), and 50 individuals, also living in Caracas, drawn from a public maternity clinic (low socioeconomic level). The admixture analysis for the five autosomal markers gives a high European component (0.78) and an almost negligible African sub-Saharan component (0.06) for the high socioeconomic level, whereas for the low socioeconomic level the sub-Saharan, European, and Amerindian components were 0.21, 0.42, and 0.36, respectively. Estimates of admixture based on mtDNA and Y-chromosome markers reveal that the Amerindian contribution to these Caracas samples is almost entirely through females, because the Y-chromosome Amerindian and African sub-Saharan chromosomes found in this study were scarce. Our study reveals that the identification of the grandparents' geographic origin is an important methodological aspect to take into account in genetic studies related to the reconstruction of historical events.

  12. MtDNA analysis reveals enriched pathogenic mutations in Tibetan highlanders

    PubMed Central

    Kang, Longli; Zheng, Hong-Xiang; Zhang, Menghan; Yan, Shi; Li, Lei; Liu, Lijun; Liu, Kai; Hu, Kang; Chen, Feng; Ma, Lifeng; Qin, Zhendong; Wang, Yi; Wang, Xiaofeng; Jin, Li

    2016-01-01

    Tibetan highlanders, including Tibetans, Monpas, Lhobas, Dengs and Sherpas, are considered highly adaptive to severe hypoxic environments. Mitochondrial DNA (mtDNA) might be important in hypoxia adaptation given its role in coding core subunits of oxidative phosphorylation. In this study, we employed 549 complete highlander mtDNA sequences (including 432 random samples) to obtain a comprehensive view of highlander mtDNA profile. In the phylogeny of a total of 36,914 sequences, we identified 21 major haplogroups representing founding events of highlanders, most of which were coalesced in 10 kya. Through founder analysis, we proposed a three-phase model of colonizing the plateau, i.e., pre-LGM Time (30 kya, 4.68%), post-LGM Paleolithic Time (16.8 kya, 29.31%) and Neolithic Time (after 8 kya, 66.01% in total). We observed that pathogenic mutations occurred far more frequently in 22 highlander-specific lineages (five lineages carrying two pathogenic mutations and six carrying one) than in the 6,857 haplogroups of all the 36,914 sequences (P = 4.87 × 10−8). Furthermore, the number of possible pathogenic mutations carried by highlanders (in average 3.18 ± 1.27) were significantly higher than that in controls (2.82 ± 1.40) (P = 1.89 × 10−4). Considering that function-altering and pathogenic mutations are enriched in highlanders, we therefore hypothesize that they may have played a role in hypoxia adaptation. PMID:27498855

  13. mtDNA haplogroup X: An ancient link between Europe/Western Asia and North America?

    PubMed Central

    Brown, M D; Hosseini, S H; Torroni, A; Bandelt, H J; Allen, J C; Schurr, T G; Scozzari, R; Cruciani, F; Wallace, D C

    1998-01-01

    On the basis of comprehensive RFLP analysis, it has been inferred that approximately 97% of Native American mtDNAs belong to one of four major founding mtDNA lineages, designated haplogroups "A"-"D." It has been proposed that a fifth mtDNA haplogroup (haplogroup X) represents a minor founding lineage in Native Americans. Unlike haplogroups A-D, haplogroup X is also found at low frequencies in modern European populations. To investigate the origins, diversity, and continental relationships of this haplogroup, we performed mtDNA high-resolution RFLP and complete control region (CR) sequence analysis on 22 putative Native American haplogroup X and 14 putative European haplogroup X mtDNAs. The results identified a consensus haplogroup X motif that characterizes our European and Native American samples. Among Native Americans, haplogroup X appears to be essentially restricted to northern Amerindian groups, including the Ojibwa, the Nuu-Chah-Nulth, the Sioux, and the Yakima, although we also observed this haplogroup in the Na-Dene-speaking Navajo. Median network analysis indicated that European and Native American haplogroup X mtDNAs, although distinct, nevertheless are distantly related to each other. Time estimates for the arrival of X in North America are 12,000-36,000 years ago, depending on the number of assumed founders, thus supporting the conclusion that the peoples harboring haplogroup X were among the original founders of Native American populations. To date, haplogroup X has not been unambiguously identified in Asia, raising the possibility that some Native American founders were of Caucasian ancestry. PMID:9837837

  14. Phylogenetic analysis of Sicilian goats reveals a new mtDNA lineage.

    PubMed

    Sardina, M T; Ballester, M; Marmi, J; Finocchiaro, R; van Kaam, J B C H M; Portolano, B; Folch, J M

    2006-08-01

    The mitochondrial hypervariable region 1 (HVR1) sequence of 67 goats belonging to the Girgentana, Maltese and Derivata di Siria breeds was partially sequenced in order to present the first phylogenetic characterization of Sicilian goat breeds. These sequences were compared with published sequences of Indian and Pakistani domestic goats and wild goats. Mitochondrial lineage A was observed in most of the Sicilian goats. However, three Girgentana haplotypes were highly divergent from the Capra hircus clade, indicating that a new mtDNA lineage in domestic goats was found.

  15. Complete genome sequence of mitochondrial DNA (mtDNA) of Chlorella sorokiniana.

    PubMed

    Orsini, Massimiliano; Costelli, Cristina; Malavasi, Veronica; Cusano, Roberto; Concas, Alessandro; Angius, Andrea; Cao, Giacomo

    2016-01-01

    The complete sequence of mitochondrial genome of the Chlorella sorokiniana strain (SAG 111-8 k) is presented in this work. Within the Chlorella genus, it represents the second species with a complete sequenced and annotated mitochondrial genome (GenBank accession no. KM241869). The genome consists of circular chromosomes of 52,528 bp and encodes a total of 31 protein coding genes, 3 rRNAs and 26 tRNAs. The overall AT contents of the C. sorokiniana mtDNA is 70.89%, while the coding sequence is of 97.4%.

  16. Late Pleistocene human skeleton and mtDNA link Paleoamericans and modern Native Americans.

    PubMed

    Chatters, James C; Kennett, Douglas J; Asmerom, Yemane; Kemp, Brian M; Polyak, Victor; Blank, Alberto Nava; Beddows, Patricia A; Reinhardt, Eduard; Arroyo-Cabrales, Joaquin; Bolnick, Deborah A; Malhi, Ripan S; Culleton, Brendan J; Erreguerena, Pilar Luna; Rissolo, Dominique; Morell-Hart, Shanti; Stafford, Thomas W

    2014-05-16

    Because of differences in craniofacial morphology and dentition between the earliest American skeletons and modern Native Americans, separate origins have been postulated for them, despite genetic evidence to the contrary. We describe a near-complete human skeleton with an intact cranium and preserved DNA found with extinct fauna in a submerged cave on Mexico's Yucatan Peninsula. This skeleton dates to between 13,000 and 12,000 calendar years ago and has Paleoamerican craniofacial characteristics and a Beringian-derived mitochondrial DNA (mtDNA) haplogroup (D1). Thus, the differences between Paleoamericans and Native Americans probably resulted from in situ evolution rather than separate ancestry.

  17. The GHEP–EMPOP collaboration on mtDNA population data—A new resource for forensic casework

    PubMed Central

    Prieto, L.; Zimmermann, B.; Goios, A.; Rodriguez-Monge, A.; Paneto, G.G.; Alves, C.; Alonso, A.; Fridman, C.; Cardoso, S.; Lima, G.; Anjos, M.J.; Whittle, M.R.; Montesino, M.; Cicarelli, R.M.B.; Rocha, A.M.; Albarrán, C.; de Pancorbo, M.M.; Pinheiro, M.F.; Carvalho, M.; Sumita, D.R.; Parson, W.

    2011-01-01

    Mitochondrial DNA (mtDNA) population data for forensic purposes are still scarce for some populations, which may limit the evaluation of forensic evidence especially when the rarity of a haplotype needs to be determined in a database search. In order to improve the collection of mtDNA lineages from the Iberian and South American subcontinents, we here report the results of a collaborative study involving nine laboratories from the Spanish and Portuguese Speaking Working Group of the International Society for Forensic Genetics (GHEP-ISFG) and EMPOP. The individual laboratories contributed population data that were generated throughout the past 10 years, but in the majority of cases have not been made available to the scientific community. A total of 1019 haplotypes from Iberia (Basque Country, 2 general Spanish populations, 2 North and 1 Central Portugal populations), and Latin America (3 populations from São Paulo) were collected, reviewed and harmonized according to defined EMPOP criteria. The majority of data ambiguities that were found during the reviewing process (41 in total) were transcription errors confirming that the documentation process is still the most error-prone stage in reporting mtDNA population data, especially when performed manually. This GHEP–EMPOP collaboration has significantly improved the quality of the individual mtDNA datasets and adds mtDNA population data as valuable resource to the EMPOP database (www.empop.org). PMID:21075696

  18. MtDNA T4216C variation in multiple sclerosis: a systematic review and meta-analysis.

    PubMed

    Andalib, Sasan; Emamhadi, Mohammadreza; Yousefzadeh-Chabok, Shahrokh; Salari, Arsalan; Sigaroudi, Abdolhosein Emami; Vafaee, Manouchehr Seyedi

    2016-12-01

    MtDNA T4216C variation has frequently been investigated in Multiple Sclerosis (MS) patients; nonetheless, controversy has existed about the evidence of association of this variation with susceptibility to MS. The present systematic review and meta-analysis converge the results of the preceding publications, pertaining to association of mtDNA T4216C variation with susceptibility to MS, into a common conclusion. A computerized literature search in English was carried out to retrieve relevant publications from which required data were extracted. Using a fixed effect model, pooled odds ratio (OR), 95 % confidence interval (95 % CI), and P value were calculated for association of mtDNA T4216C variation with susceptibility to MS. The pooled results showed that there was a significant association between mtDNA T4216C variation and MS (OR = 1.38, 95 % CI = 1.13-1.67, P = 0.001). The present systematic review and meta-analysis suggest that mtDNA T4216C variation is a contributory factor in susceptibility to MS.

  19. Cross-strand binding of TFAM to a single mtDNA molecule forms the mitochondrial nucleoid.

    PubMed

    Kukat, Christian; Davies, Karen M; Wurm, Christian A; Spåhr, Henrik; Bonekamp, Nina A; Kühl, Inge; Joos, Friederike; Polosa, Paola Loguercio; Park, Chan Bae; Posse, Viktor; Falkenberg, Maria; Jakobs, Stefan; Kühlbrandt, Werner; Larsson, Nils-Göran

    2015-09-08

    Mammalian mitochondrial DNA (mtDNA) is packaged by mitochondrial transcription factor A (TFAM) into mitochondrial nucleoids that are of key importance in controlling the transmission and expression of mtDNA. Nucleoid ultrastructure is poorly defined, and therefore we used a combination of biochemistry, superresolution microscopy, and electron microscopy to show that mitochondrial nucleoids have an irregular ellipsoidal shape and typically contain a single copy of mtDNA. Rotary shadowing electron microscopy revealed that nucleoid formation in vitro is a multistep process initiated by TFAM aggregation and cross-strand binding. Superresolution microscopy of cultivated cells showed that increased mtDNA copy number increases nucleoid numbers without altering their sizes. Electron cryo-tomography visualized nucleoids at high resolution in isolated mammalian mitochondria and confirmed the sizes observed by superresolution microscopy of cell lines. We conclude that the fundamental organizational unit of the mitochondrial nucleoid is a single copy of mtDNA compacted by TFAM, and we suggest a packaging mechanism.

  20. Cladistic analysis of Heliconius butterflies and relatives (Nymphalidae: Heliconiiti): a revised phylogenetic position for Eueides based on sequences from mtDNA and a nuclear gene

    PubMed Central

    Brower, A. V. Z.; Egan, M. G.

    1997-01-01

    A new phylogenetic hypothesis for Heliconius and related genera is presented, based on DNA sequence data from mtDNA combined with a region of the wingless gene. This study also adds eight new taxa to a previous cladistic hypothesis based on the mtDNA alone. Simultaneous phylogenetic analysis of the two gene regions together supports a topology largely in agreement with traditional views of heliconiine relationships based on morphology and suggests that the mtDNA support for the sister relationship between Eueides and H. charithonia is due to convergent evolution of homoplasious mtDNA sites.

  1. Shipwrecks and founder effects: divergent demographic histories reflected in Caribbean mtDNA.

    PubMed

    Salas, Antonio; Richards, Martin; Lareu, María-Victoria; Sobrino, Beatriz; Silva, Sandra; Matamoros, Mireya; Macaulay, Vincent; Carracedo, Angel

    2005-12-01

    During the period of the Atlantic slave trade (15th-19th centuries), millions of people were forced to move from Africa to many American destinations, changing dramatically the human landscape of the Americas. Here, we analyze mitochondrial DNA from two different American populations with African ancestry, with hitherto unknown European and Native American components. On the basis of historical records, African-Americans from Chocó (Colombia) and the Garífunas (or "Black Carib") of Honduras are likely to have had very different demographic histories, with a significant founder effect in the formation of the latter. Both the common features and differences are reflected in their mtDNA composition. Both show a minor component (approximately 16%) from Native Central/South Americans and a larger component (approximately 84%) from sub-Saharan Africans. The latter component is very diverse in the African-Americans from Chocó, similar to that of sub-Saharan Africans, but much less so in the Garífunas, with several mtDNA types elevated to high frequency, suggesting the action of genetic drift.

  2. Molecular Characterization of Sudanese and Southern Sudanese Chicken Breeds Using mtDNA D-Loop.

    PubMed

    Wani, Charles E; Yousif, Ibrahim A; Ibrahim, Muntasir E; Musa, Hassan H

    2014-01-01

    The objective of this study was to assess the genetic relationships and diversity and to estimate the amount of gene flow among the five chicken populations from Sudan and South Sudan and commercial strain of egg line White Leghorn chickens. The chicken populations were genotyped using mtDNA D-loop as a molecular marker. PCR product of the mtDNA D-loop segment was 600 bp and 14 haplotypes were identified. The neighbor-joining phylogenetic tree indicated that the indigenous Sudanese chickens can be grouped into two clades, IV and IIIa only. Median joining networks analysis showed that haplotype LBB49 has the highest frequency. The hierarchal analysis of molecular variance (AMOVA) showed that genetic variation within the population was 88.6% and the differentiation among the population was 11.4%. When the populations was redefined into two geographical zones, rich and poor Savanna, the results were fractioned into three genetic variations: between individuals within population 95.5%, between populations within the group 0.75%, and genetic variation between groups 3.75%. The pair wise F st showed high genetic difference between Betwil populations and the rest with F st ranging from 0.1492 to 0.2447. We found that there is large number of gene exchanges within the Sudanese indigenous chicken (Nm = 4.622).

  3. A new view on dam lines in Polish Arabian horses based on mtDNA analysis.

    PubMed

    Głazewska, Iwona; Wysocka, Anna; Gralak, Barbara; Sell, Jerzy

    2007-01-01

    Polish Arabian horses are one of the oldest and the most important Arab populations in the world. The Polish Arabian Stud Book and the Genealogical Charts by Skorkowski are the main sources of information on the ancestors of Polish Arabs. Both publications were viewed as credible sources of information until the 1990s when the data regarding one of the dam lines was questioned. The aim of the current study was to check the accuracy of the pedigree data of Polish dam lines using mtDNA analysis. The analyses of a 458 bp mtDNA D-loop fragment from representatives of 15 Polish Arabian dam lines revealed 14 distinct haplotypes. The results were inconsistent with pedigree data in the case of two lines. A detailed analysis of the historical sources was performed to explain these discrepancies. Our study revealed that representatives of different lines shared the same haplotypes. We also noted a genetic identity between some lines founded by Polish mares of unknown origin and lines established by desert-bred mares.

  4. Phylogeography of pipistrelle-like bats within the Canary Islands, based on mtDNA sequences.

    PubMed

    Pestano, J; Brown, R P; Suárez, N M; Fajardo, S

    2003-01-01

    Evolution of three Canary Island Vespertilionid bat species, Pipistrellus kuhlii, Pipistrellus maderensis, and Hypsugo savii was studied by comparison of approximately 1 kbp of mtDNA (from cytochrome b and 16S rRNA genes) between islands. mtDNA reveals that both P. kuhlii and P. maderensis exist in sympatry on Tenerife (and possibly other islands). Their morphological similarity explains why their co-occurrence had not been detected previously. Levels of sequence divergence are quite low within P. maderensis. Haplotypes were either identical or separated by /=12 mutational steps) indicating colonization of the latter from the former sometime during the last approximately 1.2 Ma, with low subsequent gene flow. Unlike P. maderensis the El Hierro population alone appears to represent an ESU. The H. savii haplotypes detected in Gran Canaria and Tenerife are identical or separated by 1 mutational step.

  5. Depression-like episodes in mice harboring mtDNA deletions in paraventricular thalamus.

    PubMed

    Kasahara, T; Takata, A; Kato, T M; Kubota-Sakashita, M; Sawada, T; Kakita, A; Mizukami, H; Kaneda, D; Ozawa, K; Kato, T

    2016-01-01

    Depression is a common debilitating human disease whose etiology has defied decades of research. A critical bottleneck is the difficulty in modeling depressive episodes in animals. Here, we show that a transgenic mouse with chronic forebrain expression of a dominant negative mutant of Polg1, a mitochondrial DNA (mtDNA) polymerase, exhibits lethargic behavioral changes, which are associated with emotional, vegetative and psychomotor disturbances, and response to antidepression drug treatment. The results suggested a symptomatic similarity between the lethargic behavioral change that was recurrently and spontaneously experienced by the mutant mice and major depressive episode as defined by DSM-5. A comprehensive screen of mutant brain revealed a hotspot for mtDNA deletions and mitochondrial dysfunction in the paraventricular thalamic nucleus (PVT) with similar defects observed in postmortem brains of patients with mitochondrial disease with mood symptoms. Remarkably, the genetic inhibition of PVT synaptic output by Cre-loxP-dependent expression of tetanus toxin triggered de novo depression-like episodes. These findings identify a novel preclinical mouse model and brain area for major depressive episodes with mitochondrial dysfunction as its cellular mechanism.

  6. Do the Four Clades of the mtDNA Haplogroup L2 Evolve at Different Rates?

    PubMed Central

    Torroni, Antonio; Rengo, Chiara; Guida, Valentina; Cruciani, Fulvio; Sellitto, Daniele; Coppa, Alfredo; Calderon, Fernando Luna; Simionati, Barbara; Valle, Giorgio; Richards, Martin; Macaulay, Vincent; Scozzari, Rosaria

    2001-01-01

    Forty-seven mtDNAs collected in the Dominican Republic and belonging to the African-specific haplogroup L2 were studied by high-resolution RFLP and control-region sequence analyses. Four sets of diagnostic markers that subdivide L2 into four clades (L2a–L2d) were identified, and a survey of published African data sets appears to indicate that these clades encompass all L2 mtDNAs and harbor very different geographic/ethnic distributions. One mtDNA from each of the four clades was completely sequenced by means of a new sequencing protocol that minimizes time and expense. The phylogeny of the L2 complete sequences showed that the two mtDNAs from L2b and L2d seem disproportionately derived, compared with those from L2a and L2c. This result is not consistent with a simple model of neutral evolution with a uniform molecular clock. The pattern of nonsynonymous versus synonymous substitutions hints at a role for selection in the evolution of human mtDNA. Regardless of whether selection is shaping the evolution of modern human mtDNAs, the population screening of L2 mtDNAs for the mutations identified by our complete sequence study should allow the identification of marker motifs of younger age with more restricted geographic distributions, thus providing new clues about African prehistory and the origin and relationships of African ethnic groups. PMID:11595973

  7. An autosomal locus predisposing to multiple deletions of mtDNA on chromosome 3p

    SciTech Connect

    Kaukonen, J.A.; Suomalainen, A.; Peltonen, L.; Amati, P.; Zeviani, M.

    1996-04-01

    Autosomal dominant progressive external ophthalmoplegia (adPEO) is a disorder characterized by ptosis, progressive weakness of the external eye muscles, and general muscle weakness. The patients have multiple deletions of mtDNA on Southern blots or in PCR analysis of muscle DNA and a mild deficiency of one or more respiratory-chain enzymes carrying mtDNA-encoded subunits. The pattern of inheritance indicates a nuclear gene defect predisposing to secondary mtDNA deletions. Recently, in one Finnish family, we assigned an adPEO locus to chromosome 10q23.3-24.3 but also excluded linkage to this same locus in two Italian adPEO families with a phenotype closely resembling the Finnish one. We applied a random mapping approach to informative non-10q-linked Italian families to assign the second locus for adPEO and found strong evidence for linkage on chromosome 3p14.1-21.2 in three Italian families, with a maximum two-point lod score of 4.62 at a recombination fraction of .0. However, in three additional families, linkage to the same chromosomal region was clearly absent, indicating further genetic complexity of the adPEO trait. 19 refs., 3 figs., 2 tabs.

  8. mtDNA analysis reveals a major late Paleolithic population expansion from southwestern to northeastern Europe.

    PubMed Central

    Torroni, A; Bandelt, H J; D'Urbano, L; Lahermo, P; Moral, P; Sellitto, D; Rengo, C; Forster, P; Savontaus, M L; Bonné-Tamir, B; Scozzari, R

    1998-01-01

    mtDNA sequence variation was studied in 419 individuals from nine Eurasian populations, by high-resolution RFLP analysis, and it was followed by sequencing of the control region of a subset of these mtDNAs and a detailed survey of previously published data from numerous other European populations. This analysis revealed that a major Paleolithic population expansion from the "Atlantic zone" (southwestern Europe) occurred 10,000-15,000 years ago, after the Last Glacial Maximum. As an mtDNA marker for this expansion we identified haplogroup V, an autochthonous European haplogroup, which most likely originated in the northern Iberian peninsula or southwestern France at about the time of the Younger Dryas. Its sister haplogroup, H, which is distributed throughout the entire range of Caucasoid populations and which originated in the Near East approximately 25,000-30,000 years ago, also took part in this expansion, thus rendering it by far the most frequent (40%-60%) haplogroup in western Europe. Subsequent migrations after the Younger Dryas eventually carried those "Atlantic" mtDNAs into central and northern Europe. This scenario, already implied by archaeological records, is given overwhelming support from both the distribution of the autochthonous European Y chromosome type 15, as detected by the probes 49a/f, and the synthetic maps of nuclear data. PMID:9545392

  9. mtDNA Affinities of the Peoples of North-Central Mexico

    PubMed Central

    Green, Lance D.; Derr, James N.; Knight, Alec

    2000-01-01

    mtDNA haplotypes of representatives of the cosmopolitan peoples of north-central Mexico were studied. Two hundred twenty-three samples from individuals residing in vicinities of two localities in north-central Mexico were analyzed. A combination of strategies was employed to identify the origin of each haplotype, including length variation analysis of the COII and tRNALYS intergenic region, nucleotide sequence analysis of control region hypervariable segment 1, and RFLP analysis of PCR products spanning diagnostic sites. Analysis of these data revealed that the majority of the mtDNA haplotypes were of Native American origin, belonging to one of four primary Native American haplogroups. Others were of European or African origin, and the frequency of African haplotypes was equivalent to that of haplotypes of European derivation. These results provide diagnostic, discrete character, molecular genetic evidence that, together with results of previous studies of classical genetic systems, is informative with regard to both the magnitude of African admixture and the relative maternal contribution of African, European, and Native American peoples to the genetic heritage of Mexico. Phylogenetic analysis revealed that African sequences formed a basal, paraphyletic group. PMID:10712213

  10. Comparative mtDNA analyses of three sympatric macropodids from a conservation area on the Huon Peninsula, Papua New Guinea.

    PubMed

    McGreevy, Thomas J; Dabek, Lisa; Husband, Thomas P

    2016-07-01

    Matschie's tree kangaroo (Dendrolagus matschiei), New Guinea pademelon (Thylogale browni), and small dorcopsis (Dorcopsulus vanheurni) are sympatric macropodid taxa, of conservation concern, that inhabit the Yopno-Urawa-Som (YUS) Conservation Area on the Huon Peninsula, Papua New Guinea. We sequenced three partial mitochondrial DNA (mtDNA) genes from the three taxa to (i) investigate network structure; and (ii) identify conservation units within the YUS Conservation Area. All three taxa displayed a similar pattern in the spatial distribution of their mtDNA haplotypes and the Urawa and Som rivers on the Huon may have acted as a barrier to maternal gene flow. Matschie's tree kangaroo and New Guinea pademelon within the YUS Conservation Area should be managed as single conservation units because mtDNA nucleotides were not fixed for a given geographic area. However, two distinct conservation units were identified for small dorcopsis from the two different mountain ranges within the YUS Conservation Area.

  11. Respiratory function in cybrid cell lines carrying European mtDNA haplogroups: implications for Leber's hereditary optic neuropathy.

    PubMed

    Carelli, Valerio; Vergani, Lodovica; Bernazzi, Barbara; Zampieron, Claudia; Bucchi, Laura; Valentino, Maria; Rengo, Chiara; Torroni, Antonio; Martinuzzi, Andrea

    2002-10-09

    The possibility that some combinations of mtDNA polymorphisms, previously associated with Leber's hereditary optic neuropathy (LHON), may affect mitochondrial respiratory function was tested in osteosarcoma-derived transmitochondrial cytoplasmic hybrids (cybrids). In this cellular system, in the presence of the same nuclear background, different exogenous mtDNAs are used to repopulate a parental cell line previously devoid of its original mtDNA. No detectable differences in multiple parameters exploring respiratory function were observed when mtDNAs belonging to European haplogroups X, H, T and J were used. Different possible explanations for the previously established association between haplogroup J and LHON 11778/ND4 and 14484/ND6 pathogenic mutations are discussed, including the unconventional proposal that mtDNA haplogroup J may exert a protective rather than detrimental effect.

  12. Differences in mtDNA haplogroup distribution among 3 Jewish populations alter susceptibility to T2DM complications

    PubMed Central

    Feder, Jeanette; Blech, Ilana; Ovadia, Ofer; Amar, Shirly; Wainstein, Julio; Raz, Itamar; Dadon, Sarah; Arking, Dan E; Glaser, Benjamin; Mishmar, Dan

    2008-01-01

    Background Recent genome-wide association studies searching for candidate susceptibility loci for common complex diseases such as type 2 diabetes mellitus (T2DM) and its common complications have uncovered novel disease-associated genes. Nevertheless these large-scale population screens often overlook the tremendous variation in the mitochondrial genome (mtDNA) and its involvement in complex disorders. Results We have analyzed the mitochondrial DNA (mtDNA) genetic variability in Ashkenazi (Ash), Sephardic (Seph) and North African (NAF) Jewish populations (total n = 1179). Our analysis showed significant differences (p < 0.001) in the distribution of mtDNA genetic backgrounds (haplogroups) among the studied populations. To test whether these differences alter the pattern of disease susceptibility, we have screened our three Jewish populations for an association of mtDNA genetic haplogroups with T2DM complications. Our results identified population-specific susceptibility factors of which the best example is the Ashkenazi Jewish specific haplogroup N1b1, having an apparent protective effect against T2DM complications in Ash (p = 0.006), being absent in the NAF population and under-represented in the Seph population. We have generated and analyzed whole mtDNA sequences from the disease associated haplogroups revealing mutations in highly conserved positions that are good candidates to explain the phenotypic effect of these genetic backgrounds. Conclusion Our findings support the possibility that recent bottleneck events leading to over-representation of minor mtDNA alleles in specific genetic isolates, could result in population-specific susceptibility loci to complex disorders. PMID:18445251

  13. Collated mutations in mitochondrial DNA (mtDNA) depletion syndrome (excluding the mitochondrial gamma polymerase, POLG1).

    PubMed

    Poulton, J; Hirano, M; Spinazzola, A; Arenas Hernandez, M; Jardel, C; Lombès, A; Czermin, B; Horvath, R; Taanman, J W; Rotig, A; Zeviani, M; Fratter, C

    2009-12-01

    These tables list both published and a number of unpublished mutations in genes associated with early onset defects in mitochondrial DNA (mtDNA) maintenance including C10orf2, SUCLG1, SUCLA2, TYMP, RRM2B, MPV17, DGUOK and TK2. The list should not be taken as evidence that any particular mutation is pathogenic. We have included genes known to cause mtDNA depletion, excluding POLG1, because of the existing database (http://tools.niehs.nih.gov/polg/). We have also excluded mutations in C10orf2 associated with dominant adult onset disorders.

  14. MtDNA haplogroup analysis of black Brazilian and sub-Saharan populations: implications for the Atlantic slave trade.

    PubMed

    Silva, Wilson Araújo; Bortolini, Maria Cátira; Schneider, Maria Paula Cruz; Marrero, Andrea; Elion, Jacques; Krishnamoorthy, Rajagopal; Zago, Marco Antonio

    2006-02-01

    Seventy individuals from two African and four black Brazilian populations were studied for the first hypervariable segment of mtDNA. To delineate a more complete phylogeographic scenario of the African mtDNA haplogroups in Brazil and to provide additional information on the nature of the Atlantic slave trade, we analyzed our data together with previously published data. The results indicate different sources of African slaves for the four major Brazilian regions. In addition, the data revealed patterns that differ from those expected on the basis of historical registers, thus suggesting the role of ethnic sex differences in the slave trade.

  15. Variability of the honey bee mite Varroa destructor in Serbia, based on mtDNA analysis.

    PubMed

    Gajic, Bojan; Radulovic, Zeljko; Stevanovic, Jevrosima; Kulisic, Zoran; Vucicevic, Milos; Simeunovic, Predrag; Stanimirovic, Zoran

    2013-09-01

    Only two mitochondrial haplotypes (Korea and Japan) of Varroa destructor, the ectoparasitic honey bee mite, are known to be capable of infesting and successfully reproducing in Apis mellifera colonies worldwide. Varroa destructor (then called Varroa jacobsoni) was observed in Serbia for the first time in 1976. In order to obtain insight into the genetic variability of the mites parasitizing A. mellifera we analyzed 45 adult female mites sampled from nine localities dispersed throughout Serbia. Four fragments within cox1, atp6, cox3 and cytb mtDNA genes were sequenced. The Korea haplotype of V. destructor was found to be present at all localities, but also two new haplotypes (Serbia 1 and Peshter 1) were revealed, based on cox1 and cytb sequence variability. The simultaneous occurrence of Korea and Serbia 1 haplotypes was observed at five localities, whereas Peshter 1 haplotype was identifed at only one place.

  16. MtDNA analysis of global populations support that major population expansions began before Neolithic Time

    NASA Astrophysics Data System (ADS)

    Zheng, Hong-Xiang; Yan, Shi; Qin, Zhen-Dong; Jin, Li

    2012-10-01

    Agriculture resulted in extensive population growths and human activities. However, whether major human expansions started after Neolithic Time still remained controversial. With the benefit of 1000 Genome Project, we were able to analyze a total of 910 samples from 11 populations in Africa, Europe and Americas. From these random samples, we identified the expansion lineages and reconstructed the historical demographic variations. In all the three continents, we found that most major lineage expansions (11 out of 15 star lineages in Africa, all autochthonous lineages in Europe and America) coalesced before the first appearance of agriculture. Furthermore, major population expansions were estimated after Last Glacial Maximum but before Neolithic Time, also corresponding to the result of major lineage expansions. Considering results in current and previous study, global mtDNA evidence showed that rising temperature after Last Glacial Maximum offered amiable environments and might be the most important factor for prehistorical human expansions.

  17. MtDNA polymorphism in the Hungarians: comparison to three other Finno-Ugric-speaking populations.

    PubMed

    Lahermo, P; Laitinen, V; Sistonen, P; Béres, J; Karcagi, V; Savontaus, M L

    2000-01-01

    Mitochondrial DNA sequence variation as well as restriction site polymorphisms were examined in 437 individuals from four Finno-Ugric-speaking populations. These included the Hungarians (Budapest region and the Csángós from Hungary and Romania), the Finns and two Saami groups from northeastern Finland (Inari Saami and Skolt Saami), and the Erzas from central Russia. The mtDNA data obtained in this study were combined with our previous data on Y chromosomal variation for eight different loci in these populations. The genetic variation observed among the Hungarians resembled closely that found in other European populations. The Hungarians could not be distinguished from the neighboring populations (e.g., the Austrians) any more than from their Finno-Ugric linguistic relatives.

  18. MtDNA metagenomics reveals large-scale invasion of belowground arthropod communities by introduced species.

    PubMed

    Cicconardi, Francesco; Borges, Paulo A V; Strasberg, Dominique; Oromí, Pedro; López, Heriberto; Pérez-Delgado, Antonio J; Casquet, Juliane; Caujapé-Castells, Juli; Fernández-Palacios, José María; Thébaud, Christophe; Emerson, Brent C

    2017-01-31

    Using a series of standardized sampling plots within forest ecosystems in remote oceanic islands, we reveal fundamental differences between the structuring of aboveground and belowground arthropod biodiversity that are likely due to large-scale species introductions by humans. Species of beetle and spider were sampled almost exclusively from single islands, while soil-dwelling Collembola exhibited more than tenfold higher species sharing among islands. Comparison of Collembola mitochondrial metagenomic data to a database of more than 80 000 Collembola barcode sequences revealed almost 30% of sampled island species are genetically identical, or near identical, to individuals sampled from often very distant geographic regions of the world. Patterns of mtDNA relatedness among Collembola implicate human-mediated species introductions, with minimum estimates for the proportion of introduced species on the sampled islands ranging from 45% to 88%. Our results call for more attention to soil mesofauna to understand the global extent and ecological consequences of species introductions.

  19. [PCR-RFLP analysis of the mtDNA Cytb gene in three different horse breeds].

    PubMed

    Li, Jin-Lian; Shi, You-Fei; Bu, Ren-Qiqige; Mang, Lai

    2006-08-01

    Restriction endonucleases, namely BamH I, Taq I, Hae III, Rsa I and Hinc II, were used to analyze the polymorphism of partial mtDNA Cytb gene sequences from 256 horses 6 types (Thoroughbred, Sanhe, Wuzhumuqin, Xinihe, Wushen and Pony) including the imported breed, cultivated breed and local breed. The products of endonuclease digestion were run on 8% non-denaturing polyacrylamide gel electrophoresis and detected by silver staining. Results indicated BamH I and Taq I polymorphism. In all 7 restriction patterns were defected that could be sorted into 3 haplotypes, of which haplotypes I and III were the basic haplotypes. We infer that these horses came from one female ancestor through the analysis thorough one pattern, namely BamH I-B.

  20. Polymorphisms of mtDNA control region in Tunisian and Moroccan populations: an enrichment of forensic mtDNA databases with Northern Africa data.

    PubMed

    Turchi, Chiara; Buscemi, Loredana; Giacchino, Erika; Onofri, Valerio; Fendt, Liane; Parson, Walther; Tagliabracci, Adriano

    2009-06-01

    Current forensic mitochondrial (mt)DNA databases are limited in representative population data of African origin. We investigated HVS-I/HVS-II sequences of 120 Tunisian and Moroccan healthy male donors applying stringent quality criteria to assure high quality of the data and phylogenetic alignment and notation of the sequences. Among 64 Tunisians, 56 different haplotypes were observed and the most common haplotype (16187T 16189C 16223T 16264T 16270T 16278T 16293G 16311C 73G 152C 182T 185T 195C 247A 263G 309.1C 315.1C; haplogroup (hg) L1b) was shared by four individuals. 56 Moroccans could be assigned to 52 different haplotypes where the most common haplotype was of West Eurasian origin with the hg H sequence motif 263G 315.1C and variations in the HVS-II polyC-stretch (309.1C 309.2C) shared by six samples. The majority of the observed haplotypes belong to the west Eurasian phylogeny (50% in Tunisians and 62.5% in Moroccans). Our data are consistent with the current phylogeographic knowledge displaying the occurrence of sub-Saharan haplogroup L sequences, found in 48.4% of Tunisians and 25% of Moroccans as well as the presence of the two re-migrated haplogroups U6 (7.8% and 1.8% in Tunisians and Moroccans, respectively) and M1 (1.6% in Tunisians and 8.9% in Moroccans).

  1. Maternal inheritance of mitochondrial DNA (mtDNA) in the Pacific oyster (Crassostrea gigas): a preliminary study using mtDNA sequence analysis with evidence of random distribution of MitoTracker-stained sperm mitochondria in fertilized eggs.

    PubMed

    Obata, Mayu; Shimizu, Michiyo; Sano, Natsumi; Komaru, Akira

    2008-03-01

    In many bivalve species, paternal and maternal mitochondrial DNA (mtDNA) from sperm and eggs is transmitted to the offspring. This phenomenon is known as doubly uniparental inheritance (DUI). In these species, sperm mtDNA (M type) is inherited by the male gonad of the offspring. Egg mtDNA (F type) is inherited by both male and female somatic cells and female gonadal cells. In Mytilidae, sperm mitochondria are distributed in the cytoplasm of differentiating male germ cells because they are transmitted to the male gonad. In the present study, we investigated maternal inheritance of mtDNA in the Pacific oyster, Crassostrea gigas. Sequence analysis of two mitochondrial non-coding regions revealed an identical sequence pattern in the gametes and adductor muscle samples taken from six males and five females. To observe whether sperm mitochondria were specifically located in the cytoplasm of differentiating germ cells, their distribution was recorded in C. gigas fertilized eggs by vital staining with MitoTracker Green. Although the 1D blastomere was identified in the cytoplasm of differentiating germ cells, sperm mitochondria were located at the 1D blastomere in only 32% of eggs during the 8-cell stage. Thus, in C. gigas, sperm mitochondria do not specifically locate in the germ cell region at the 1D blastomere. We suggest that the distribution of sperm mitochondria is not associated with germ cell formation in C. gigas. Furthermore, as evidenced by the mtDNA sequences of two non-coding regions, we conclude that mitochondrial DNA is maternally inherited in this species.

  2. HVSI polymorphism indicates multiple origins of mtDNA in the Hazarewal population of Northern Pakistan.

    PubMed

    Akbar, N; Ahmad, H; Nadeem, M S; Hemphill, B E; Muhammad, K; Ahmad, W; Ilyas, M

    2016-06-24

    Mitochondrial DNA (mtDNA) is an important tool used to explore ethnogenetics and the evolutionary history of human populations. In this study, hypervariable segment I (HVSI) from mtDNA was analyzed to establish the genetic lineage of the Hazarewal populations residing in the Mansehra and Abbottabad districts of Northern Pakistan. HVSI was extracted from genetic specimens obtained from 225 unrelated male and female individuals belonging to seven distinct Pakistani ethnic groups (31 Abbassis, 44 Awans, 38 Gujars, 16 Jadoons, 23 Karlals, 33 Syeds, and 40 Tanolis). Eighty-three haplogroups, 39 of which were unique, were identified; haplogroup H was predominantly represented (in 40% of the people), followed by haplogroups M (21.78%), R (16.89%), N (15.56%), L (3.11%), and HV (2.67%). The results revealed a sex-biased genetic contribution from putative West Eurasian, South Asian, and Sub-Saharan populations to the genetic lineage of Hazarewal ancestry, with the effect of Eurasians being predominant. The HVSI nucleotide sequences exhibited some characteristic deletion mutations between 16,022 and 16,193 bp, which is characteristic of specific ethnic groups. HVSI sequence homology showed that Hazarewal populations fall into three major clusters: Syeds and Awans sorted out into cluster I; Tanolis, Gujars, and Karlals segregated in cluster II; and Abbassis and Jadoons in cluster III. Here, we have reported the firsthand genetic information and evolutionary sketch of the selected populations residing alongside the historical Silk Route, which provides a baseline for collating the origin, route of migration, and phylogenetics of the population.

  3. A Signal, from Human mtDNA, of Postglacial Recolonization in Europe

    PubMed Central

    Torroni, Antonio; Bandelt, Hans-Jürgen; Macaulay, Vincent; Richards, Martin; Cruciani, Fulvio; Rengo, Chiara; Martinez-Cabrera, Vicente; Villems, Richard; Kivisild, Toomas; Metspalu, Ene; Parik, Jüri; Tolk, Helle-Viivi; Tambets, Kristiina; Forster, Peter; Karger, Bernd; Francalacci, Paolo; Rudan, Pavao; Janicijevic, Branka; Rickards, Olga; Savontaus, Marja-Liisa; Huoponen, Kirsi; Laitinen, Virpi; Koivumäki, Satu; Sykes, Bryan; Hickey, Eileen; Novelletto, Andrea; Moral, Pedro; Sellitto, Daniele; Coppa, Alfredo; Al-Zaheri, Nadia; Santachiara-Benerecetti, A. Silvana; Semino, Ornella; Scozzari, Rosaria

    2001-01-01

    Mitochondrial HVS-I sequences from 10,365 subjects belonging to 56 populations/geographical regions of western Eurasia and northern Africa were first surveyed for the presence of the T→C transition at nucleotide position 16298, a mutation which has previously been shown to characterize haplogroup V mtDNAs. All mtDNAs with this mutation were then screened for a number of diagnostic RFLP sites, revealing two major subsets of mtDNAs. One is haplogroup V proper, and the other has been termed “pre*V,” since it predates V phylogenetically. The rather uncommon pre*V tends to be scattered throughout Europe (and northwestern Africa), whereas V attains two peaks of frequency: one situated in southwestern Europe and one in the Saami of northern Scandinavia. Geographical distributions and ages support the scenario that pre*V originated in Europe before the Last Glacial Maximum (LGM), whereas the more recently derived haplogroup V arose in a southwestern European refugium soon after the LGM. The arrival of V in eastern/central Europe, however, occurred much later, possibly with (post-)Neolithic contacts. The distribution of haplogroup V mtDNAs in modern European populations would thus, at least in part, reflect the pattern of postglacial human recolonization from that refugium, affecting even the Saami. Overall, the present study shows that the dissection of mtDNA variation into small and well-defined evolutionary units is an essential step in the identification of spatial frequency patterns. Mass screening of a few markers identified using complete mtDNA sequences promises to be an efficient strategy for inferring features of human prehistory. PMID:11517423

  4. MtDNA diversity of Ghana: a forensic and phylogeographic view

    PubMed Central

    Fendt, Liane; Röck, Alexander; Zimmermann, Bettina; Bodner, Martin; Thye, Thorsten; Tschentscher, Frank; Owusu-Dabo, Ellis; Göbel, Tanja M.K.; Schneider, Peter M.; Parson, Walther

    2012-01-01

    West Africa is characterized by a migration history spanning more than 150,000 years. Climate changes but also political circumstances were responsible for several early but also recent population movements that shaped the West African mitochondrial landscape. The aim of the study was to establish a Ghanaian mtDNA dataset for forensic purposes and to investigate the diversity of the Ghanaian population sample with respect to surrounding populations. We sequenced full mitochondrial control regions of 193 Akan people from Ghana and excluded two apparently close maternally related individuals due to preceding kinship testing. The remaining dataset comprising 191 sequences was applied as etalon for quasi-median network analysis and was subsequently combined with 99 additional control region sequences from surrounding West African countries. All sequences were incorporated into the EMPOP database enriching the severely underrepresented African mtDNA pool. For phylogeographic considerations, the Ghanaian haplotypes were compared to those of 19 neighboring populations comprising a total number of 6198 HVS1 haplotypes. We found extensive genetic admixture between the Ghanaian lineages and those from adjacent populations diminishing with geographical distance. The extent of genetic admixture reflects the long but also recent history of migration waves within West Africa mainly caused by changing environmental conditions. Also, evidence for potential socio-economical influences such as trade routes is provided by the occurrence of U6b and U6d sequences found in Dubai but also in Tunisia leading to the African West Coast via Mauritania and Senegal but also via Niger, Nigeria to Cameroon. PMID:21723214

  5. Ancient substructure in early mtDNA lineages of southern Africa.

    PubMed

    Barbieri, Chiara; Vicente, Mário; Rocha, Jorge; Mpoloka, Sununguko W; Stoneking, Mark; Pakendorf, Brigitte

    2013-02-07

    Among the deepest-rooting clades in the human mitochondrial DNA (mtDNA) phylogeny are the haplogroups defined as L0d and L0k, which are found primarily in southern Africa. These lineages are typically present at high frequency in the so-called Khoisan populations of hunter-gatherers and herders who speak non-Bantu languages, and the early divergence of these lineages led to the hypothesis of ancient genetic substructure in Africa. Here we update the phylogeny of the basal haplogroups L0d and L0k with 500 full mtDNA genome sequences from 45 southern African Khoisan and Bantu-speaking populations. We find previously unreported subhaplogroups and greatly extend the amount of variation and time-depth of most of the known subhaplogroups. Our major finding is the definition of two ancient sublineages of L0k (L0k1b and L0k2) that are present almost exclusively in Bantu-speaking populations from Zambia; the presence of such relic haplogroups in Bantu speakers is most probably due to contact with ancestral pre-Bantu populations that harbored different lineages than those found in extant Khoisan. We suggest that although these populations went extinct after the immigration of the Bantu-speaking populations, some traces of their haplogroup composition survived through incorporation into the gene pool of the immigrants. Our findings thus provide evidence for deep genetic substructure in southern Africa prior to the Bantu expansion that is not represented in extant Khoisan populations.

  6. A melting pot of multicontinental mtDNA lineages in admixed Venezuelans.

    PubMed

    Gómez-Carballa, Alberto; Ignacio-Veiga, Ana; Alvarez-Iglesias, Vanesa; Pastoriza-Mourelle, Ana; Ruíz, Yarimar; Pineda, Lennie; Carracedo, Angel; Salas, Antonio

    2012-01-01

    The arrival of Europeans in Colonial and post-Colonial times coupled with the forced introduction of sub-Saharan Africans have dramatically changed the genetic background of Venezuela. The main aim of the present study was to evaluate, through the study of mitochondrial DNA (mtDNA) variation, the extent of admixture and the characterization of the most likely continental ancestral sources of present-day urban Venezuelans. We analyzed two admixed populations that have experienced different demographic histories, namely, Caracas (n = 131) and Pueblo Llano (n = 219). The native American component of admixed Venezuelans accounted for 80% (46% haplogroup [hg] A2, 7% hg B2, 21% hg C1, and 6% hg D1) of all mtDNAs; while the sub-Saharan and European contributions made up ∼10% each, indicating that Trans-Atlantic immigrants have only partially erased the native American nature of Venezuelans. A Bayesian-based model allowed the different contributions of European countries to admixed Venezuelans to be disentangled (Spain: ∼38.4%, Portugal: ∼35.5%, Italy: ∼27.0%), in good agreement with the documented history. Seventeen entire mtDNA genomes were sequenced, which allowed five new native American branches to be discovered. B2j and B2k, are supported by two different haplotypes and control region data, and their coalescence ages are 3.9 k.y. (95% C.I. 0-7.8) and 2.6 k.y. (95% C.I. 0.1-5.2), respectively. The other clades were exclusively observed in Pueblo Llano and they show the fingerprint of strong recent genetic drift coupled with severe historical consanguinity episodes that might explain the high prevalence of certain Mendelian and complex multi-factorial diseases in this region.

  7. The Expansion of mtDNA Haplogroup L3 within and out of Africa.

    PubMed

    Soares, Pedro; Alshamali, Farida; Pereira, Joana B; Fernandes, Verónica; Silva, Nuno M; Afonso, Carla; Costa, Marta D; Musilová, Eliska; Macaulay, Vincent; Richards, Martin B; Cerny, Viktor; Pereira, Luísa

    2012-03-01

    Although fossil remains show that anatomically modern humans dispersed out of Africa into the Near East ∼100 to 130 ka, genetic evidence from extant populations has suggested that non-Africans descend primarily from a single successful later migration. Within the human mitochondrial DNA (mtDNA) tree, haplogroup L3 encompasses not only many sub-Saharan Africans but also all ancient non-African lineages, and its age therefore provides an upper bound for the dispersal out of Africa. An analysis of 369 complete African L3 sequences places this maximum at ∼70 ka, virtually ruling out a successful exit before 74 ka, the date of the Toba volcanic supereruption in Sumatra. The similarity of the age of L3 to its two non-African daughter haplogroups, M and N, suggests that the same process was likely responsible for both the L3 expansion in Eastern Africa and the dispersal of a small group of modern humans out of Africa to settle the rest of the world. The timing of the expansion of L3 suggests a link to improved climatic conditions after ∼70 ka in Eastern and Central Africa rather than to symbolically mediated behavior, which evidently arose considerably earlier. The L3 mtDNA pool within Africa suggests a migration from Eastern Africa to Central Africa ∼60 to 35 ka and major migrations in the immediate postglacial again linked to climate. The largest population size increase seen in the L3 data is 3-4 ka in Central Africa, corresponding to Bantu expansions, leading diverse L3 lineages to spread into Eastern and Southern Africa in the last 3-2 ka.

  8. Localized population divergence of vervet monkeys (Chlorocebus spp.) in South Africa: evidence from mtDNA

    PubMed Central

    Turner, Trudy R.; Coetzer, Willem G.; Schmitt, Christopher A.; Lorenz, Joseph G.; Freimer, Nelson B.; Grobler, J. Paul

    2015-01-01

    Objectives Vervet monkeys are common in most tree-rich areas of South Africa, but their absence from grassland and semi-desert areas of the country suggest potentially restricted and mosaic local population patterns that may have relevance to local phenotype patterns and selection. A portion of the mtDNA control region was sequenced to study patterns of genetic differentiation. Materials and Methods DNA was extracted and mtDNA sequences were obtained from 101 vervet monkeys at 15 localities which represent both an extensive (widely across the distribution range) and intensive (more than one troop at most of the localities) sampling strategy. Analyses utilized Arlequin 3.1, MEGA 6, BEAST v1.5.2 and Network V3.6.1 Results The dataset contained 26 distinct haplotypes, with six populations fixed for single haplotypes. Pairwise P-distance among population pairs showed significant differentiation among most population pairs, but with non-significant differences among populations within some regions. Populations were grouped into three broad clusters in a maximum likelihood phylogenetic tree and a haplotype network. These clusters correspond to (i) north-western, northern and north-eastern parts of the distribution range as well as the northern coastal belt; (ii) central areas of the country; and (iii) southern part of the Indian Ocean coastal belt, and adjacent inland areas. Discussion Apparent patterns of genetic structure correspond to current and past distribution of suitable habitat, geographic barriers to gene flow, geographic distance and female philopatry. However, further work on nuclear markers and other genomic data is necessary to confirm these results. PMID:26265297

  9. A signal, from human mtDNA, of postglacial recolonization in Europe.

    PubMed

    Torroni, A; Bandelt, H J; Macaulay, V; Richards, M; Cruciani, F; Rengo, C; Martinez-Cabrera, V; Villems, R; Kivisild, T; Metspalu, E; Parik, J; Tolk, H V; Tambets, K; Forster, P; Karger, B; Francalacci, P; Rudan, P; Janicijevic, B; Rickards, O; Savontaus, M L; Huoponen, K; Laitinen, V; Koivumäki, S; Sykes, B; Hickey, E; Novelletto, A; Moral, P; Sellitto, D; Coppa, A; Al-Zaheri, N; Santachiara-Benerecetti, A S; Semino, O; Scozzari, R

    2001-10-01

    Mitochondrial HVS-I sequences from 10,365 subjects belonging to 56 populations/geographical regions of western Eurasia and northern Africa were first surveyed for the presence of the T-->C transition at nucleotide position 16298, a mutation which has previously been shown to characterize haplogroup V mtDNAs. All mtDNAs with this mutation were then screened for a number of diagnostic RFLP sites, revealing two major subsets of mtDNAs. One is haplogroup V proper, and the other has been termed "pre*V," since it predates V phylogenetically. The rather uncommon pre*V tends to be scattered throughout Europe (and northwestern Africa), whereas V attains two peaks of frequency: one situated in southwestern Europe and one in the Saami of northern Scandinavia. Geographical distributions and ages support the scenario that pre*V originated in Europe before the Last Glacial Maximum (LGM), whereas the more recently derived haplogroup V arose in a southwestern European refugium soon after the LGM. The arrival of V in eastern/central Europe, however, occurred much later, possibly with (post-)Neolithic contacts. The distribution of haplogroup V mtDNAs in modern European populations would thus, at least in part, reflect the pattern of postglacial human recolonization from that refugium, affecting even the Saami. Overall, the present study shows that the dissection of mtDNA variation into small and well-defined evolutionary units is an essential step in the identification of spatial frequency patterns. Mass screening of a few markers identified using complete mtDNA sequences promises to be an efficient strategy for inferring features of human prehistory.

  10. mtDNA diversity in Azara's owl monkeys (Aotus azarai azarai) of the Argentinean Chaco.

    PubMed

    Babb, Paul L; Fernandez-Duque, Eduardo; Baiduc, Caitlin A; Gagneux, Pascal; Evans, Sian; Schurr, Theodore G

    2011-10-01

    Owl monkeys (Aotus spp.) inhabit much of South America yet represent an enigmatic evolutionary branch among primates. While morphological, cytogenetic, and immunological evidence suggest that owl monkey populations have undergone isolation and diversification since their emergence in the New World, problems with adjacent species ranges, and sample provenance have complicated efforts to characterize genetic variation within the genus. As a result, the phylogeographic history of owl monkey species and subspecies remains unclear, and the extent of genetic diversity at the population level is unknown. To explore these issues, we analyzed mitochondrial DNA (mt DNA) variation in a population of wild Azara's owl monkeys (Aotus azarai azarai) living in the Gran Chaco region of Argentina. We sequenced the complete mitochondrial genome from one individual (16,585 base pairs (bp)) and analyzed 1,099 bp of the hypervariable control region (CR) and 696 bp of the cytochrome oxidase II (COII) gene in 117 others. In addition, we sequenced the mitochondrial genome (16,472 bp) of one Nancy Ma's owl monkey (A. nancymaae). Based on the whole mtDNA and COII data, we observed an ancient phylogeographic discontinuity among Aotus species living north, south, and west of the Amazon River that began more than eight million years ago. Our population analyses identified three major CR lineages and detected a high level of haplotypic diversity within A. a. azarai. These data point to a recent expansion of Azara's owl monkeys into the Argentinean Chaco. Overall, we provide a detailed view of owl monkey mtDNA variation at genus, species, and population levels.

  11. Maternal admixture and population structure in Mexican-Mestizos based on mtDNA haplogroups.

    PubMed

    Martínez-Cortés, Gabriela; Salazar-Flores, Joel; Haro-Guerrero, Javier; Rubi-Castellanos, Rodrigo; Velarde-Félix, Jésus S; Muñoz-Valle, José F; López-Casamichana, Mavil; Carrillo-Tapia, Eduardo; Canseco-Avila, Luis M; Bravi, Claudio M; López-Armenta, Mauro; Rangel-Villalobos, Héctor

    2013-08-01

    The maternal ancestry (mtDNA) has important applications in different research fields, such as evolution, epidemiology, identification, and human population history. This is particularly interesting in Mestizos, which constitute the main population in Mexico (∼93%) resulting from post-Columbian admixture between Spaniards, Amerindians, and African slaves, principally. Consequently, we conducted minisequencing analysis (SNaPshot) of 11 mitochondrial single-nucleotide polymorphisms in 742 Mestizos of 10 populations from different regions in Mexico. The predominant maternal ancestry was Native American (92.9%), including Haplogroups A, B, C, and D (47, 23.7, 15.9, and 6.2%, respectively). Conversely, European and African ancestries were less frequent (5.3 and 1.9%, respectively). The main characteristics of the maternal lineages observed in Mexican-Mestizos comprised the following: 1) contrasting geographic gradient of Haplogroups A and C; 2) increase of European lineages toward the Northwest; 3) low or absent, but homogeneous, African ancestry throughout the Mexican territory; 4) maternal lineages in Mestizos roughly represent the genetic makeup of the surrounding Amerindian groups, particularly toward the Southeast, but not in the North and West; 5) continuity over time of the geographic distribution of Amerindian lineages in Mayas; and 6) low but significant maternal population structure (FST  = 2.8%; P = 0.0000). The average ancestry obtained from uniparental systems (mtDNA and Y-chromosome) in Mexican-Mestizos was correlated with previous ancestry estimates based on autosomal systems (genome-wide single-nucleotide polymorphisms and short tandem repeats). Finally, the comparison of paternal and maternal lineages provided additional information concerning the gender bias admixture, mating patterns, and population structure in Mestizos throughout the Mexican territory.

  12. Origins and dispersals of Pacific peoples: Evidence from mtDNA phylogenies of the Pacific rat

    PubMed Central

    Matisoo-Smith, E.; Robins, J. H.

    2004-01-01

    The human settlement of the Pacific in general, and the origin of the Polynesians in particular, have been topics of debate for over two centuries. Polynesian origins are most immediately traced to people who arrived in the Fiji, Tonga, and Samoa region ≈3,000 B.P. and are clearly associated with the Lapita Cultural Complex. Although this scenario of the immediate origins of the Polynesians is generally accepted, the debate on the ultimate origin of the Polynesians and the Lapita cultural complex continues. Our previous research has shown that analyses of mtDNA variation in the Pacific rat (Rattus exulans), often transported as a food item in the colonizing canoes, are valuable for tracing prehistoric human migration within Polynesia. Here we present mtDNA phylogenies based on ≈240 base pairs of the d-loop from both archaeological and modern samples collected from Island Southeast Asia and the Pacific. We identify three major haplogroups, two of which occur in the Pacific. Comparing our results with Lapita models of Oceanic settlement, we are able to reject two often cited but simplistic models, finding support instead for multifaceted models incorporating a more complex view of the Lapita intrusion. This study is unique and valuable in that R. exulans is the only organism associated with the Lapita dispersal for which there are sufficient ancient and extant populations available for genetic analysis. By tracking population changes through time, we can understand more fully the settlement process and population interactions in both Near and Remote Oceania. PMID:15184658

  13. Paternal transmission of mitochondrial DNA as an integral part of mitochondrial inheritance in metapopulations of Drosophila simulans.

    PubMed

    Wolff, J N; Nafisinia, M; Sutovsky, P; Ballard, J W O

    2013-01-01

    Maternal inheritance is one of the hallmarks of animal mitochondrial DNA (mtDNA) and central to its success as a molecular marker. This mode of inheritance and subsequent lack of heterologous recombination allows us to retrace evolutionary relationships unambiguously down the matriline and without the confounding effects of recombinant genetic information. Accumulating evidence of biparental inheritance of mtDNA (paternal leakage), however, challenges our current understanding of how this molecule is inherited. Here, using Drosophila simulans collected from an East African metapopulation exhibiting recurring mitochondrial heteroplasmy, we conducted single fly matings and screened F1 offspring for the presence of paternal mtDNA using allele-specific PCR assays (AS-PCR). In all, 27 out of 4092 offspring were identified as harboring paternal mtDNA, suggesting a frequency of 0.66% paternal leakage in this species. Our findings strongly suggest that recurring mtDNA heteroplasmy as observed in natural populations of Drosophila simulans is most likely caused by repeated paternal leakage. Our findings further suggest that this phenomenon to potentially be an integral part of mtDNA inheritance in these populations and consequently of significance for mtDNA as a molecular marker.

  14. Targeting the mitochondrial genome via a dual function MITO-Porter: evaluation of mtDNA levels and mitochondrial function.

    PubMed

    Yamada, Yuma; Harashima, Hideyoshi

    2015-01-01

    Genetic mutations and defects in mitochondrial DNA (mtDNA) are associated with certain types of mitochondrial dysfunction, ultimately resulting in the occurrence of a variety of human diseases. For an effective mitochondrial gene therapy, it will be necessary to deliver therapeutic agents to the innermost mitochondrial space (the mitochondrial matrix), which contains the mtDNA pool. We recently developed a MITO-Porter, a liposome-based nano-carrier that delivers cargo to mitochondria via a membrane-fusion mechanism. Using propidium iodide, as a probe to detect mtDNA, we were able to confirm that the MITO-Porter delivered cargoes to mitochondrial matrices in living cells. More recently, we constructed a Dual Function (DF)-MITO-Porter, a liposome-based nanocarrier for mitochondrial delivery via a stepwise process. In this chapter, we describe the methodology used to deliver bioactive molecules to the mitochondrial matrix using the above DF-MITO-Porter, and the evaluation of mtDNA levels and mitochondrial activities in living cells.

  15. Mitochondrial DNA ligase is dispensable for the viability of cultured cells but essential for mtDNA maintenance.

    PubMed

    Shokolenko, Inna N; Fayzulin, Rafik Z; Katyal, Sachin; McKinnon, Peter J; Wilson, Glenn L; Alexeyev, Mikhail F

    2013-09-13

    Multiple lines of evidence support the notion that DNA ligase III (LIG3), the only DNA ligase found in mitochondria, is essential for viability in both whole organisms and in cultured cells. Previous attempts to generate cells devoid of mitochondrial DNA ligase failed. Here, we report, for the first time, the derivation of viable LIG3-deficient mouse embryonic fibroblasts. These cells lack mtDNA and are auxotrophic for uridine and pyruvate, which may explain the apparent lethality of the Lig3 knock-out observed in cultured cells in previous studies. Cells with severely reduced expression of LIG3 maintain normal mtDNA copy number and respiration but show reduced viability in the face of alkylating and oxidative damage, increased mtDNA degradation in response to oxidative damage, and slow recovery from mtDNA depletion. Our findings clarify the cellular role of LIG3 and establish that the loss of viability in LIG3-deficient cells is conditional and secondary to the ρ(0) phenotype.

  16. Multiplexed SNP typing of ancient DNA clarifies the origin of Andaman mtDNA haplogroups amongst South Asian tribal populations.

    PubMed

    Endicott, Phillip; Metspalu, Mait; Stringer, Chris; Macaulay, Vincent; Cooper, Alan; Sanchez, Juan J

    2006-12-20

    The issue of errors in genetic data sets is of growing concern, particularly in population genetics where whole genome mtDNA sequence data is coming under increased scrutiny. Multiplexed PCR reactions, combined with SNP typing, are currently under-exploited in this context, but have the potential to genotype whole populations rapidly and accurately, significantly reducing the amount of errors appearing in published data sets. To show the sensitivity of this technique for screening mtDNA genomic sequence data, 20 historic samples of the enigmatic Andaman Islanders and 12 modern samples from three Indian tribal populations (Chenchu, Lambadi and Lodha) were genotyped for 20 coding region sites after provisional haplogroup assignment with control region sequences. The genotype data from the historic samples significantly revise the topologies for the Andaman M31 and M32 mtDNA lineages by rectifying conflicts in published data sets. The new Indian data extend the distribution of the M31a lineage to South Asia, challenging previous interpretations of mtDNA phylogeography. This genetic connection between the ancestors of the Andamanese and South Asian tribal groups approximately 30 kya has important implications for the debate concerning migration routes and settlement patterns of humans leaving Africa during the late Pleistocene, and indicates the need for more detailed genotyping strategies. The methodology serves as a low-cost, high-throughput model for the production and authentication of data from modern or ancient DNA, and demonstrates the value of museum collections as important records of human genetic diversity.

  17. Geographic Distribution of mtDNA Clades in the Tarnished Plant Bug (Lygus lineolaris) in North America

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The tarnished plant bug, Lygus lineolaris (Heteroptera: Miridae), is a polyphagous consumer of both crops and native plants. MtDNA sequences of the cox1 barcode region have revealed two clades separated by 3 nucleotide substitutions. While the species can be found throughout North America, it is mos...

  18. Trading genes along the silk road: mtDNA sequences and the origin of central Asian populations.

    PubMed Central

    Comas, D; Calafell, F; Mateu, E; Pérez-Lezaun, A; Bosch, E; Martínez-Arias, R; Clarimon, J; Facchini, F; Fiori, G; Luiselli, D; Pettener, D; Bertranpetit, J

    1998-01-01

    Central Asia is a vast region at the crossroads of different habitats, cultures, and trade routes. Little is known about the genetics and the history of the population of this region. We present the analysis of mtDNA control-region sequences in samples of the Kazakh, the Uighurs, the lowland Kirghiz, and the highland Kirghiz, which we have used to address both the population history of the region and the possible selective pressures that high altitude has on mtDNA genes. Central Asian mtDNA sequences present features intermediate between European and eastern Asian sequences, in several parameters-such as the frequencies of certain nucleotides, the levels of nucleotide diversity, mean pairwise differences, and genetic distances. Several hypotheses could explain the intermediate position of central Asia between Europe and eastern Asia, but the most plausible would involve extensive levels of admixture between Europeans and eastern Asians in central Asia, possibly enhanced during the Silk Road trade and clearly after the eastern and western Eurasian human groups had diverged. Lowland and highland Kirghiz mtDNA sequences are very similar, and the analysis of molecular variance has revealed that the fraction of mitochondrial genetic variance due to altitude is not significantly different from zero. Thus, it seems unlikely that altitude has exerted a major selective pressure on mitochondrial genes in central Asian populations. PMID:9837835

  19. Segregation of mtDNA Throughout Human Embryofetal Development: m.3243A > G as a Model System

    PubMed Central

    Monnot, Sophie; Gigarel, Nadine; Samuels, David C; Burlet, Philippe; Hesters, Laetitia; Frydman, Nelly; Frydman, René; Kerbrat, Violaine; Funalot, Benoit; Martinovic, Jelena; Benachi, Alexandra; Feingold, Josué; Munnich, Arnold; Bonnefont, Jean-Paul; Steffann, Julie

    2011-01-01

    Mitochondrial DNA (mtDNA) mutations cause a wide range of serious diseases with high transmission risk and maternal inheritance. Tissue heterogeneity of the heteroplasmy rate (“mutant load”) accounts for the wide phenotypic spectrum observed in carriers. Owing to the absence of therapy, couples at risk to transmit such disorders commonly ask for prenatal (PND) or preimplantation diagnosis (PGD). The lack of data regarding heteroplasmy distribution throughout intrauterine development, however, hampers the implementation of such procedures. We tracked the segregation of the m.3243A > G mutation (MT-TL1 gene) responsible for the MELAS syndrome in the developing embryo/fetus, using tissues and cells from eight carrier females, their 38 embryos and 12 fetuses. Mutant mtDNA segregation was found to be governed by random genetic drift, during oogenesis and somatic tissue development. The size of the bottleneck operating for m.3243A > G during oogenesis was shown to be individual-dependent. Comparison with data we achieved for the m.8993T > G mutation (MT-ATP6 gene), responsible for the NARP/Leigh syndrome, indicates that these mutations differentially influence mtDNA segregation during oogenesis, while their impact is similar in developing somatic tissues. These data have major consequences for PND and PGD procedures in mtDNA inherited disorders. Hum Mutat 32:116–125, 2011. © 2010 Wiley-Liss, Inc. PMID:21120938

  20. Mitochondrial DNA Ligase Is Dispensable for the Viability of Cultured Cells but Essential for mtDNA Maintenance*

    PubMed Central

    Shokolenko, Inna N.; Fayzulin, Rafik Z.; Katyal, Sachin; McKinnon, Peter J.; Wilson, Glenn L.; Alexeyev, Mikhail F.

    2013-01-01

    Multiple lines of evidence support the notion that DNA ligase III (LIG3), the only DNA ligase found in mitochondria, is essential for viability in both whole organisms and in cultured cells. Previous attempts to generate cells devoid of mitochondrial DNA ligase failed. Here, we report, for the first time, the derivation of viable LIG3-deficient mouse embryonic fibroblasts. These cells lack mtDNA and are auxotrophic for uridine and pyruvate, which may explain the apparent lethality of the Lig3 knock-out observed in cultured cells in previous studies. Cells with severely reduced expression of LIG3 maintain normal mtDNA copy number and respiration but show reduced viability in the face of alkylating and oxidative damage, increased mtDNA degradation in response to oxidative damage, and slow recovery from mtDNA depletion. Our findings clarify the cellular role of LIG3 and establish that the loss of viability in LIG3-deficient cells is conditional and secondary to the ρ0 phenotype. PMID:23884459

  1. Screen for abnormal mitochondrial phenotypes in mouse embryonic stem cells identifies a model for succinyl-CoA ligase deficiency and mtDNA depletion

    PubMed Central

    Donti, Taraka R.; Stromberger, Carmen; Ge, Ming; Eldin, Karen W.; Craigen, William J.; Graham, Brett H.

    2014-01-01

    ABSTRACT Mutations in subunits of succinyl-CoA synthetase/ligase (SCS), a component of the citric acid cycle, are associated with mitochondrial encephalomyopathy, elevation of methylmalonic acid (MMA), and mitochondrial DNA (mtDNA) depletion. A FACS-based retroviral-mediated gene trap mutagenesis screen in mouse embryonic stem (ES) cells for abnormal mitochondrial phenotypes identified a gene trap allele of Sucla2 (Sucla2SAβgeo), which was used to generate transgenic mice. Sucla2 encodes the ADP-specific β-subunit isoform of SCS. Sucla2SAβgeo homozygotes exhibited recessive lethality, with most mutants dying late in gestation (e18.5). Mutant placenta and embryonic (e17.5) brain, heart and muscle showed varying degrees of mtDNA depletion (20–60%). However, there was no mtDNA depletion in mutant liver, where the gene is not normally expressed. Elevated levels of MMA were observed in embryonic brain. SCS-deficient mouse embryonic fibroblasts (MEFs) demonstrated a 50% reduction in mtDNA content compared with wild-type MEFs. The mtDNA depletion resulted in reduced steady state levels of mtDNA encoded proteins and multiple respiratory chain deficiencies. mtDNA content could be restored by reintroduction of Sucla2. This mouse model of SCS deficiency and mtDNA depletion promises to provide insights into the pathogenesis of mitochondrial diseases with mtDNA depletion and into the biology of mtDNA maintenance. In addition, this report demonstrates the power of a genetic screen that combines gene trap mutagenesis and FACS analysis in mouse ES cells to identify mitochondrial phenotypes and to develop animal models of mitochondrial dysfunction. PMID:24271779

  2. The mitochondrial DNA makeup of Romanians: A forensic mtDNA control region database and phylogenetic characterization.

    PubMed

    Turchi, Chiara; Stanciu, Florin; Paselli, Giorgia; Buscemi, Loredana; Parson, Walther; Tagliabracci, Adriano

    2016-09-01

    To evaluate the pattern of Romanian population from a mitochondrial perspective and to establish an appropriate mtDNA forensic database, we generated a high-quality mtDNA control region dataset from 407 Romanian subjects belonging to four major historical regions: Moldavia, Transylvania, Wallachia and Dobruja. The entire control region (CR) was analyzed by Sanger-type sequencing assays and the resulting 306 different haplotypes were classified into haplogroups according to the most updated mtDNA phylogeny. The Romanian gene pool is mainly composed of West Eurasian lineages H (31.7%), U (12.8%), J (10.8%), R (10.1%), T (9.1%), N (8.1%), HV (5.4%),K (3.7%), HV0 (4.2%), with exceptions of East Asian haplogroup M (3.4%) and African haplogroup L (0.7%). The pattern of mtDNA variation observed in this study indicates that the mitochondrial DNA pool is geographically homogeneous across Romania and that the haplogroup composition reveals signals of admixture of populations of different origin. The PCA scatterplot supported this scenario, with Romania located in southeastern Europe area, close to Bulgaria and Hungary, and as a borderland with respect to east Mediterranean and other eastern European countries. High haplotype diversity (0.993) and nucleotide diversity indices (0.00838±0.00426), together with low random match probability (0.0087) suggest the usefulness of this control region dataset as a forensic database in routine forensic mtDNA analysis and in the investigation of maternal genetic lineages in the Romanian population.

  3. Analysis of mtDNA, miR-155 and BACH1 expression in hearts from donors with and without Down syndrome.

    PubMed

    Hefti, Erik; Quiñones-Lombraña, Adolfo; Redzematovic, Almedina; Hui, Jeffrey; Blanco, Javier G

    2016-01-01

    Cancer patients with Down syndrome (DS) are at increased risk for anthracycline-related cardiotoxicity. Mitochondrial DNA (mtDNA) alterations in hearts with-DS may contribute to anthracycline-related cardiotoxicity. Cardiac mtDNA and the mtDNA(4977) deletion were quantitated in samples with- (n = 11) and without-DS (n = 31). Samples with-DS showed 30% lower mtDNA (DS(MT-ND1/18Sratio): 1.48 ± 0.72 versus non-DS(MT-ND1/18Sratio): 2.10 ± 1.59; p = 0.647) and 30% higher frequency of the mtDNA(4977) deletion (DS(% frequency mtDNA(4977)) deletion: 0.0086 ± 0.0166 versus non-DS(% frequency mtDNA(4977)) deletion: 0.0066 ± 0.0124, p = 0.514) than samples without-DS. The BACH1 and microRNA-155 (miR-155) genes are located in chromosome 21, and their products have demonstrated roles during oxidative stress. BACH1 and miR-155 expression did not differ in hearts with- and without-DS. An association between BACH1 and miR-155 expression was detected in hearts without-DS, suggesting alterations between BACH1-miR-155 interactions in the DS settings.

  4. PCA and clustering reveal alternate mtDNA phylogeny of N and M clades.

    PubMed

    Alexe, G; Satya, R Vijaya; Seiler, M; Platt, D; Bhanot, T; Hui, S; Tanaka, M; Levine, A J; Bhanot, G

    2008-11-01

    Phylogenetic trees based on mtDNA polymorphisms are often used to infer the history of recent human migrations. However, there is no consensus on which method to use. Most methods make strong assumptions which may bias the choice of polymorphisms and result in computational complexity which limits the analysis to a few samples/polymorphisms. For example, parsimony minimizes the number of mutations, which biases the results to minimizing homoplasy events. Such biases may miss the global structure of the polymorphisms altogether, with the risk of identifying a "common" polymorphism as ancient without an internal check on whether it either is homoplasic or is identified as ancient because of sampling bias (from oversampling the population with the polymorphism). A signature of this problem is that different methods applied to the same data or the same method applied to different datasets results in different tree topologies. When the results of such analyses are combined, the consensus trees have a low internal branch consensus. We determine human mtDNA phylogeny from 1737 complete sequences using a new, direct method based on principal component analysis (PCA) and unsupervised consensus ensemble clustering. PCA identifies polymorphisms representing robust variations in the data and consensus ensemble clustering creates stable haplogroup clusters. The tree is obtained from the bifurcating network obtained when the data are split into k = 2,3,4,...,kmax clusters, with equal sampling from each haplogroup. Our method assumes only that the data can be clustered into groups based on mutations, is fast, is stable to sample perturbation, uses all significant polymorphisms in the data, works for arbitrary sample sizes, and avoids sample choice and haplogroup size bias. The internal branches of our tree have a 90% consensus accuracy. In conclusion, our tree recreates the standard phylogeny of the N, M, L0/L1, L2, and L3 clades, confirming the African origin of modern humans

  5. MtDNA control region variation affirms diversity and deep sub-structure in populations from southern Africa

    PubMed Central

    2013-01-01

    Background The current San and Khoe populations are remnant groups of a much larger and widely dispersed population of hunter-gatherers and pastoralists, who had exclusive occupation of southern Africa before the influx of Bantu-speakers from 2 ka (ka = kilo annum [thousand years] old/ago) and sea-borne immigrants within the last 350 years. Here we use mitochondrial DNA (mtDNA) to examine the population structure of various San and Khoe groups, including seven different Khoe-San groups (Ju/’hoansi, !Xun, /Gui+//Gana, Khwe, ≠Khomani, Nama and Karretjie People), three different Coloured groups and seven other comparative groups. MtDNA hyper variable segments I and II (HVS I and HVS II) together with selected mtDNA coding region SNPs were used to assign 538 individuals to 18 haplogroups encompassing 245 unique haplotypes. Data were further analyzed to assess haplogroup histories and the genetic affinities of the various San, Khoe and Coloured populations. Where possible, we tentatively contextualize the genetic trends through time against key trends known from the archaeological record. Results The most striking observation from this study was the high frequencies of the oldest mtDNA haplogroups (L0d and L0k) that can be traced back in time to ~100 ka, found at high frequencies in Khoe-San and sampled Coloured groups. Furthermore, the L0d/k sub-haplogroups were differentially distributed in the different Khoe-San and Coloured groups and had different signals of expansion, which suggested different associated demographic histories. When populations were compared to each other, San groups from the northern parts of southern Africa (Ju speaking: !Xun, Ju/’hoansi and Khoe-speaking: /Gui+//Gana) grouped together and southern groups (historically Tuu speaking: ≠Khomani and Karretjie People and some Coloured groups) grouped together. The Khoe group (Nama) clustered with the southern Khoe-San and Coloured groups. The Khwe mtDNA profile was very different from other

  6. Polymorphisms in DNA polymerase γ affect the mtDNA stability and the NRTI-induced mitochondrial toxicity in Saccharomyces cerevisiae

    PubMed Central

    Baruffini, Enrico; Ferrari, Jessica; Dallabona, Cristina; Donnini, Claudia; Lodi, Tiziana

    2015-01-01

    Several pathological mutations have been identified in human POLG gene, encoding for the catalytic subunit of Pol γ, the solely mitochondrial replicase in animals and fungi. However, little is known regarding non-pathological polymorphisms found in this gene. Here we studied, in the yeast model Saccharomyces cerevisiae, eight human polymorphisms. We found that most of them are not neutral but enhanced both mtDNA extended mutability and the accumulation of mtDNA point mutations, either alone or in combination with a pathological mutation. In addition, we found that the presence of some SNPs increased the stavudine and/or zalcitabine-induced mtDNA mutability and instability. PMID:25462018

  7. Regional Variation in mtDNA of the Lesser Prairie-Chicken

    USGS Publications Warehouse

    Hagen, Christian A.; Pitman, James C.; Sandercock, Brett K.; Wolfe, Don H.; Robel, Robel J.; Applegate, Roger D.; Oyler-McCance, Sara J.

    2010-01-01

    Cumulative loss of habitat and long-term decline in the populations of the Lesser Prairie-Chicken (Tympanuchus pallidicinctus) have led to concerns for the species' viability throughout its range in the southern Great Plains. For more efficient conservation past and present distributions of genetic variation need to be understood. We examined the distribution of mitochondrial DNA (mtDNA) variation in the Lesser Prairie-Chicken across Kansas, Colorado, Oklahoma, and New Mexico. Throughout the range we found little genetic differentiation except for the population in New Mexico, which was significantly different from most other publications. We did, however, find significant isolation by distance at the rangewide scale (r=0.698). We found no relationship between haplotype phylogeny and geography, and our analyses provide evidence for a post-glacial population expansion within the species that is consistent with the idea that speciation within Tympanuchus is recent. Conservation actions that increase the likelihood of genetically viable populations in the future should be evaluated for implementation.

  8. Mosaic gene conversion after a tandem duplication of mtDNA sequence in Diomedeidae (albatrosses).

    PubMed

    Eda, Masaki; Kuro-o, Masaki; Higuchi, Hiroyoshi; Hasegawa, Hiroshi; Koike, Hiroko

    2010-04-01

    Although the tandem duplication of mitochondrial (mt) sequences, especially those of the control region (CR), has been detected in metazoan species, few studies have focused on the features of the duplicated sequence itself, such as the gene conversion rate, distribution patterns of the variation, and relative rates of evolution between the copies. To investigate the features of duplicated mt sequences, we partially sequenced the mt genome of 16 Phoebastria albatrosses belonging to three species (P. albatrus, P. nigripes, and P. immutabilis). More than 2,300 base pairs of tandemly-duplicated sequence were shared by all three species. The observed gene arrangement was shared in the three Phoebastria albatrosses and suggests that the duplication event occurred in the common ancestor of the three species. Most of the copies in each individual were identical or nearly identical, and were maintained through frequent gene conversions. By contrast, portions of CR domains I and III had different phylogenetic signals, suggesting that gene conversion had not occurred in those sections after the speciation of the three species. Several lines of data, including the heterogeneity of the rate of molecular evolution, nucleotide differences, and putative secondary structures, suggests that the two sequences in CR domain I are maintained through selection; however, additional studies into the mechanisms of gene conversion and mtDNA synthesis are required to confirm this hypothesis.

  9. Rampant Nuclear Insertion of mtDNA across Diverse Lineages within Orthoptera (Insecta)

    PubMed Central

    Song, Hojun; Moulton, Matthew J.; Whiting, Michael F.

    2014-01-01

    Nuclear mitochondrial pseudogenes (numts) are non-functional fragments of mtDNA inserted into the nuclear genome. Numts are prevalent across eukaryotes and a positive correlation is known to exist between the number of numts and the genome size. Most numt surveys have relied on model organisms with fully sequenced nuclear genomes, but such analyses have limited utilities for making a generalization about the patterns of numt accumulation for any given clade. Among insects, the order Orthoptera is known to have the largest nuclear genome and it is also reported to include several species with a large number of numts. In this study, we use Orthoptera as a case study to document the diversity and abundance of numts by generating numts of three mitochondrial loci across 28 orthopteran families, representing the phylogenetic diversity of the order. We discover that numts are rampant in all lineages, but there is no discernable and consistent pattern of numt accumulation among different lineages. Likewise, we do not find any evidence that a certain mitochondrial gene is more prone to nuclear insertion than others. We also find that numt insertion must have occurred continuously and frequently throughout the diversification of Orthoptera. Although most numts are the result of recent nuclear insertion, we find evidence of very ancient numt insertion shared by highly divergent families dating back to the Jurassic period. Finally, we discuss several factors contributing to the extreme prevalence of numts in Orthoptera and highlight the importance of exploring the utility of numts in evolutionary studies. PMID:25333882

  10. Ancestral Puebloan mtDNA in Context of the Greater Southwest

    PubMed Central

    Durand, Kathy R.; Smith, David Glenn

    2010-01-01

    Ancient DNA (aDNA) was extracted from the human remains of seventy-three individuals from the Tommy and Mine Canyon sites (dated to PI-II and PIII, respectively), located on the B-Square Ranch in the Middle San Juan region of New Mexico. The mitochondrial DNA (mtDNA) haplogroups of forty-eight (65.7%) of these samples were identified, and their frequency distributions were compared with those of other prehistoric and modern populations from the Greater Southwest and Mexico. The haplogroup frequency distributions for the two sites were statistically significantly different from each other, with the Mine Canyon site exhibiting an unusually high frequency of haplogroup A for a Southwestern population, indicating the possible influence of migration or other evolutionary forces. However, both sites exhibited a relatively high frequency of haplogroup B, typical of Southwestern populations, suggesting continuity in the Southwest, as has been hypothesized by others (S. Carlyle 2003; Carlyle, et al. 2000; Kemp 2006; Malhi, et al. 2003; Smith, et al. 2000). The first hypervariable region of twenty-three individuals (31.5%) was also sequenced to confirm haplogroup assignments and compared with other sequences from the region. This comparison further strengthens the argument for population continuity in the Southwest without a detectable influence from Mesoamerica. PMID:20514346

  11. Identification of Polynesian mtDNA haplogroups in remains of Botocudo Amerindians from Brazil

    PubMed Central

    Gonçalves, Vanessa Faria; Stenderup, Jesper; Rodrigues-Carvalho, Cláudia; Silva, Hilton P.; Gonçalves-Dornelas, Higgor; Líryo, Andersen; Kivisild, Toomas; Malaspinas, Anna-Sapfo; Campos, Paula F.; Rasmussen, Morten; Willerslev, Eske; Pena, Sergio Danilo J.

    2013-01-01

    There is a consensus that modern humans arrived in the Americas 15,000–20,000 y ago during the Late Pleistocene, most probably from northeast Asia through Beringia. However, there is still debate about the time of entry and number of migratory waves, including apparent inconsistencies between genetic and morphological data on Paleoamericans. Here we report the identification of mitochondrial sequences belonging to haplogroups characteristic of Polynesians in DNA extracted from ancient skulls of the now extinct Botocudo Indians from Brazil. The identification of these two Polynesian haplogroups was confirmed in independent replications in Brazil and Denmark, ensuring reliability of the data. Parallel analysis of 12 other Botocudo individuals yielded only the well-known Amerindian mtDNA haplogroup C1. Potential scenarios to try to help understand these results are presented and discussed. The findings of this study may be relevant for the understanding of the pre-Columbian and/or post-Columbian peopling of the Americas. PMID:23576724

  12. Rampant nuclear insertion of mtDNA across diverse lineages within Orthoptera (Insecta).

    PubMed

    Song, Hojun; Moulton, Matthew J; Whiting, Michael F

    2014-01-01

    Nuclear mitochondrial pseudogenes (numts) are non-functional fragments of mtDNA inserted into the nuclear genome. Numts are prevalent across eukaryotes and a positive correlation is known to exist between the number of numts and the genome size. Most numt surveys have relied on model organisms with fully sequenced nuclear genomes, but such analyses have limited utilities for making a generalization about the patterns of numt accumulation for any given clade. Among insects, the order Orthoptera is known to have the largest nuclear genome and it is also reported to include several species with a large number of numts. In this study, we use Orthoptera as a case study to document the diversity and abundance of numts by generating numts of three mitochondrial loci across 28 orthopteran families, representing the phylogenetic diversity of the order. We discover that numts are rampant in all lineages, but there is no discernable and consistent pattern of numt accumulation among different lineages. Likewise, we do not find any evidence that a certain mitochondrial gene is more prone to nuclear insertion than others. We also find that numt insertion must have occurred continuously and frequently throughout the diversification of Orthoptera. Although most numts are the result of recent nuclear insertion, we find evidence of very ancient numt insertion shared by highly divergent families dating back to the Jurassic period. Finally, we discuss several factors contributing to the extreme prevalence of numts in Orthoptera and highlight the importance of exploring the utility of numts in evolutionary studies.

  13. Autosomal recessive Wolfram syndrome associated with an 8.5 kb mtDNA single deletion

    SciTech Connect

    Barrientos, A.; Casademont, J.; Cardellach, F.

    1996-05-01

    Wolfram syndrome (MIM 222300) is characterized by optic atrophy, diabetes mellitus, diabetes insipidus, neurosensory hearing loss, urinary tract abnormalities, and neurological dysfunction. The association of clinical manifestations in tissues and organs unrelated functionally or embryologically suggested the possibility of a mitochondrial implication in the disease, which has been demonstrated in two sporadic cases. Nonetheless, familial studies suggested an autosomal recessive mode of transmission, and recent data demonstrated linkage with markers on the short arm of human chromosome 4. The patient reported here, as well as her parents and unaffected sister, carried a heteroplasmic 8.5-kb deletion in mtDNA. The deletion accounted for 23% of mitochondrial genomes in lymphocytes from the patient and {approximately}5% in the tissues studied from members of her family. The presence of the deletion in the patient in a proportion higher than in her unaffected parents suggests a putative defect in a nuclear gene that acts at the mitochondrial level. 39 refs., 6 figs., 3 tabs.

  14. Forensic and phylogeographic characterisation of mtDNA lineages from Somalia.

    PubMed

    Mikkelsen, Martin; Fendt, Liane; Röck, Alexander W; Zimmermann, Bettina; Rockenbauer, Eszter; Hansen, Anders J; Parson, Walther; Morling, Niels

    2012-07-01

    The African mitochondrial (mt) phylogeny is coarsely resolved but the majority of population data generated so far is limited to the analysis of the first hypervariable segment (HVS-1) of the control region (CR). Therefore, this study aimed on the investigation of the entire CR of 190 unrelated Somali individuals to enrich the severely underrepresented African mtDNA pool. The majority (60.5 %) of the haplotypes were of sub-Saharan origin with L0a1d, L2a1h and L3f being the most frequently observed haplogroups. This is in sharp contrast to previous data reported from the Y-chromosome, where only about 5 % of the observed haplogroups were of sub-Saharan provenance. We compared the genetic distances based on population pairwise F (st) values between 11 published East, Central and North African as well as western Asian populations and the Somali sequences and displayed them in a multi-dimensional scaling plot. Genetic proximity evidenced by clustering roughly reflected the relative geographic location of the populations. The sequences will be included in the EMPOP database ( www.empop.org ) under accession number EMP00397 upon publication (Parson and Dür Forensic Sci Int Genet 1:88-92, 2007).

  15. Evaluation of cytochrome b mtDNA sequences in genetic diversity studies of Channa marulius (Channidae: Perciformes).

    PubMed

    Habib, Maria; Lakra, W S; Mohindra, Vindhya; Khare, Praveen; Barman, A S; Singh, Akanksha; Lal, Kuldeep K; Punia, Peyush; Khan, Asif A

    2011-02-01

    Channa marulius (Hamilton, 1822) is a commercially important freshwater fish and a potential candidate species for aquaculture. The present study evaluated partial Cytochrome b gene sequence of mtDNA for determining the genetic variation in wild populations of C. marulius. Genomic DNA extracted from C. marulius samples (n = 23) belonging to 3 distant rivers; Mahanadi, Teesta and Yamuna was analyzed. Sequencing of 307 bp Cytochrome b mtDNA fragment revealed the presence of 5 haplotypes with haplotype diversity value of 0.763 and nucleotide diversity value of 0.0128. Single population specific haplotype was observed in Mahanadi and Yamuna samples and 3 haplotypes in Teesta samples. The analysis of data demonstrated the suitability of partial Cytochrome b sequence in determining the genetic diversity in C. marulius population.

  16. Association of mitochondrial haplogroup J and mtDNA oxidative damage in two different North Spain elderly populations.

    PubMed

    Domínguez-Garrido, Elena; Martínez-Redondo, Diana; Martín-Ruiz, Carmen; Gómez-Durán, Aurora; Ruiz-Pesini, Eduardo; Madero, Pilar; Tamparillas, Manuel; Montoya, Julio; von Zglinicki, Thomas; Díez-Sánchez, Carmen; López-Pérez, Manuel J

    2009-08-01

    This work investigates the association between longevity, mitochondrial DNA (mtDNA) variants and oxidative DNA damage in an older than 85 years population. The participants, similar in genetic and cultural background as well as gender distribution, come from villages near to the Pyrenees Mountains (900-1,400 m altitude) (n = 69) and the Ebro's Valley (200-300 m altitude) (n = 69) in Spain. Our results show an accumulation of the haplogroup J in elderly individuals with an over-representation of J2 in Pyrenees group but not in the Ebro's Valley, the former associating with a diminished DNA damage. In conclusion, our results suggest that J mitochondrial variant, that induce lower mtDNA damage, could present a phenotypic survival advantage to environmental conditions and, thus, accumulate in elderly population.

  17. A7445G mtDNA mutation present in a Portuguese family exhibiting hereditary deafness and palmoplantar keratoderma.

    PubMed

    Caria, H; Matos, T; Oliveira-Soares, R; Santos, A R; Galhardo, I; Soares-Almeida, L; Dias, O; Andrea, M; Correia, C; Fialho, G

    2005-07-01

    Mitochondrial DNA (mtDNA) A7445G point mutation has been shown to be responsible for familial nonepidermolytic palmoplantar keratoderma (NEPPK) associated with deafness without any additional features. To date, only a few cases have been described. We report a Portuguese pedigree presenting an inherited combination of NEPPK and sensorineural deafness compatible with maternal transmission. Clinical expression and age of onset of NEPPK and deafness were variable. Normal expression patterns of epidermal keratins and filaggrin, intercellular junction proteins including connexin 26, loricrin and cornified envelope proteins, were observed. Molecular analysis revealed that all the affected members, previously screened for Cx26 mutations with negative results, presented the mtDNA A7445G point mutation in the homoplasmic form. To our knowledge, this is the fifth family in whom inherited NEPPK and hearing loss are related to this mitochondrial mutation.

  18. Multiple hypothesis correction is vital and undermines reported mtDNA links to diseases including AIDS, cancer, and Huntingdon's.

    PubMed

    Johnston, Iain G

    2016-09-01

    The ability to sequence mitochondrial genomes quickly and cheaply has led to an explosion in available mtDNA data. As a result, an expanding literature is exploring links between mtDNA features and susceptibility to, or prevalence of, a range of diseases. Unfortunately, this great technological power has not always been accompanied by great statistical responsibility. I will focus on one aspect of statistical analysis, multiple hypothesis correction, that is absolutely required, yet often absolutely ignored, for responsible interpretation of this literature. Many existing studies perform comparisons between incidences of a large number (N) of different mtDNA features and a given disease, reporting all those yielding p values under 0.05 as significant links. But when many comparisons are performed, it is highly likely that several p values under 0.05 will emerge, by chance, in the absence of any underlying link. A suitable correction (for example, Bonferroni correction, requiring p < 0.05/N) must, therefore, be employed to avoid reporting false positive results. The absence of such corrections means that there is good reason to believe that many links reported between mtDNA features and various diseases are false; a state of affairs that is profoundly negative both for fundamental biology and for public health. I will show that statistics matching those claimed to illustrate significant links can arise, with a high probability, when no such link exists, and that these claims should thus be discarded until results of suitable statistical reliability are provided. I also discuss some strategies for responsible analysis and interpretation of this literature.

  19. A new subclade of mtDNA haplogroup C1 found in Icelanders: evidence of pre-Columbian contact?

    PubMed

    Ebenesersdóttir, Sigríður Sunna; Sigurðsson, Asgeir; Sánchez-Quinto, Federico; Lalueza-Fox, Carles; Stefánsson, Kári; Helgason, Agnar

    2011-01-01

    Although most mtDNA lineages observed in contemporary Icelanders can be traced to neighboring populations in the British Isles and Scandinavia, one may have a more distant origin. This lineage belongs to haplogroup C1, one of a handful that was involved in the settlement of the Americas around 14,000 years ago. Contrary to an initial assumption that this lineage was a recent arrival, preliminary genealogical analyses revealed that the C1 lineage was present in the Icelandic mtDNA pool at least 300 years ago. This raised the intriguing possibility that the Icelandic C1 lineage could be traced to Viking voyages to the Americas that commenced in the 10th century. In an attempt to shed further light on the entry date of the C1 lineage into the Icelandic mtDNA pool and its geographical origin, we used the deCODE Genetics genealogical database to identify additional matrilineal ancestors that carry the C1 lineage and then sequenced the complete mtDNA genome of 11 contemporary C1 carriers from four different matrilines. Our results indicate a latest possible arrival date in Iceland of just prior to 1700 and a likely arrival date centuries earlier. Most surprisingly, we demonstrate that the Icelandic C1 lineage does not belong to any of the four known Native American (C1b, C1c, and C1d) or Asian (C1a) subclades of haplogroup C1. Rather, it is presently the only known member of a new subclade, C1e. While a Native American origin seems most likely for C1e, an Asian or European origin cannot be ruled out.

  20. Circumpolar diversity and geographic differentiation of mtDNA in the critically endangered Antarctic blue whale (Balaenoptera musculus intermedia).

    PubMed

    Sremba, Angela L; Hancock-Hanser, Brittany; Branch, Trevor A; LeDuc, Rick L; Baker, C Scott

    2012-01-01

    The Antarctic blue whale (Balaenoptera musculus intermedia) was hunted to near extinction between 1904 and 1972, declining from an estimated initial abundance of more than 250,000 to fewer than 400. Here, we describe mtDNA control region diversity and geographic differentiation in the surviving population of the Antarctic blue whale, using 218 biopsy samples collected under the auspices of the International Whaling Commission (IWC) during research cruises from 1990-2009. Microsatellite genotypes and mtDNA sequences identified 166 individuals among the 218 samples and documented movement of a small number of individuals, including a female that traveled at least 6,650 km or 131° longitude over four years. mtDNA sequences from the 166 individuals were aligned with published sequences from 17 additional individuals, resolving 52 unique haplotypes from a consensus length of 410 bp. From this minimum census, a rarefaction analysis predicted that only 72 haplotypes (95% CL, 64, 86) have survived in the contemporary population of Antarctic blue whales. However, haplotype diversity was relatively high (0.968±0.004), perhaps as a result of the longevity of blue whales and the relatively recent timing of the bottleneck. Despite the potential for circumpolar dispersal, we found significant differentiation in mtDNA diversity (F(ST) = 0.032, p<0.005) and microsatellite alleles (F(ST) = 0.005, p<0.05) among the six Antarctic Areas historically used by the IWC for management of blue whales.

  1. Extreme Mitochondrial Evolution in the Ctenophore Mnemiopsis leidyi: Insights from mtDNA and the Nuclear Genome

    PubMed Central

    Pett, Walker; Ryan, Joseph F.; Pang, Kevin; Mullikin, James C.; Martindale, Mark Q.; Baxevanis, Andreas D.; Lavrov, Dennis V.

    2012-01-01

    Recent advances in sequencing technology have led to a rapid accumulation of mitochondrial DNA (mtDNA) sequences, which now represent the wide spectrum of animal diversity. However, one animal phylum – Ctenophora – has, to date, remained completely unsampled. Ctenophores, a small group of marine animals, are of interest due to their unusual biology, controversial phylogenetic position, and devastating impact as an invasive species. Using data from the Mnemiopsis leidyi genome sequencing project, we PCR amplified and analyzed its complete mitochondrial (mt-) genome. At just over 10kb, the mt-genome of M. leidyi is the smallest animal mtDNA ever reported and is among the most derived. It has lost at least 25 genes, including atp6 and all tRNA genes. We show that atp6 has been relocated to the nuclear genome and has acquired introns and a mitochondrial targeting presequence, while tRNA genes have been genuinely lost, along with nuclear-encoded mt-aminoacyl tRNA synthetases. The mt-genome of M. leidyi also displays extremely high rates of sequence evolution, which likely led to the degeneration of both protein and rRNA genes. In particular, encoded rRNA molecules possess little similarity with their homologues in other organisms and have highly reduced secondary structures. At the same time, nuclear encoded mt-ribosomal proteins have undergone expansions, probably to compensate for the reductions in mt-rRNA. The unusual features identified in M. leidyi mtDNA make this organism an interesting system for the study of various aspects of mitochondrial biology, particularly protein and tRNA import and mt-ribosome structures, and add to its value as an emerging model species. Furthermore, the fast-evolving M. leidyi mtDNA should be a convenient molecular marker for species- and population-level studies. PMID:21985407

  2. The genetic relationship between the Finns and the Finnish Saami (Lapps): analysis of nuclear DNA and mtDNA.

    PubMed

    Lahermo, P; Sajantila, A; Sistonen, P; Lukka, M; Aula, P; Peltonen, L; Savontaus, M L

    1996-06-01

    The genetic relationships between two Finno-Ugric-speaking populations, the Finns and the Finnish Saami (Lapps), were studied by using PCR for six nuclear-DNA marker loci, mitochondrial restriction-site polymorphism, and sequence variation of a 360-bp segment of the mitochondrial control region. The allele frequencies of each of the nuclear-DNA marker loci and the frequencies of mtDNA restriction haplotypes were significantly different between the populations. The Saami showed exceptionally low variation in their mtDNA restriction sites. The 9-bp deletion common in East Asian populations was not observed, nor did the haplotype data fit into the haplogroup categorization of Torroni et al. The average number of nucleotide substitutions from the mtDNA haplotype data indicated that the Finnish Saami may be closer to the Finns than to the other reference populations, whereas nuclear DNA suggested that the Finns are more closely related to the European reference populations than to the Finnish Saami. The similarity of the Finns to the other Europeans was even more pronounced according to the sequence data. We were unable to distinguish between the Finns and either the Swiss or Sardinian reference populations, whereas the Finnish Saami clearly stood apart. The Finnish Saami are distinct from other Circumarctic populations, although two of the lineages found among the Saami showed closer relationship to the Circumarctic than to the European lineages. The sequence data indicated an exceptionally high divergence for the Saami mtDNA control lineages. The distribution of the pairwise nucleotide differences in the Saami suggested that this population has not experienced an expansion similar to what was indicated for the Finns and the reference populations.

  3. A mitochondrial DNA (mtDNA) mutation associated with maternally inherited Parkinson`s disease (PD) and deafness

    SciTech Connect

    Shoffner, J.M.; Brown, M.; Huoponen, K.

    1994-09-01

    A pedigree was characterized in which PD and deafness is expressed along the maternal lineage. The proband is 74 years old and has PD. Her mother and 3 of 7 siblings have PD and a maternal lineage cousin may have early signs of PD. The proband`s mother, a sibling, and all four of her daughters have premature deafness. Since manifestations of PD begin after 50 years of age, the 30-40 year old daughters have not reached an age where extrapyramidal symptoms are likely to appear. Although all 4 daughters have premature deafness, one daughter experienced a rapid reduction of her hearing after receiving a short course during childhood of the aminoglycoside streptomycin. Muscle biopsies from the proband who has PD and 3 daughters with deafness revealed normal histology. Oxidative phosphorylation biochemistry showed Complex I and IV defects in the proband and 2 daughters and a Complex I defect in the other daughter. The proband`s mtDNA was sequenced. Of the nucleotide variants observed, the only significant nucleotide change was a homoplasmic A-to-G point mutation in the 12S rRNA gene at position 1555 of the mtDNA. This site is homologous to the E. coli aminoglycoside binding site and has been found in a large Arab-Israeli pedigree with spontaneously occurring deafness and three Chinese pedigrees with aminoglycoside-induced deafness. Hence, this family shows a direct link between PD, deafness, Complex I and IV defects, and a mutation in a gene that functions in mitochondrial protein synthesis. Furthermore, the interaction between aminoglycosides and the mtDNA in a manner that augments the pathogenic effects of this mutation provides an excellent example of how environmental toxins and mtDNA mutations can interact to give a spectrum of clinical presentations.

  4. Extreme mitochondrial evolution in the ctenophore Mnemiopsis leidyi: Insight from mtDNA and the nuclear genome.

    PubMed

    Pett, Walker; Ryan, Joseph F; Pang, Kevin; Mullikin, James C; Martindale, Mark Q; Baxevanis, Andreas D; Lavrov, Dennis V

    2011-08-01

    Recent advances in sequencing technology have led to a rapid accumulation of mitochondrial DNA (mtDNA) sequences, which now represent the wide spectrum of animal diversity. However, one animal phylum--Ctenophora--has, to date, remained completely unsampled. Ctenophores, a small group of marine animals, are of interest due to their unusual biology, controversial phylogenetic position, and devastating impact as invasive species. Using data from the Mnemiopsis leidyi genome sequencing project, we Polymerase Chain Reaction (PCR) amplified and analyzed its complete mitochondrial (mt-) genome. At just over 10 kb, the mt-genome of M. leidyi is the smallest animal mtDNA ever reported and is among the most derived. It has lost at least 25 genes, including atp6 and all tRNA genes. We show that atp6 has been relocated to the nuclear genome and has acquired introns and a mitochondrial targeting presequence, while tRNA genes have been genuinely lost, along with nuclear-encoded mt-aminoacyl tRNA synthetases. The mt-genome of M. leidyi also displays extremely high rates of sequence evolution, which likely led to the degeneration of both protein and rRNA genes. In particular, encoded rRNA molecules possess little similarity with their homologs in other organisms and have highly reduced secondary structures. At the same time, nuclear encoded mt-ribosomal proteins have undergone expansions, likely to compensate for the reductions in mt-rRNA. The unusual features identified in M. leidyi mtDNA make this organism an interesting system for the study of various aspects of mitochondrial biology, particularly protein and tRNA import and mt-ribosome structures, and add to its value as an emerging model species. Furthermore, the fast-evolving M. leidyi mtDNA should be a convenient molecular marker for species- and population-level studies.

  5. Effect of thyroid hormone on mitochondrial properties and oxidative stress in cells from patients with mtDNA defects.

    PubMed

    Menzies, Keir J; Robinson, Brian H; Hood, David A

    2009-02-01

    Mitochondrial (mt)DNA mutations contribute to various disease states characterized by low ATP production. In contrast, thyroid hormone [3,3',5-triiodothyronine (T(3))] induces mitochondrial biogenesis and enhances ATP generation within cells. To evaluate the role of T(3)-mediated mitochondrial biogenesis in patients with mtDNA mutations, three fibroblast cell lines with mtDNA mutations were evaluated, including two patients with Leigh's syndrome and one with hypertrophic cardiomyopathy. Compared with control cells, patient fibroblasts displayed similar levels of mitochondrial mass, peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), mitochondrial transcription factor A (Tfam), and uncoupling protein 2 (UCP2) protein expression. However, patient cells exhibited a 1.6-fold elevation in ROS production, a 1.7-fold elevation in cytoplasmic Ca2+ levels, a 1.2-fold elevation in mitochondrial membrane potential, and 30% less complex V activity compared with control cells. Patient cells also displayed 20-25% reductions in both cytochrome c oxidase (COX) activity and MnSOD protein levels compared with control cells. After T(3) treatment of patient cells, ROS production was decreased by 40%, cytoplasmic Ca2+ was reduced by 20%, COX activity was increased by 1.3-fold, and ATP levels were elevated by 1.6-fold, despite the absence of a change in mitochondrial mass. There were no significant alterations in the protein expression of PGC-1alpha, Tfam, or UCP2 in either T(3)-treated patient or control cells. However, T(3) restored the mitochondrial membrane potential, complex V activity, and levels of MnSOD to normal values in patient cells and elevated MnSOD levels by 21% in control cells. These results suggest that T(3) acts to reduce cellular oxidative stress, which may help attenuate ROS-mediated damage, along with improving mitochondrial function and energy status in cells with mtDNA defects.

  6. Possible role of mtDNA depletion and respiratory chain defects in aristolochic acid I-induced acute nephrotoxicity

    SciTech Connect

    Jiang, Zhenzhou Bao, Qingli Sun, Lixin Huang, Xin Wang, Tao Zhang, Shuang Li, Han Zhang, Luyong

    2013-01-15

    This report describes an investigation of the pathological mechanism of acute renal failure caused by toxic tubular necrosis after treatment with aristolochic acid I (AAI) in Sprague–Dawley (SD) rats. The rats were gavaged with AAI at 0, 5, 20, or 80 mg/kg/day for 7 days. The pathologic examination of the kidneys showed severe acute tubular degenerative changes primarily affecting the proximal tubules. Supporting these results, we detected significantly increased concentrations of blood urea nitrogen (BUN) and creatinine (Cr) in the rats treated with AAI, indicating damage to the kidneys. Ultrastructural examination showed that proximal tubular mitochondria were extremely enlarged and dysmorphic with loss and disorientation of their cristae. Mitochondrial function analysis revealed that the two indicators for mitochondrial energy metabolism, the respiratory control ratio (RCR) and ATP content, were reduced in a dose-dependent manner after AAI treatment. The RCR in the presence of substrates for complex I was reduced more significantly than in the presence of substrates for complex II. In additional experiments, the activity of respiratory complex I, which is partly encoded by mitochondrial DNA (mtDNA), was more significantly impaired than that of respiratory complex II, which is completely encoded by nuclear DNA (nDNA). A real-time PCR assay revealed a marked reduction of mtDNA in the kidneys treated with AAI. Taken together, these results suggested that mtDNA depletion and respiratory chain defects play critical roles in the pathogenesis of kidney injury induced by AAI, and that the same processes might contribute to aristolochic acid-induced nephrotoxicity in humans. -- Highlights: ► AAI-induced acute renal failure in rats and the proximal tubule was the target. ► Tubular mitochondria were morphologically aberrant in ultrastructural examination. ► AAI impair mitochondrial bioenergetic function and mtDNA replication.

  7. Anthropology. Comment on "Late Pleistocene human skeleton and mtDNA link Paleoamericans and modern Native Americans".

    PubMed

    Prüfer, Kay; Meyer, Matthias

    2015-02-20

    Chatters et al. (Reports, 16 May 2014, p. 750) reported the retrieval of DNA sequences from a 12,000- to 13,000-year-old human tooth discovered in an underwater cave in Mexico's Yucatan peninsula. They propose that this ancient human individual's mitochondrial DNA (mtDNA) belongs to haplogroup D1. However, our analysis of postmortem damage patterns finds no evidence for an ancient origin of these sequences.

  8. Anthropology. Response to Comment on "Late Pleistocene human skeleton and mtDNA link Paleoamericans and modern Native Americans".

    PubMed

    Kemp, Brian M; Lindo, John; Bolnick, Deborah A; Malhi, Ripan S; Chatters, James C

    2015-02-20

    Prüfer and Meyer raise concerns over the mitochondrial DNA (mtDNA) results we reported for the Hoyo Negro individual, citing failure of a portion of these data to conform to their expectations of ancient DNA (aDNA). Because damage patterns in aDNA vary, outright rejection of our findings on this basis is unwarranted, especially in light of our other observations.

  9. The genetic relationship between the Finns and the Finnish Saami (Lapps): analysis of nuclear DNA and mtDNA.

    PubMed Central

    Lahermo, P.; Sajantila, A.; Sistonen, P.; Lukka, M.; Aula, P.; Peltonen, L.; Savontaus, M. L.

    1996-01-01

    The genetic relationships between two Finno-Ugric-speaking populations, the Finns and the Finnish Saami (Lapps), were studied by using PCR for six nuclear-DNA marker loci, mitochondrial restriction-site polymorphism, and sequence variation of a 360-bp segment of the mitochondrial control region. The allele frequencies of each of the nuclear-DNA marker loci and the frequencies of mtDNA restriction haplotypes were significantly different between the populations. The Saami showed exceptionally low variation in their mtDNA restriction sites. The 9-bp deletion common in East Asian populations was not observed, nor did the haplotype data fit into the haplogroup categorization of Torroni et al. The average number of nucleotide substitutions from the mtDNA haplotype data indicated that the Finnish Saami may be closer to the Finns than to the other reference populations, whereas nuclear DNA suggested that the Finns are more closely related to the European reference populations than to the Finnish Saami. The similarity of the Finns to the other Europeans was even more pronounced according to the sequence data. We were unable to distinguish between the Finns and either the Swiss or Sardinian reference populations, whereas the Finnish Saami clearly stood apart. The Finnish Saami are distinct from other Circumarctic populations, although two of the lineages found among the Saami showed closer relationship to the Circumarctic than to the European lineages. The sequence data indicated an exceptionally high divergence for the Saami mtDNA control lineages. The distribution of the pairwise nucleotide differences in the Saami suggested that this population has not experienced an expansion similar to what was indicated for the Finns and the reference populations. Images Figure 1 PMID:8651309

  10. Cigarette toxicity triggers Leber's hereditary optic neuropathy by affecting mtDNA copy number, oxidative phosphorylation and ROS detoxification pathways

    PubMed Central

    Giordano, L; Deceglie, S; d'Adamo, P; Valentino, M L; La Morgia, C; Fracasso, F; Roberti, M; Cappellari, M; Petrosillo, G; Ciaravolo, S; Parente, D; Giordano, C; Maresca, A; Iommarini, L; Del Dotto, V; Ghelli, A M; Salomao, S R; Berezovsky, A; Belfort, R; Sadun, A A; Carelli, V; Loguercio Polosa, P; Cantatore, P

    2015-01-01

    Leber's hereditary optic neuropathy (LHON), the most frequent mitochondrial disease, is associated with mitochondrial DNA (mtDNA) point mutations affecting Complex I subunits, usually homoplasmic. This blinding disorder is characterized by incomplete penetrance, possibly related to several genetic modifying factors. We recently reported that increased mitochondrial biogenesis in unaffected mutation carriers is a compensatory mechanism, which reduces penetrance. Also, environmental factors such as cigarette smoking have been implicated as disease triggers. To investigate this issue further, we first assessed the relationship between cigarette smoke and mtDNA copy number in blood cells from large cohorts of LHON families, finding that smoking was significantly associated with the lowest mtDNA content in affected individuals. To unwrap the mechanism of tobacco toxicity in LHON, we exposed fibroblasts from affected individuals, unaffected mutation carriers and controls to cigarette smoke condensate (CSC). CSC decreased mtDNA copy number in all cells; moreover, it caused significant reduction of ATP level only in mutated cells including carriers. This implies that the bioenergetic compensation in carriers is hampered by exposure to smoke derivatives. We also observed that in untreated cells the level of carbonylated proteins was highest in affected individuals, whereas the level of several detoxifying enzymes was highest in carriers. Thus, carriers are particularly successful in reactive oxygen species (ROS) scavenging capacity. After CSC exposure, the amount of detoxifying enzymes increased in all cells, but carbonylated proteins increased only in LHON mutant cells, mostly from affected individuals. All considered, it appears that exposure to smoke derivatives has a more deleterious effect in affected individuals, whereas carriers are the most efficient in mitigating ROS rather than recovering bioenergetics. Therefore, the identification of genetic modifiers that

  11. The role of microglial mtDNA damage in age-dependent prolonged LPS-induced sickness behavior.

    PubMed

    Nakanishi, Hiroshi; Hayashi, Yoshinori; Wu, Zhou

    2011-02-01

    Microglia are the main cellular source of oxidation products and inflammatory molecules in the brain during aging. The accumulation of mitochondrial DNA (mtDNA) oxidative damage in microglia during aging results in the increased production of reactive oxygen species (ROS). The increased intracellular ROS, in turn, activates a redox-sensitive nuclear factor-κB (NF-κB) to provoke excessive neuroinflammation, resulting in memory deficits and the prolonged behavioral consequence of infection. Besides its role in regulating the gene copy number, mitochondrial transcription factor A (TFAM) is closely associated with the stabilization of mtDNA structures. Lipopolysaccharide (LPS) induces the generation of ROS from the actively respirating mitochondria as well as NADPH oxidase, and leads to the subsequent activation of the NF-κB-dependent inflammatory pathway in aging microglia. The overexpression of human TFAM improves the age-dependent prolonged LPS-induced sickness behaviors by ameliorating the mtDNA damage and reducing the resultant redox-regulated inflammatory responses. Therefore, 'microglia-aging' plays important roles in the age-dependent enhanced behavioral consequences of infection.

  12. The mitochondrial genome of Hydra oligactis (Cnidaria, Hydrozoa) sheds new light on animal mtDNA evolution and cnidarian phylogeny.

    PubMed

    Kayal, Ehsan; Lavrov, Dennis V

    2008-02-29

    The 16,314-nuceotide sequence of the linear mitochondrial DNA (mtDNA) molecule of Hydra oligactis (Cnidaria, Hydrozoa)--the first from the class Hydrozoa--has been determined. This sequence contains genes for 13 energy pathway proteins, small and large subunit rRNAs, and methionine and tryptophan tRNAs, as is typical for cnidarians. All genes have the same transcriptional orientation and their arrangement in the genome is similar to that of the jellyfish Aurelia aurita. In addition, a partial copy of cox1 is present at one end of the molecule in a transcriptional orientation opposite to the rest of the genes, forming a part of inverted terminal repeat characteristic of linear mtDNA and linear mitochondrial plasmids. The sequence close to at least one end of the molecule contains several homonucleotide runs as well as small inverted repeats that are able to form strong secondary structures and may be involved in mtDNA maintenance and expression. Phylogenetic analysis of mitochondrial genes of H. oligactis and other cnidarians supports the Medusozoa hypothesis but also suggests that Anthozoa may be paraphyletic, with octocorallians more closely related to the Medusozoa than to the Hexacorallia. The latter inference implies that Anthozoa is paraphyletic and that the polyp (rather than a medusa) is the ancestral body type in Cnidaria.

  13. Degradation of paternal mitochondria after fertilization: implications for heteroplasmy, assisted reproductive technologies and mtDNA inheritance.

    PubMed

    Sutovsky, Peter; Van Leyen, Klaus; McCauley, Tod; Day, Billy N; Sutovsky, Miriam

    2004-01-01

    Maternal inheritance of mitochondrial DNA has long been regarded as a major paradox in developmental biology. While some confusion may still persist in popular science, research data clearly document that the paternal sperm-borne mitochondria of most mammalian species enter the ooplasm at fertilization and are specifically targeted for degradation by the resident ubiquitin system. Ubiquitin is a proteolytic chaperone that forms covalently linked polyubiquitin chains on the targeted proteinaceous substrates. The polyubiquitin tag redirects the substrate proteins to a 26-S proteasome, a multi-subunit proteolytic organelle. Thus, specific proteasomal inhibitors reversibly block sperm mitochondrial degradation in ooplasm. Lysosomal degradation and the activity of membrane-lipoperoxidating enzyme 15-lipoxygenase (15-LOX) may also contribute to sperm mitochondrial degradation in the ooplasm, but probably is not crucial. Prohibitin, the major protein of the inner mitochondrial membrane, appears to be ubiquitinated in the sperm mitochondria. Occasional occurrence of paternal inheritance of mtDNA has been suggested in mammals including humans. While most such evidence has been widely disputed, it warrants further examination. Of particular concern is the documented heteroplasmy, i.e. mixed mtDNA inheritance after ooplasmic transplantation. Intracytoplasmic sperm injection (ICSI) has inherent potential for delaying the degradation of sperm mitochondria. However, paternal mtDNA inheritance after ICSI has not been documented so far.

  14. Functional Characterization of Three Concomitant MtDNA LHON Mutations Shows No Synergistic Effect on Mitochondrial Activity.

    PubMed

    Cruz-Bermúdez, Alberto; Vicente-Blanco, Ramiro J; Hernández-Sierra, Rosana; Montero, Mayte; Alvarez, Javier; González Manrique, Mar; Blázquez, Alberto; Martín, Miguel Angel; Ayuso, Carmen; Garesse, Rafael; Fernández-Moreno, Miguel A

    2016-01-01

    The presence of more than one non-severe pathogenic mutation in the same mitochondrial DNA (mtDNA) molecule is very rare. Moreover, it is unclear whether their co-occurrence results in an additive impact on mitochondrial function relative to single mutation effects. Here we describe the first example of a mtDNA molecule harboring three Leber's hereditary optic neuropathy (LHON)-associated mutations (m.11778G>A, m.14484T>C, m.11253T>C) and the analysis of its genetic, biochemical and molecular characterization in transmitochondrial cells (cybrids). Extensive characterization of cybrid cell lines harboring either the 3 mutations or the single classic m.11778G>A and m.14484T>C mutations revealed no differences in mitochondrial function, demonstrating the absence of a synergistic effect in this model system. These molecular results are in agreement with the ophthalmological characteristics found in the triple mutant patient, which were similar to those carrying single mtDNA LHON mutations.

  15. Different genetic components in the Norwegian population revealed by the analysis of mtDNA and Y chromosome polymorphisms.

    PubMed

    Passarino, Giuseppe; Cavalleri, Gianpiero L; Lin, Alice A; Cavalli-Sforza, Luigi Luca; Børresen-Dale, Anne-Lise; Underhill, Peter A

    2002-09-01

    The genetic composition of the Norwegian population was investigated by analysing polymorphisms associated with both the mitochondrial DNA (mtDNA) and Y chromosome loci in a sample of 74 Norwegian males. The combination of their uniparental mode of inheritance and the absence of recombination make these haplotypic stretches of DNA the tools of choice in evaluating the different components of a population's gene pool. The sequencing of the Dloop and two diagnostic RFLPs (AluI 7025 and HinfI at 12 308) allowed us to classify the mtDNA molecules in 10 previously described groups. As for the Y chromosome the combination of binary markers and microsatellites allowed us to compare our results to those obtained elsewhere in Europe. Both mtDNA and Y chromosome polymorphisms showed a noticeable genetic affinity between Norwegians and central Europeans, especially Germans. When the phylogeographic analysis of the Y chromosome haplotypes was attempted some interesting clues on the peopling of Norway emerged. Although Y chromosome binary and microsatellite data indicate that 80% of the haplotypes are closely related to Central and western Europeans, the remainder share a unique binary marker (M17) common in eastern Europeans with informative microsatellite haplotypes suggesting a different demographic history. Other minor genetic influences on the Norwegian population from Uralic speakers and Mediterranean populations were also highlighted.

  16. Transmitochondrial mito-miceΔ and mtDNA mutator mice, but not aged mice, share the same spectrum of musculoskeletal disorders.

    PubMed

    Mito, Takayuki; Ishizaki, Hikari; Suzuki, Michiko; Morishima, Hitomi; Ota, Azusa; Ishikawa, Kaori; Nakada, Kazuto; Maeno, Akiteru; Shiroishi, Toshihiko; Hayashi, Jun-Ichi

    2015-01-24

    The spectra of phenotypes associated with aging and mitochondrial diseases sometimes appear to overlap with each other. We used aged mice and a mouse model of mitochondrial diseases (transmitochondrial mito-miceΔ with deleted mtDNA) to study whether premature aging phenotypes observed in mtDNA mutator mice are associated with aging or mitochondrial diseases. Here, we provide convincing evidence that all the mice examined had musculoskeletal disorders of osteoporosis and muscle atrophy, which correspond to phenotypes prevalently observed in the elderly. However, precise investigation of musculoskeletal disorders revealed that the spectra of osteoporosis and muscle atrophy phenotypes in mtDNA mutator mice were very close to those in mito-miceΔ, but different from those of aged mice. Therefore, mtDNA mutator mice and mito-miceΔ, but not aged mice, share the spectra of musculoskeletal disorders.

  17. Identification of mtDNA mutation in a pedigree with gestational diabetes, deafness, Wolff-Parkinson-White syndrome and placenta accreta.

    PubMed

    Aggarwal, P; Gill-Randall, R; Wheatley, T; Buchalter, M B; Metcalfe, J; Alcolado, J C

    2001-01-01

    Mitochondrial DNA (mtDNA) defects are associated with a number of human disorders. Although many occur sporadically, maternal transmission is the hallmark of diseases due to mtDNA point mutations. The same mutation may manifest strikingly different phenotypes; for example, the A to G substitution at np 3243 was first reported in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episodes (the MELAS syndrome), but is also found in patients with diabetes and deafness. Here we present a case of gestational diabetes, deafness, premature greying, placenta accreta and Wolff-Parkinson-White (WPW) syndrome associated with a mtDNA mutation. Although this is the first report of such an association, study of 27 other patients with WPW syndrome failed to confirm that this mtDNA mutation is a common cause of such pre-excitation disorders.

  18. Super-resolution microscopy reveals that mammalian mitochondrial nucleoids have a uniform size and frequently contain a single copy of mtDNA.

    PubMed

    Kukat, Christian; Wurm, Christian A; Spåhr, Henrik; Falkenberg, Maria; Larsson, Nils-Göran; Jakobs, Stefan

    2011-08-16

    Mammalian mtDNA is packaged in DNA-protein complexes denoted mitochondrial nucleoids. The organization of the nucleoid is a very fundamental question in mitochondrial biology and will determine tissue segregation and transmission of mtDNA. We have used a combination of stimulated emission depletion microscopy, enabling a resolution well below the diffraction barrier, and molecular biology to study nucleoids in a panel of mammalian tissue culture cells. We report that the nucleoids labeled with antibodies against DNA, mitochondrial transcription factor A (TFAM), or incorporated BrdU, have a defined, uniform mean size of ∼100 nm in mammals. Interestingly, the nucleoid frequently contains only a single copy of mtDNA (average ∼1.4 mtDNA molecules per nucleoid). Furthermore, we show by molecular modeling and volume calculations that TFAM is a main constituent of the nucleoid, besides mtDNA. These fundamental insights into the organization of mtDNA have broad implications for understanding mitochondrial dysfunction in disease and aging.

  19. mtDNA variation in East Africa unravels the history of Afro-Asiatic groups.

    PubMed

    Boattini, Alessio; Castrì, Loredana; Sarno, Stefania; Useli, Antonella; Cioffi, Manuela; Sazzini, Marco; Garagnani, Paolo; De Fanti, Sara; Pettener, Davide; Luiselli, Donata

    2013-03-01

    East Africa (EA) has witnessed pivotal steps in the history of human evolution. Due to its high environmental and cultural variability, and to the long-term human presence there, the genetic structure of modern EA populations is one of the most complicated puzzles in human diversity worldwide. Similarly, the widespread Afro-Asiatic (AA) linguistic phylum reaches its highest levels of internal differentiation in EA. To disentangle this complex ethno-linguistic pattern, we studied mtDNA variability in 1,671 individuals (452 of which were newly typed) from 30 EA populations and compared our data with those from 40 populations (2970 individuals) from Central and Northern Africa and the Levant, affiliated to the AA phylum. The genetic structure of the studied populations--explored using spatial Principal Component Analysis and Model-based clustering--turned out to be composed of four clusters, each with different geographic distribution and/or linguistic affiliation, and signaling different population events in the history of the region. One cluster is widespread in Ethiopia, where it is associated with different AA-speaking populations, and shows shared ancestry with Semitic-speaking groups from Yemen and Egypt and AA-Chadic-speaking groups from Central Africa. Two clusters included populations from Southern Ethiopia, Kenya and Tanzania. Despite high and recent gene-flow (Bantu, Nilo-Saharan pastoralists), one of them is associated with a more ancient AA-Cushitic stratum. Most North-African and Levantine populations (AA-Berber, AA-Semitic) were grouped in a fourth and more differentiated cluster. We therefore conclude that EA genetic variability, although heavily influenced by migration processes, conserves traces of more ancient strata.

  20. African origin for Madagascan dogs revealed by mtDNA analysis

    PubMed Central

    Ardalan, Arman; Oskarsson, Mattias C. R.; van Asch, Barbara; Rabakonandriania, Elisabeth; Savolainen, Peter

    2015-01-01

    Madagascar was one of the last major land masses to be inhabited by humans. It was initially colonized by Austronesian speaking Indonesians 1500–2000 years ago, but subsequent migration from Africa has resulted in approximately equal genetic contributions from Indonesia and Africa, and the material culture has mainly African influences. The dog, along with the pig and the chicken, was part of the Austronesian Neolithic culture, and was furthermore the only domestic animal to accompany humans to every continent in ancient times. To illuminate Madagascan cultural origins and track the initial worldwide dispersal of dogs, we here investigated the ancestry of Madagascan dogs. We analysed mtDNA control region sequences in dogs from Madagascar (n=145) and compared it with that from potential ancestral populations in Island Southeast Asia (n=219) and sub-Saharan Africa (n=493). We found that 90% of the Madagascan dogs carried a haplotype that was also present in sub-Saharan Africa and that the remaining lineages could all be attributed to a likely origin in Africa. By contrast, only 26% of Madagascan dogs shared haplotypes with Indonesian dogs, and one haplotype typical for Austronesian dogs, carried by more than 40% of Indonesian and Polynesian dogs, was absent among the Madagascan dogs. Thus, in contrast to the human population, Madagascan dogs seem to trace their origin entirely from Africa. These results suggest that dogs were not brought to Madagascar by the initial Austronesian speaking colonizers on their transoceanic voyage, but were introduced at a later stage, together with human migration and cultural influence from Africa. PMID:26064658

  1. Autosomal and mtDNA Markers Affirm the Distinctiveness of Lions in West and Central Africa.

    PubMed

    Bertola, Laura D; Tensen, Laura; van Hooft, Pim; White, Paula A; Driscoll, Carlos A; Henschel, Philipp; Caragiulo, Anthony; Dias-Freedman, Isabela; Sogbohossou, Etotépé A; Tumenta, Pricelia N; Jirmo, Tuqa H; de Snoo, Geert R; de Iongh, Hans H; Vrieling, Klaas

    2015-01-01

    The evolutionary history of a species is key for understanding the taxonomy and for the design of effective management strategies for species conservation. The knowledge about the phylogenetic position of the lion (Panthera leo) in West/Central Africa is largely based on mitochondrial markers. Previous studies using mtDNA only have shown this region to hold a distinct evolutionary lineage. In addition, anthropogenic factors have led to a strong decline in West/Central African lion numbers, thus, the conservation value of these populations is particularly high. Here, we investigate whether autosomal markers are concordant with previously described phylogeographic patterns, and confirm the unique position of the West/Central African lion. Analysis of 20 microsatellites and 1,454 bp of the mitochondrial DNA in 16 lion populations representing the entire geographic range of the species found congruence in both types of markers, identifying four clusters: 1) West/Central Africa, 2) East Africa, 3) Southern Africa and 4) India. This is not in line with the current taxonomy, as defined by the IUCN, which only recognizes an African and an Asiatic subspecies. There are no indications that genetic diversity in West/Central Africa lions is lower than in either East or Southern Africa, however, given this genetic distinction and the recent declines of lion numbers in this region, we strongly recommend prioritization of conservation projects in West/Central Africa. As the current taxonomic nomenclature does not reflect the evolutionary history of the lion, we suggest that a taxonomic revision of the lion is warranted.

  2. Autosomal and mtDNA Markers Affirm the Distinctiveness of Lions in West and Central Africa

    PubMed Central

    Bertola, Laura D.; Tensen, Laura; van Hooft, Pim; White, Paula A.; Driscoll, Carlos A.; Henschel, Philipp; Caragiulo, Anthony; Dias-Freedman, Isabela; Sogbohossou, Etotépé A.; Tumenta, Pricelia N.; Jirmo, Tuqa H.; de Snoo, Geert R.

    2015-01-01

    The evolutionary history of a species is key for understanding the taxonomy and for the design of effective management strategies for species conservation. The knowledge about the phylogenetic position of the lion (Panthera leo) in West/Central Africa is largely based on mitochondrial markers. Previous studies using mtDNA only have shown this region to hold a distinct evolutionary lineage. In addition, anthropogenic factors have led to a strong decline in West/Central African lion numbers, thus, the conservation value of these populations is particularly high. Here, we investigate whether autosomal markers are concordant with previously described phylogeographic patterns, and confirm the unique position of the West/Central African lion. Analysis of 20 microsatellites and 1,454 bp of the mitochondrial DNA in 16 lion populations representing the entire geographic range of the species found congruence in both types of markers, identifying four clusters: 1) West/Central Africa, 2) East Africa, 3) Southern Africa and 4) India. This is not in line with the current taxonomy, as defined by the IUCN, which only recognizes an African and an Asiatic subspecies. There are no indications that genetic diversity in West/Central Africa lions is lower than in either East or Southern Africa, however, given this genetic distinction and the recent declines of lion numbers in this region, we strongly recommend prioritization of conservation projects in West/Central Africa. As the current taxonomic nomenclature does not reflect the evolutionary history of the lion, we suggest that a taxonomic revision of the lion is warranted. PMID:26466139

  3. Is homoplasy or lineage sorting the source of incongruent mtdna and nuclear gene trees in the stiff-tailed ducks (Nomonyx-Oxyura)?

    PubMed

    McCracken, Kevin; Sorenson, Michael

    2005-02-01

    We evaluated the potential effects of homoplasy, ancestral polymorphism, and hybridization as obstacles to resolving phylogenetic relationships within Nomonyx-Oxyura stiff-tailed ducks (Oxyurinae; subtribe Oxyurina). Mitochondrial DNA (mtDNA) control region sequences from 94 individuals supported monophyly of mtDNA haplotypes for each of the six species and provided no evidence of extant incomplete lineage sorting or inter-specific hybridization. The ruddy ducks (O. j. jamaicensis,O. j. andina, O. j. ferruginea) are each others' closest relatives, but the lack of shared haplotypes between O. j. jamaicensis and O. j. ferruginea suggests long-standing historical isolation. In contrast, O. j. andina shares haplotypes with O. j. jamaicensis and O. j. ferruginea, which supports Todd's (1979) and Fjeldså's (1986) hypothesis that O. j. andina is an intergrade or hybrid subspecies of O. j. jamaicensis and O. j. ferruginea. Control region data and a much larger data set composed of approximately 8800 base pairs of mitochondrial and nuclear sequence for each species indicate that the two New World species, O. vittata and O. jamaicensis, branch basally within Oxyura. A clade of three Old World species (O. australis, O. maccoa, O. leucocephala) is well supported, but different loci and also different characters within the mtDNA data support three different resolutions of the Old World clade, yielding an essentially unresolved trichotomy. Fundamentally different factors limited the resolution of the mtDNA and nuclear gene trees. Gene trees for most nuclear loci were unresolved due to slow rates of mutation and a lack of informative variation, whereas uncertain resolution of the mtDNA gene tree was due to homoplasy. Within the mtDNA, approximately equal numbers of characters supported each of three possible resolutions. Parametric and nonparametric bootstrap analyses suggest that resolution of the mtDNA tree based on ~4300 bp per taxon is uncertain but that complete mtDNA

  4. Results of the 2003-2004 GEP-ISFG collaborative study on mitochondrial DNA: focus on the mtDNA profile of a mixed semen-saliva stain.

    PubMed

    Crespillo, Manuel; Paredes, Miguel R; Prieto, Lourdes; Montesino, Marta; Salas, Antonio; Albarran, Cristina; Alvarez-Iglesias, V; Amorin, Antonio; Berniell-Lee, Gemma; Brehm, Antonio; Carril, Juan C; Corach, Daniel; Cuevas, Nerea; Di Lonardo, Ana M; Doutremepuich, Christian; Espinheira, Rosa M; Espinoza, Marta; Gómez, Felix; González, Alberto; Hernández, Alexis; Hidalgo, M; Jimenez, Magda; Leite, Fabio P N; López, Ana M; López-Soto, Manuel; Lorente, Jose A; Pagano, Shintia; Palacio, Ana M; Pestano, José J; Pinheiro, Maria F; Raimondi, Eduardo; Ramón, M M; Tovar, Florangel; Vidal-Rioja, Lidia; Vide, Maria C; Whittle, Martín R; Yunis, Juan J; Garcia-Hirschfel, Julia

    2006-07-13

    We report here a review of the seventh mitochondrial DNA (mtDNA) exercise undertaken by the Spanish and Portuguese working group (GEP) of the International Society for Forensic Genetics (ISFG) corresponding to the period 2003-2004. Five reference bloodstains from five donors (M1-M5), a mixed stain of saliva and semen (M6), and a hair sample (M7) were submitted to each participating laboratory for nuclear DNA (nDNA; autosomal STR and Y-STR) and mtDNA analysis. Laboratories were asked to investigate the contributors of samples M6 and M7 among the reference donors (M1-M5). A total of 34 laboratories reported total or partial mtDNA sequence data from both, the reference bloodstains (M1-M5) and the hair sample (M7) concluding a match between mtDNA profiles of M5 and M7. Autosomal STR and Y-STR profiling was the preferred strategy to investigate the contributors of the semen/saliva mixture (M6). Nuclear DNA profiles were consistent with a mixture of saliva from the donor (female) of M4 and semen from donor M5, being the semen (XY) profile the dominant component of the mixture. Strikingly, and in contradiction to the nuclear DNA analysis, mtDNA sequencing results yield a more simple result: only the saliva contribution (M4) was detected, either after preferential lysis or after complete DNA digestion. Some labs provided with several explanations for this finding and carried out additional experiments to explain this apparent contradictory result. The results pointed to the existence of different relative amounts of nuclear and mtDNAs in saliva and semen. We conclude that this circumstance could strongly influence the interpretation of the mtDNA evidence in unbalanced mixtures and in consequence lead to false exclusions. During the GEP-ISFG annual conference a validation study was planned to progress in the interpretation of mtDNA from different mixtures.

  5. A comparative analysis of Y chromosome and mtDNA phylogenies of the Hylobates gibbons

    PubMed Central

    2012-01-01

    Background The evolutionary relationships of closely related species have long been of interest to biologists since these species experienced different evolutionary processes in a relatively short period of time. Comparison of phylogenies inferred from DNA sequences with differing inheritance patterns, such as mitochondrial, autosomal, and X and Y chromosomal loci, can provide more comprehensive inferences of the evolutionary histories of species. Gibbons, especially the genus Hylobates, are particularly intriguing as they consist of multiple closely related species which emerged rapidly and live in close geographic proximity. Our current understanding of relationships among Hylobates species is largely based on data from the maternally-inherited mitochondrial DNAs (mtDNAs). Results To infer the paternal histories of gibbon taxa, we sequenced multiple Y chromosomal loci from 26 gibbons representing 10 species. As expected, we find levels of sequence variation some five times lower than observed for the mitochondrial genome (mtgenome). Although our Y chromosome phylogenetic tree shows relatively low resolution compared to the mtgenome tree, our results are consistent with the monophyly of gibbon genera suggested by the mtgenome tree. In a comparison of the molecular dating of divergences and on the branching patterns of phylogeny trees between mtgenome and Y chromosome data, we found: 1) the inferred divergence estimates were more recent for the Y chromosome than for the mtgenome, 2) the species H. lar and H. pileatus are monophyletic in the mtgenome phylogeny, respectively, but a H. pileatus individual falls into the H. lar Y chromosome clade. Conclusions Based on the ~6.4 kb of Y chromosomal DNA sequence data generated for each of the 26 individuals in this study, we provide molecular inferences on gibbon and particularly on Hylobates evolution complementary to those from mtDNA data. Overall, our results illustrate the utility of comparative studies of loci with

  6. Association of low race performance with mtDNA haplogroup L3b of Australian thoroughbred horses.

    PubMed

    Lin, Xiang; Zheng, Hong-Xiang; Davie, Allan; Zhou, Shi; Wen, Li; Meng, Jun; Zhang, Yong; Aladaer, Qimude; Liu, Bin; Liu, Wu-Jun; Yao, Xin-Kui

    2017-01-27

    Mitochondrial DNA (mtDNA) encodes the genes for respiratory chain sub-units that determine the efficiency of oxidative phosphorylation in mitochondria. The aim of this study was to determine if there were any haplogroups and variants in mtDNA that could be associated with athletic performance of Thoroughbred horses. The whole mitochondrial genomes of 53 maternally unrelated Australian Thoroughbred horses were sequenced and an association study was performed with the competition histories of 1123 horses within their maternal lineages. A horse mtDNA phylogenetic tree was constructed based on a total of 195 sequences (including 142 from previous reports). The association analysis showed that the sample groups with poor racing performance history were enriched in haplogroup L3b (p = .0003) and its sub-haplogroup L3b1a (p = .0007), while those that had elite performance appeared to be not significantly associated with haplogroups G2 and L3a1a1a (p > .05). Haplogroup L3b and L3b1a bear two and five specific variants of which variant T1458C (site 345 in 16s rRNA) is the only potential functional variant. Furthermore, secondary reconstruction of 16s RNA showed considerable differences between two types of 16s RNA molecules (with and without T1458C), indicating a potential functional effect. The results suggested that haplogroup L3b, could have a negative association with elite performance. The T1458C mutation harboured in haplogroup L3b could have a functional effect that is related to poor athletic performance.

  7. Contrasting patterns of Y chromosome and mtDNA variation in Africa: evidence for sex-biased demographic processes.

    PubMed

    Wood, Elizabeth T; Stover, Daryn A; Ehret, Christopher; Destro-Bisol, Giovanni; Spedini, Gabriella; McLeod, Howard; Louie, Leslie; Bamshad, Mike; Strassmann, Beverly I; Soodyall, Himla; Hammer, Michael F

    2005-07-01

    To investigate associations between genetic, linguistic, and geographic variation in Africa, we type 50 Y chromosome SNPs in 1122 individuals from 40 populations representing African geographic and linguistic diversity. We compare these patterns of variation with those that emerge from a similar analysis of published mtDNA HVS1 sequences from 1918 individuals from 39 African populations. For the Y chromosome, Mantel tests reveal a strong partial correlation between genetic and linguistic distances (r=0.33, P=0.001) and no correlation between genetic and geographic distances (r=-0.08, P>0.10). In contrast, mtDNA variation is weakly correlated with both language (r=0.16, P=0.046) and geography (r=0.17, P=0.035). AMOVA indicates that the amount of paternal among-group variation is much higher when populations are grouped by linguistics (Phi(CT)=0.21) than by geography (Phi(CT)=0.06). Levels of maternal genetic among-group variation are low for both linguistics and geography (Phi(CT)=0.03 and 0.04, respectively). When Bantu speakers are removed from these analyses, the correlation with linguistic variation disappears for the Y chromosome and strengthens for mtDNA. These data suggest that patterns of differentiation and gene flow in Africa have differed for men and women in the recent evolutionary past. We infer that sex-biased rates of admixture and/or language borrowing between expanding Bantu farmers and local hunter-gatherers played an important role in influencing patterns of genetic variation during the spread of African agriculture in the last 4000 years.

  8. The Phylogeny of the Four Pan-American MtDNA Haplogroups: Implications for Evolutionary and Disease Studies

    PubMed Central

    Achilli, Alessandro; Perego, Ugo A.; Bravi, Claudio M.; Coble, Michael D.; Kong, Qing-Peng; Woodward, Scott R.; Salas, Antonio; Torroni, Antonio; Bandelt, Hans-Jürgen

    2008-01-01

    Only a limited number of complete mitochondrial genome sequences belonging to Native American haplogroups were available until recently, which left America as the continent with the least amount of information about sequence variation of entire mitochondrial DNAs. In this study, a comprehensive overview of all available complete mitochondrial DNA (mtDNA) genomes of the four pan-American haplogroups A2, B2, C1, and D1 is provided by revising the information scattered throughout GenBank and the literature, and adding 14 novel mtDNA sequences. The phylogenies of haplogroups A2, B2, C1, and D1 reveal a large number of sub-haplogroups but suggest that the ancestral Beringian population(s) contributed only six (successful) founder haplotypes to these haplogroups. The derived clades are overall starlike with coalescence times ranging from 18,000 to 21,000 years (with one exception) using the conventional calibration. The average of about 19,000 years somewhat contrasts with the corresponding lower age of about 13,500 years that was recently proposed by employing a different calibration and estimation approach. Our estimate indicates a human entry and spread of the pan-American haplogroups into the Americas right after the peak of the Last Glacial Maximum and comfortably agrees with the undisputed ages of the earliest Paleoindians in South America. In addition, the phylogenetic approach also indicates that the pathogenic status proposed for various mtDNA mutations, which actually define branches of Native American haplogroups, was based on insufficient grounds. PMID:18335039

  9. Interference of Co-amplified nuclear mitochondrial DNA sequences on the determination of human mtDNA heteroplasmy by Using the SURVEYOR nuclease and the WAVE HS system.

    PubMed

    Yen, Hsiu-Chuan; Li, Shiue-Li; Hsu, Wei-Chien; Tang, Petrus

    2014-01-01

    High-sensitivity and high-throughput mutation detection techniques are useful for screening the homoplasmy or heteroplasmy status of mitochondrial DNA (mtDNA), but might be susceptible to interference from nuclear mitochondrial DNA sequences (NUMTs) co-amplified during polymerase chain reaction (PCR). In this study, we first evaluated the platform of SURVEYOR Nuclease digestion of heteroduplexed DNA followed by the detection of cleaved DNA by using the WAVE HS System (SN/WAVE-HS) for detecting human mtDNA variants and found that its performance was slightly better than that of denaturing high-performance liquid chromatography (DHPLC). The potential interference from co-amplified NUMTs on screening mtDNA heteroplasmy when using these 2 highly sensitive techniques was further examined by using 2 published primer sets containing a total of 65 primer pairs, which were originally designed to be used with one of the 2 techniques. We confirmed that 24 primer pairs could amplify NUMTs by conducting bioinformatic analysis and PCR with the DNA from 143B-ρ0 cells. Using mtDNA extracted from the mitochondria of human 143B cells and a cybrid line with the nuclear background of 143B-ρ0 cells, we demonstrated that NUMTs could affect the patterns of chromatograms for cell DNA during SN-WAVE/HS analysis of mtDNA, leading to incorrect judgment of mtDNA homoplasmy or heteroplasmy status. However, we observed such interference only in 2 of 24 primer pairs selected, and did not observe such effects during DHPLC analysis. These results indicate that NUMTs can affect the screening of low-level mtDNA variants, but it might not be predicted by bioinformatic analysis or the amplification of DNA from 143B-ρ0 cells. Therefore, using purified mtDNA from cultured cells with proven purity to evaluate the effects of NUMTs from a primer pair on mtDNA detection by using PCR-based high-sensitivity methods prior to the use of a primer pair in real studies would be a more practical strategy.

  10. Evolutionary Analyses of Entire Genomes Do Not Support the Association of mtDNA Mutations with Ras/MAPK Pathway Syndromes

    PubMed Central

    Cerezo, María; Balboa, Emilia; Heredia, Claudia; Castro-Feijóo, Lidia; Rica, Itxaso; Barreiro, Jesús; Eirís, Jesús; Cabanas, Paloma; Martínez-Soto, Isabel; Fernández-Toral, Joaquín; Castro-Gago, Manuel; Pombo, Manuel; Carracedo, Ángel; Barros, Francisco

    2011-01-01

    Background There are several known autosomal genes responsible for Ras/MAPK pathway syndromes, including Noonan syndrome (NS) and related disorders (such as LEOPARD, neurofibromatosis type 1), although mutations of these genes do not explain all cases. Due to the important role played by the mitochondrion in the energetic metabolism of cardiac muscle, it was recently proposed that variation in the mitochondrial DNA (mtDNA) genome could be a risk factor in the Noonan phenotype and in hypertrophic cardiomyopathy (HCM), which is a common clinical feature in Ras/MAPK pathway syndromes. In order to test these hypotheses, we sequenced entire mtDNA genomes in the largest series of patients suffering from Ras/MAPK pathway syndromes analyzed to date (n = 45), most of them classified as NS patients (n = 42). Methods/Principal Findings The results indicate that the observed mtDNA lineages were mostly of European ancestry, reproducing in a nutshell the expected haplogroup (hg) patterns of a typical Iberian dataset (including hgs H, T, J, and U). Three new branches of the mtDNA phylogeny (H1j1, U5b1e, and L2a5) are described for the first time, but none of these are likely to be related to NS or Ras/MAPK pathway syndromes when observed under an evolutionary perspective. Patterns of variation in tRNA and protein genes, as well as redundant, private and heteroplasmic variants, in the mtDNA genomes of patients were as expected when compared with the patterns inferred from a worldwide mtDNA phylogeny based on more than 8700 entire genomes. Moreover, most of the mtDNA variants found in patients had already been reported in healthy individuals and constitute common polymorphisms in human population groups. Conclusions/Significance As a whole, the observed mtDNA genome variation in the NS patients was difficult to reconcile with previous findings that indicated a pathogenic role of mtDNA variants in NS. PMID:21526175

  11. MMS Exposure Promotes Increased MtDNA Mutagenesis in the Presence of Replication-Defective Disease-Associated DNA Polymerase γ Variants

    PubMed Central

    Stumpf, Jeffrey D.; Copeland, William C.

    2014-01-01

    Mitochondrial DNA (mtDNA) encodes proteins essential for ATP production. Mutant variants of the mtDNA polymerase cause mutagenesis that contributes to aging, genetic diseases, and sensitivity to environmental agents. We interrogated mtDNA replication in Saccharomyces cerevisiae strains with disease-associated mutations affecting conserved regions of the mtDNA polymerase, Mip1, in the presence of the wild type Mip1. Mutant frequency arising from mtDNA base substitutions that confer erythromycin resistance and deletions between 21-nucleotide direct repeats was determined. Previously, increased mutagenesis was observed in strains encoding mutant variants that were insufficient to maintain mtDNA and that were not expected to reduce polymerase fidelity or exonuclease proofreading. Increased mutagenesis could be explained by mutant variants stalling the replication fork, thereby predisposing the template DNA to irreparable damage that is bypassed with poor fidelity. This hypothesis suggests that the exogenous base-alkylating agent, methyl methanesulfonate (MMS), would further increase mtDNA mutagenesis. Mitochondrial mutagenesis associated with MMS exposure was increased up to 30-fold in mip1 mutants containing disease-associated alterations that affect polymerase activity. Disrupting exonuclease activity of mutant variants was not associated with increased spontaneous mutagenesis compared with exonuclease-proficient alleles, suggesting that most or all of the mtDNA was replicated by wild type Mip1. A novel subset of C to G transversions was responsible for about half of the mutants arising after MMS exposure implicating error-prone bypass of methylated cytosines as the predominant mutational mechanism. Exposure to MMS does not disrupt exonuclease activity that suppresses deletions between 21-nucleotide direct repeats, suggesting the MMS-induce mutagenesis is not explained by inactivated exonuclease activity. Further, trace amounts of CdCl2 inhibit mtDNA replication but

  12. MMS exposure promotes increased MtDNA mutagenesis in the presence of replication-defective disease-associated DNA polymerase γ variants.

    PubMed

    Stumpf, Jeffrey D; Copeland, William C

    2014-10-01

    Mitochondrial DNA (mtDNA) encodes proteins essential for ATP production. Mutant variants of the mtDNA polymerase cause mutagenesis that contributes to aging, genetic diseases, and sensitivity to environmental agents. We interrogated mtDNA replication in Saccharomyces cerevisiae strains with disease-associated mutations affecting conserved regions of the mtDNA polymerase, Mip1, in the presence of the wild type Mip1. Mutant frequency arising from mtDNA base substitutions that confer erythromycin resistance and deletions between 21-nucleotide direct repeats was determined. Previously, increased mutagenesis was observed in strains encoding mutant variants that were insufficient to maintain mtDNA and that were not expected to reduce polymerase fidelity or exonuclease proofreading. Increased mutagenesis could be explained by mutant variants stalling the replication fork, thereby predisposing the template DNA to irreparable damage that is bypassed with poor fidelity. This hypothesis suggests that the exogenous base-alkylating agent, methyl methanesulfonate (MMS), would further increase mtDNA mutagenesis. Mitochondrial mutagenesis associated with MMS exposure was increased up to 30-fold in mip1 mutants containing disease-associated alterations that affect polymerase activity. Disrupting exonuclease activity of mutant variants was not associated with increased spontaneous mutagenesis compared with exonuclease-proficient alleles, suggesting that most or all of the mtDNA was replicated by wild type Mip1. A novel subset of C to G transversions was responsible for about half of the mutants arising after MMS exposure implicating error-prone bypass of methylated cytosines as the predominant mutational mechanism. Exposure to MMS does not disrupt exonuclease activity that suppresses deletions between 21-nucleotide direct repeats, suggesting the MMS-induce mutagenesis is not explained by inactivated exonuclease activity. Further, trace amounts of CdCl2 inhibit mtDNA replication but

  13. Genetic evidence for the proto-Austronesian homeland in Asia: mtDNA and nuclear DNA variation in Taiwanese aboriginal tribes.

    PubMed Central

    Melton, T; Clifford, S; Martinson, J; Batzer, M; Stoneking, M

    1998-01-01

    Previous studies of mtDNA variation in indigenous Taiwanese populations have suggested that they held an ancestral position in the spread of mtDNAs throughout Southeast Asia and Oceania (Melton et al. 1995; Sykes et al. 1995), but the question of an absolute proto-Austronesian homeland remains. To search for Asian roots for indigenous Taiwanese populations, 28 mtDNAs representative of variation in four tribal groups (Ami, Atayal, Bunun, and Paiwan) were sequenced and were compared with each other and with mtDNAs from 25 other populations from Asia and Oceania. In addition, eight polymorphic Alu insertion loci were analyzed, to determine if the pattern of mtDNA variation is concordant with nuclear DNA variation. Tribal groups shared considerable mtDNA sequence identity (P>.90), where gene flow is believed to have been low, arguing for a common source or sources for the tribes. mtDNAs with a 9-bp deletion have considerable mainland-Asian diversity and have spread to Southeast Asia and Oceania through a Taiwanese bottleneck. Only four Taiwanese mtDNA haplotypes without the 9-bp deletion were shared with any other populations, but these shared types were widely dispersed geographically throughout mainland Asia. Phylogenetic and principal-component analyses of Alu loci were concordant with conclusions from the mtDNA analyses; overall, the results suggest that the Taiwanese have temporally deep roots, probably in central or south China, and have been isolated from other Asian populations in recent history. PMID:9837834

  14. Congenital encephalomyopathy and adult-onset myopathy and diabetes mellitus: Different phenotypic associations of a new heteroplasmic mtDNA tRNA glutamic acid mutation

    SciTech Connect

    Hanna, M.G.; Nelson, I.; Sweeney, M.G.; Cooper, J.M.; Watkins, P.J.; Morgan-Hughes, J.A.; Harding, A.E.

    1995-05-01

    We report the clinical, biochemical, and molecular genetic findings in a family with an unusual mitochondrial disease phenotype harboring a novel mtDNA tRNA glutamic acid mutation at position 14709. The proband and his sister presented with congenital myopathy and mental retardation and subsequently developed cerebellar ataxia. Other family members had either adult-onset diabetes mellitus with muscle weakness or adult-onset diabetes mellitus alone. Ragged-red and cytochrome c oxidase (COX)-negative fibers were present in muscle biopsies. Biochemical studies of muscle mitochondria showed reduced complex I and IV activities. The mtDNA mutation was heteroplasmic in blood and muscle in all matrilineal relatives analyzed. Primary myoblast, but not fibroblast, cultures containing high proportions of mutant mtDNA exhibited impaired mitochondrial translation. These observations indicate that mtDNA tRNA point mutations should be considered in the differential diagnosis of congenital myopathy. In addition they illustrate the diversity of phenotypes associated with this mutation in the same family and further highlight the association between mtDNA mutations and diabetes mellitus. 43 refs., 4 figs., 1 tab.

  15. Complete nucleotide sequences of the domestic cat (Felis catus) mitochondrial genome and a transposed mtDNA tandem repeat (Numt) in the nuclear genome

    SciTech Connect

    Lopez, J.V.; Cevario, S.; O`Brien, S.J.

    1996-04-15

    The complete 17,009-bp mitochondrial genome of the domestic cat, Felis catus, has been sequenced and conforms largely to the typical organization of previously characterized mammalian mtDNAs. Codon usage and base composition also followed canonical vertebrate patterns, except for an unusual ATC (non-AUG) codon initiating the NADH dehydrogenase subunit 2 (ND2) gene. Two distinct repetitive motifs at opposite ends of the control region contribute to the relatively large size (1559 bp) of this carnivore mtDNA. Alignment of the feline mtDNA genome to a homologous 7946-bp nuclear mtDNA tandem repeat DNA sequence in the cat, Numt, indicates simple repeat motifs associated with insertion/deletion mutations. Overall DNA sequence divergence between Numt and cytoplasmic mtDNA sequence was only 5.1%. Substitutions predominate at the third codon position of homologous feline protein genes. Phylogenetic analysis of mitochondrial gene sequences confirms the recent transfer of the cytoplasmic mtDNA sequences to the domestic cat nucleus and recapitulates evolutionary relationships between mammal species. 86 refs., 4 figs., 3 tabs.

  16. Quantification of mtDNA in single oocytes, polar bodies and subcellular components by real-time rapid cycle fluorescence monitored PCR.

    PubMed

    Steuerwald, N; Barritt, J A; Adler, R; Malter, H; Schimmel, T; Cohen, J; Brenner, C A

    2000-08-01

    Oocytes, in general, are greatly enriched in mitochondria to support higher rates of macromolecular synthesis and critical physiological processes characteristic of early development. An inability of these organelles to amplify and/or to accumulate ATP has been linked to developmental abnormality or arrest. The number of mitochondrial genomes present in mature mouse and human metaphase II oocytes was estimated by fluorescent rapid cycle DNA amplification, which is a highly sensitive technique ideally suited to quantitative mitochondrial DNA (mtDNA) analysis in individual cells. A considerable degree of variability was observed between individual samples. An overall average of 1.59 x 10(5) and 3.14 x 10(5) mtDNA molecules were detected per mouse and human oocyte, respectively. Furthermore, the mtDNA copy number was examined in polar bodies and contrasted with the concentration in their corresponding oocytes. In addition, the density of mtDNA in a cytoplasmic sample was estimated in an attempt to determine the approximate number of mitochondria transferred during clinical cytoplasmic donation procedures as well as to develop a clinical tool for the assessment and selection of oocytes during in vitro fertilisation procedures. However, no correlation was identified between the mtDNA concentration in either polar bodies or cytoplasmic samples and their corresponding oocyte.

  17. Japanese Wolves are Genetically Divided into Two Groups Based on an 8-Nucleotide Insertion/Deletion within the mtDNA Control Region.

    PubMed

    Ishiguro, Naotaka; Inoshima, Yasuo; Yanai, Tokuma; Sasaki, Motoki; Matsui, Akira; Kikuchi, Hiroki; Maruyama, Masashi; Hongo, Hitomi; Vostretsov, Yuri E; Gasilin, Viatcheslav; Kosintsev, Pavel A; Quanjia, Chen; Chunxue, Wang

    2016-02-01

    The mitochondrial DNA (mtDNA) control region (198- to 598-bp) of four ancient Canis specimens (two Canis mandibles, a cranium, and a first phalanx) was examined, and each specimen was genetically identified as Japanese wolf. Two unique nucleotide substitutions, the 78-C insertion and the 482-G deletion, both of which are specific for Japanese wolf, were observed in each sample. Based on the mtDNA sequences analyzed, these four specimens and 10 additional Japanese wolf samples could be classified into two groups- Group A (10 samples) and Group B (4 samples)-which contain or lack an 8-bp insertion/deletion (indel), respectively. Interestingly, three dogs (Akita-b, Kishu 25, and S-husky 102) that each contained Japanese wolf-specific features were also classified into Group A or B based on the 8-bp indel. To determine the origin or ancestor of the Japanese wolf, mtDNA control regions of ancient continental Canis specimens were examined; 84 specimens were from Russia, and 29 were from China. However, none of these 113 specimens contained Japanese wolf-specific sequences. Moreover, none of 426 Japanese modern hunting dogs examined contained these Japanese wolf-specific mtDNA sequences. The mtDNA control region sequences of Groups A and B appeared to be unique to grey wolf and dog populations.

  18. Killer whale nuclear genome and mtDNA reveal widespread population bottleneck during the last glacial maximum.

    PubMed

    Moura, Andre E; Janse van Rensburg, Charlene; Pilot, Malgorzata; Tehrani, Arman; Best, Peter B; Thornton, Meredith; Plön, Stephanie; de Bruyn, P J Nico; Worley, Kim C; Gibbs, Richard A; Dahlheim, Marilyn E; Hoelzel, Alan Rus

    2014-05-01

    Ecosystem function and resilience is determined by the interactions and independent contributions of individual species. Apex predators play a disproportionately determinant role through their influence and dependence on the dynamics of prey species. Their demographic fluctuations are thus likely to reflect changes in their respective ecological communities and habitat. Here, we investigate the historical population dynamics of the killer whale based on draft nuclear genome data for the Northern Hemisphere and mtDNA data worldwide. We infer a relatively stable population size throughout most of the Pleistocene, followed by an order of magnitude decline and bottleneck during the Weichselian glacial period. Global mtDNA data indicate that while most populations declined, at least one population retained diversity in a stable, productive ecosystem off southern Africa. We conclude that environmental changes during the last glacial period promoted the decline of a top ocean predator, that these events contributed to the pattern of diversity among extant populations, and that the relatively high diversity of a population currently in productive, stable habitat off South Africa suggests a role for ocean productivity in the widespread decline.

  19. History of click-speaking populations of Africa inferred from mtDNA and Y chromosome genetic variation.

    PubMed

    Tishkoff, Sarah A; Gonder, Mary Katherine; Henn, Brenna M; Mortensen, Holly; Knight, Alec; Gignoux, Christopher; Fernandopulle, Neil; Lema, Godfrey; Nyambo, Thomas B; Ramakrishnan, Uma; Reed, Floyd A; Mountain, Joanna L

    2007-10-01

    Little is known about the history of click-speaking populations in Africa. Prior genetic studies revealed that the click-speaking Hadza of eastern Africa are as distantly related to click speakers of southern Africa as are most other African populations. The Sandawe, who currently live within 150 km of the Hadza, are the only other population in eastern Africa whose language has been classified as part of the Khoisan language family. Linguists disagree on whether there is any detectable relationship between the Hadza and Sandawe click languages. We characterized both mtDNA and Y chromosome variation of the Sandawe, Hadza, and neighboring Tanzanian populations. New genetic data show that the Sandawe and southern African click speakers share rare mtDNA and Y chromosome haplogroups; however, common ancestry of the 2 populations dates back >35,000 years. These data also indicate that common ancestry of the Hadza and Sandawe populations dates back >15,000 years. These findings suggest that at the time of the spread of agriculture and pastoralism, the click-speaking populations were already isolated from one another and are consistent with relatively deep linguistic divergence among the respective click languages.

  20. Genetic structure in Orchesella cincta (Collembola): strong subdivision of European populations inferred from mtDNA and AFLP markers.

    PubMed

    Timmermans, M J T N; Ellers, J; Mariën, J; Verhoef, S C; Ferwerda, E B; VAN Straalen, N M

    2005-06-01

    Population genetic structure is determined both by current processes and historical events. Current processes include gene flow, which is largely influenced by the migration capacity of a species. Historical events are, for example, glaciation periods, which have had a major impact on the distribution of many species. Species with a low capacity or tendency to move about or disperse often exhibit clear spatial genetic structures, whereas mobile species mostly show less spatial genetic differentiation. In this paper we report on the genetic structure of a small, wingless arthropod species (Orchesella cincta: Collembola) in Europe. For this purpose we used mtDNA COII sequences and AFLP markers. We show that large genetic differences exist between populations of O. cincta, as expected from O. cincta's winglessness and sedentary lifestyle. Despite the fact that most variability was observed within populations (59%), a highly significant amount of AFLP variation (25%) was observed between populations from northwestern Europe, central Europe and Italy. This suggests that gene flow among regions is extremely low, which is additionally supported by the lack of shared mtDNA alleles between regions. Based on the genetic variation and sequence differences observed we conclude that the subdivision occurred long before the last glaciation periods. Although the populations still interbreed in the lab, we assume that in the long term the genetic isolation of these regions may lead to speciation processes.

  1. Rapid proliferation of repetitive palindromic elements in mtDNA of the endemic Baikalian sponge Lubomirskia baicalensis.

    PubMed

    Lavrov, Dennis V

    2010-04-01

    Animal mitochondrial DNA (mtDNA) is a remarkably compact molecule largely because of the scarcity of noncoding "selfish" DNA. Recently, however, we found that mitochondrial genomes of several phylogenetically diverse species of demosponges contain small repetitive palindromic sequences, interspersed within intergenic regions and fused in protein and ribosomal RNA genes. Here, I report and analyze the proliferation of such elements in the mitochondrial genome of the endemic sponge of Lake Baikal Lubomirskia baicalensis. Because Baikal sponges are closely related to the circumglobally distributed freshwater sponge Ephydatia muelleri with which they shared a common ancestor approximately 3-10 Ma, both the rate of single nucleotide substitutions and the rate of palindromic repeat insertions can be calculated in this system. I found the rate of nucleotide substitutions in mtDNA of freshwater sponges to be extremely low (0.5-1.6 x 10(-9) per site per year), more similar to that in plants than bilaterian animals. By contrast, the per/nucleotide rate of insertions of repetitive elements is at least four times higher. This rapid rate of proliferation combined with the broad phylogenetic distribution of hairpin elements can make them a defining force in the evolution of mitochondrial genomes of demosponges.

  2. Analysis of mtDNA HVRII in several human populations using an immobilised SSO probe hybridisation assay.

    PubMed

    Comas, D; Reynolds, R; Sajantila, A

    1999-01-01

    Several populations were typed for the hypervariable region II (HVRII) of the mitochondrial DNA (mtDNA) control region using immobilised sequence-specific oligonucleotide (SSO) probes. A total of 16 SSO probes was used to type 1081 individuals from eight different ethnic groups (African Americans, Somali, US Europeans, US Hispanics, Bosnians, Finns, Saami and Japanese). Data was compared with already published sequence data by analysis of principal components, genetic distances and analysis of the molecular variance (AMOVA). The analyses performed group the samples in several clusters according to their geographical origins. Most of the variability detected is assigned to differences between individuals and only 7% is assigned to differences among groups of populations within and between geographical regions. Several features are patent in the samples studied: Somali, as a representative East African population, seem to have experienced a detectable amount of Caucasoid maternal influence; different degrees of admixture in the US samples studied are detected; Finns and Saami belong to the European genetic landscape, although Saami present an outlier position attributable to a strong maternal founder effect. The technique used is a rapid and simple method to detect human variation in the mtDNA HVRII in a large number of samples, which might be useful in forensic and population genetic studies.

  3. Feather barbs as a good source of mtDNA for bird species identification in forensic wildlife investigations

    PubMed Central

    2011-01-01

    Background The ability to accurately identify bird species is crucial for wildlife law enforcement and bird-strike investigations. However, such identifications may be challenging when only partial or damaged feathers are available for analysis. Results By applying vigorous contamination controls and sensitive PCR amplification protocols, we found that it was feasible to obtain accurate mitochondrial (mt)DNA-based species identification with as few as two feather barbs. This minimally destructive DNA approach was successfully used and tested on a variety of bird species, including North American wild turkey (Meleagris gallopavo), Canada goose (Branta canadensis), blue heron (Ardea herodias) and pygmy owl (Glaucidium californicum). The mtDNA was successfully obtained from 'fresh' feathers, historic museum specimens and archaeological samples, demonstrating the sensitivity and versatility of this technique. Conclusions By applying appropriate contamination controls, sufficient quantities of mtDNA can be reliably recovered and analyzed from feather barbs. This previously overlooked substrate provides new opportunities for accurate DNA species identification when minimal feather samples are available for forensic analysis. PMID:21794178

  4. High prevalence of non-synonymous substitutions in mtDNA of cichlid fishes from Lake Victoria.

    PubMed

    Shirai, Kazumasa; Inomata, Nobuyuki; Mizoiri, Shinji; Aibara, Mitsuto; Terai, Yohey; Okada, Norihiro; Tachida, Hidenori

    2014-12-01

    When a population size is reduced, genetic drift may fix slightly deleterious mutations, and an increase in nonsynonymous substitution is expected. It has been suggested that past aridity has seriously affected and decreased the populations of cichlid fishes in Lake Victoria, while geographical studies have shown that the water levels in Lake Tanganyika and Lake Malawi have remained fairly constant. The comparably stable environments in the latter two lakes might have kept the populations of cichlid fishes large enough to remove slightly deleterious mutations. The difference in the stability of cichlid fish population sizes between Lake Victoria and the Lakes Tanganyika and Malawi is expected to have caused differences in the nonsynonymous/synonymous ratio, ω (=dN/dS), of the evolutionary rate. Here, we estimated ω and compared it between the cichlids of the three lakes for 13 mitochondrial protein-coding genes using maximum likelihood methods. We found that the lineages of the cichlids in Lake Victoria had a significantly higher ω for several mitochondrial loci. Moreover, positive selection was indicated for several codons in the mtDNA of the Lake Victoria cichlid lineage. Our results indicate that both adaptive and slightly deleterious molecular evolution has taken place in the Lake Victoria cichlids' mtDNA genes, whose nonsynonymous sites are generally conserved.

  5. More reliable estimates of divergence times in Pan using complete mtDNA sequences and accounting for population structure.

    PubMed

    Stone, Anne C; Battistuzzi, Fabia U; Kubatko, Laura S; Perry, George H; Trudeau, Evan; Lin, Hsiuman; Kumar, Sudhir

    2010-10-27

    Here, we report the sequencing and analysis of eight complete mitochondrial genomes of chimpanzees (Pan troglodytes) from each of the three established subspecies (P. t. troglodytes, P. t. schweinfurthii and P. t. verus) and the proposed fourth subspecies (P. t. ellioti). Our population genetic analyses are consistent with neutral patterns of evolution that have been shaped by demography. The high levels of mtDNA diversity in western chimpanzees are unlike those seen at nuclear loci, which may reflect a demographic history of greater female to male effective population sizes possibly owing to the characteristics of the founding population. By using relaxed-clock methods, we have inferred a timetree of chimpanzee species and subspecies. The absolute divergence times vary based on the methods and calibration used, but relative divergence times show extensive uniformity. Overall, mtDNA produces consistently older times than those known from nuclear markers, a discrepancy that is reduced significantly by explicitly accounting for chimpanzee population structures in time estimation. Assuming the human-chimpanzee split to be between 7 and 5 Ma, chimpanzee time estimates are 2.1-1.5, 1.1-0.76 and 0.25-0.18 Ma for the chimpanzee/bonobo, western/(eastern + central) and eastern/central chimpanzee divergences, respectively.

  6. Eight new mtDNA sequences of glass sponges reveal an extensive usage of +1 frameshifting in mitochondrial translation.

    PubMed

    Haen, Karri M; Pett, Walker; Lavrov, Dennis V

    2014-02-10

    Three previously studied mitochondrial genomes of glass sponges (phylum Porifera, class Hexactinellida) contained single nucleotide insertions in protein coding genes inferred as sites of +1 translational frameshifting. To investigate the distribution and evolution of these sites and to help elucidate the mechanism of frameshifting, we determined eight new complete or nearly complete mtDNA sequences from glass sponges and examined individual mitochondrial genes from three others. We found nine new instances of single nucleotide insertions in these sequences and analyzed them both comparatively and phylogenetically. The base insertions appear to have been gained and lost repeatedly in hexactinellid mt protein genes, suggesting no functional significance for the frameshifting sites. A high degree of sequence conservation, the presence of unusual tRNAs, and a distinct pattern of codon usage suggest the "out-of-frame pairing" model of translational frameshifting. Additionally, we provide evidence that relaxed selection pressure on glass sponge mtDNA - possibly a result of their low growth rates and deep-water lifestyle - has allowed frameshift insertions to be tolerated for hundreds of millions of years. Our study provides the first example of a phylogenetically diverse and extensive usage of translational frameshifting in animal mitochondrial coding sequences.

  7. Monomelic amyotrophy associated with the 7472insC mutation in the mtDNA tRNASer(UCN) gene.

    PubMed

    Fetoni, Vincenza; Briem, Egill; Carrara, Franco; Mora, Marina; Zeviani, Massimo

    2004-11-01

    We describe a 49-year-old male patient who experienced progressive amyotrophy with no sensorial abnormality in the left arm since 45 years of age. The neuromuscular syndrome was identical to that known as Hirayama disease, a rare form of focal lower motor neuron disease affecting the C7-C8-T1 metamers of the spinal cord. Asymmetric neurosensorial hearing loss was present since age 35 in the patient, and was also documented in an elder sister and in the mother. A muscle biopsy showed cytochrome c oxidase (COX) negative fibers but no ragged-red fibers, and mild reduction of COX was confirmed biochemically. The patient was found to have high levels of a known pathogenic mutation of mtDNA, the 7472insC in the gene encoding the tRNA(Ser(UCN)). Investigation on several family members showed a correlation between mutation load and clinical severity. This is the second report documenting the association of lower motor neurone involvement with a specific mtDNA.

  8. Generation of trans-mitochondrial mito-mice by the introduction of a pathogenic G13997A mtDNA from highly metastatic lung carcinoma cells.

    PubMed

    Yokota, Mutsumi; Shitara, Hiroshi; Hashizume, Osamu; Ishikawa, Kaori; Nakada, Kazuto; Ishii, Rie; Taya, Choji; Takenaga, Keizo; Yonekawa, Hiromichi; Hayashi, Jun-Ichi

    2010-09-24

    To investigate the effects of respiration defects on the disease phenotypes, we generated trans-mitochondrial mice (mito-mice) by introducing a mutated G13997A mtDNA, which specifically induces respiratory complex I defects and metastatic potentials in mouse tumor cells. First, we obtained ES cells and chimeric mice containing the G13997A mtDNA, and then we generated mito-mice carrying the G13997A mtDNA via its female germ line transmission. The three-month-old mito-mice showed complex I defects and lactate overproduction, but showed no other phenotypes related to mitochondrial diseases or tumor formation, suggesting that aging or additional nuclear abnormalities are required for expression of other phenotypes.

  9. Transmission of human mtDNA heteroplasmy in the Genome of the Netherlands families: support for a variable-size bottleneck

    PubMed Central

    Li, Mingkun; Rothwell, Rebecca; Vermaat, Martijn; Wachsmuth, Manja; Schröder, Roland; Laros, Jeroen F.J.; van Oven, Mannis; de Bakker, Paul I.W.; Bovenberg, Jasper A.; van Duijn, Cornelia M.; van Ommen, Gert-Jan B.; Slagboom, P. Eline; Swertz, Morris A.; Wijmenga, Cisca; Kayser, Manfred; Boomsma, Dorret I.; Zöllner, Sebastian; de Knijff, Peter; Stoneking, Mark

    2016-01-01

    Although previous studies have documented a bottleneck in the transmission of mtDNA genomes from mothers to offspring, several aspects remain unclear, including the size and nature of the bottleneck. Here, we analyze the dynamics of mtDNA heteroplasmy transmission in the Genomes of the Netherlands (GoNL) data, which consists of complete mtDNA genome sequences from 228 trios, eight dizygotic (DZ) twin quartets, and 10 monozygotic (MZ) twin quartets. Using a minor allele frequency (MAF) threshold of 2%, we identified 189 heteroplasmies in the trio mothers, of which 59% were transmitted to offspring, and 159 heteroplasmies in the trio offspring, of which 70% were inherited from the mothers. MZ twin pairs exhibited greater similarity in MAF at heteroplasmic sites than DZ twin pairs, suggesting that the heteroplasmy MAF in the oocyte is the major determinant of the heteroplasmy MAF in the offspring. We used a likelihood method to estimate the effective number of mtDNA genomes transmitted to offspring under different bottleneck models; a variable bottleneck size model provided the best fit to the data, with an estimated mean of nine individual mtDNA genomes transmitted. We also found evidence for negative selection during transmission against novel heteroplasmies (in which the minor allele has never been observed in polymorphism data). These novel heteroplasmies are enhanced for tRNA and rRNA genes, and mutations associated with mtDNA diseases frequently occur in these genes. Our results thus suggest that the female germ line is able to recognize and select against deleterious heteroplasmies. PMID:26916109

  10. Mitochondrial DNA (mtDNA) variants in the European haplogroups HV, JT, and U do not have a major role in schizophrenia.

    PubMed

    Torrell, Helena; Salas, Antonio; Abasolo, Nerea; Morén, Constanza; Garrabou, Glòria; Valero, Joaquín; Alonso, Yolanda; Vilella, Elisabet; Costas, Javier; Martorell, Lourdes

    2014-10-01

    It has been reported that certain genetic factors involved in schizophrenia could be located in the mitochondrial DNA (mtDNA). Therefore, we hypothesized that mtDNA mutations and/or variants would be present in schizophrenia patients and may be related to schizophrenia characteristics and mitochondrial function. This study was performed in three steps: (1) identification of pathogenic mutations and variants in 14 schizophrenia patients with an apparent maternal inheritance of the disease by sequencing the entire mtDNA; (2) case-control association study of 23 variants identified in step 1 (16 missense, 3 rRNA, and 4 tRNA variants) in 495 patients and 615 controls, and (3) analyses of the associated variants according to the clinical, psychopathological, and neuropsychological characteristics and according to the oxidative and enzymatic activities of the mitochondrial respiratory chain. We did not identify pathogenic mtDNA mutations in the 14 sequenced patients. Two known variants were nominally associated with schizophrenia and were further studied. The MT-RNR2 1811A > G variant likely does not play a major role in schizophrenia, as it was not associated with clinical, psychopathological, or neuropsychological variables, and the MT-ATP6 9110T > C p.Ile195Thr variant did not result in differences in the oxidative and enzymatic functions of the mitochondrial respiratory chain. The patients with apparent maternal inheritance of schizophrenia did not exhibit any mutations in their mtDNA. The variants nominally associated with schizophrenia in the present study were not related either to phenotypic characteristics or to mitochondrial function. We did not find evidence pointing to a role for mtDNA sequence variation in schizophrenia.

  11. Molecular phylogeny of grey mullets (Teleostei: Mugilidae) in Greece: evidence from sequence analysis of mtDNA segments.

    PubMed

    Papasotiropoulos, Vasilis; Klossa-Kilia, Elena; Alahiotis, Stamatis N; Kilias, George

    2007-08-01

    Mitochondrial DNA sequence analysis has been used to explore genetic differentiation and phylogenetic relationships among five species of the Mugilidae family, Mugil cephalus, Chelon labrosus, Liza aurata, Liza ramada, and Liza saliens. DNA was isolated from samples originating from the Messolongi Lagoon in Greece. Three mtDNA segments (12s rRNA, 16s rRNA, and CO I) were PCR amplified and sequenced. Sequencing analysis revealed that the greatest genetic differentiation was observed between M. cephalus and all the other species studied, while C. labrosus and L. aurata were the closest taxa. Dendrograms obtained by the neighbor-joining method and Bayesian inference analysis exhibited the same topology. According to this topology, M. cephalus is the most distinct species and the remaining taxa are clustered together, with C. labrosus and L. aurata forming a single group. The latter result brings into question the monophyletic origin of the genus Liza.

  12. Pursuing the quest for better understanding the taxonomic distribution of the system of doubly uniparental inheritance of mtDNA

    PubMed Central

    Gusman, Arthur; Lecomte, Sophia; Stewart, Donald T.; Passamonti, Marco

    2016-01-01

    There is only one exception to strict maternal inheritance of mitochondrial DNA (mtDNA) in the animal kingdom: a system named doubly uniparental inheritance (DUI), which is found in several bivalve species. Why and how such a radically different system of mitochondrial transmission evolved in bivalve remains obscure. Obtaining a more complete taxonomic distribution of DUI in the Bivalvia may help to better understand its origin and function. In this study we provide evidence for the presence of sex-linked heteroplasmy (thus the possible presence of DUI) in two bivalve species, i.e., the nuculanoid Yoldia hyperborea(Gould, 1841)and the veneroid Scrobicularia plana(Da Costa,1778), increasing the number of families in which DUI has been found by two. An update on the taxonomic distribution of DUI in the Bivalvia is also presented. PMID:27994972

  13. Personal identification of cold case remains through combined contribution from anthropological, mtDNA, and bomb-pulse dating analyses.

    PubMed

    Speller, Camilla F; Spalding, Kirsty L; Buchholz, Bruce A; Hildebrand, Dean; Moore, Jason; Mathewes, Rolf; Skinner, Mark F; Yang, Dongya Y

    2012-09-01

    In 1968, a child's cranium was recovered from the banks of a northern Canadian river and held in a trust until the "cold case" was reopened in 2005. The cranium underwent reanalysis at the Centre for Forensic Research, Simon Fraser University, using recently developed anthropological analysis, "bomb-pulse" radiocarbon analysis, and forensic DNA techniques. Craniometrics, skeletal ossification, and dental formation indicated an age-at-death of 4.4 ± 1 year. Radiocarbon analysis of enamel from two teeth indicated a year of birth between 1958 and 1962. Forensic DNA analysis indicated the child was a male, and the obtained mitochondrial profile matched a living maternal relative to the presumed missing child. These multidisciplinary analyses resulted in a legal identification 41 years after the discovery of the remains, highlighting the enormous potential of combining radiocarbon analysis with anthropological and mtDNA analyses in producing confident personal identifications for forensic cold cases dating to within the last 60 years.

  14. Mixed-stock analysis in green turtles Chelonia mydas: mtDNA decipher current connections among west Atlantic populations.

    PubMed

    Costa Jordao, Juliana; Bondioli, Ana Cristina Vigliar; Almeida-Toledo, Lurdes Foresti de; Bilo, Karin; Berzins, Rachel; Le Maho, Yvon; Chevallier, Damien; de Thoisy, Benoit

    2017-03-01

    The green turtle Chelonia mydas undertakes wide-ranging migrations between feeding and nesting sites, resulting in mixing and isolation of genetic stocks. We used mtDNA control region to characterize the genetic composition, population structure, and natal origins of C. mydas in the West Atlantic Ocean, at one feeding ground (State of Rio de Janeiro, Brazil), and three Caribbean nesting grounds (French Guiana, Guadeloupe, and Suriname). The feeding ground presented considerable frequency of common haplotypes from the South Atlantic, whereas the nesting sites presented a major contribution of the most common haplotype from the Caribbean. MSA revealed multiple origins of individuals at the feeding ground, notably from Ascension Island, Guinea Bissau, and French Guiana. This study enables a better understanding of the dispersion patterns and highlights the importance of connecting both nesting and feeding areas. Effective conservation initiatives need to encompass these ecologically and geographically distinct sites as well as those corridors connecting them.

  15. Phylogeography of the rice frog, Fejervarya multistriata (Anura: Ranidae), from China based on mtDNA D-loop sequences.

    PubMed

    Zhong, Jing; Liu, Zhong-Quan; Wang, Yi-Quan

    2008-08-01

    The rice frog, Fejervarya multistriata, is an amphibian widely distributed in China. In this study, we sampled the species across its distributional area in China and sequenced the mtDNA D-loop to investigate the genetic diversity and geographical pattern of the frog population. The results revealed 38 haplotypes in the population, with K2P values varying from 0.19% to 4.22%. Both a phylogenetic analysis and a nested clade analysis (NCA) detected two geographically isolated lineages respectively distributed around the Yangtze drainage (Yangtze lineage) and the south of China (southern lineage). NCA inferred a contiguous range expansion within the Yangtze lineage and allopatric fragmentation within the southern lineage, which might be partly due to the limited samples from this lineage. Accordingly, Fu's Fs test also indicated a population expansion after glacial movement. Therefore, we assumed that the species history responding to glacial events shaped the present population pattern of F. multistriata on the Chinese mainland.

  16. Pursuing the quest for better understanding the taxonomic distribution of the system of doubly uniparental inheritance of mtDNA.

    PubMed

    Gusman, Arthur; Lecomte, Sophia; Stewart, Donald T; Passamonti, Marco; Breton, Sophie

    2016-01-01

    There is only one exception to strict maternal inheritance of mitochondrial DNA (mtDNA) in the animal kingdom: a system named doubly uniparental inheritance (DUI), which is found in several bivalve species. Why and how such a radically different system of mitochondrial transmission evolved in bivalve remains obscure. Obtaining a more complete taxonomic distribution of DUI in the Bivalvia may help to better understand its origin and function. In this study we provide evidence for the presence of sex-linked heteroplasmy (thus the possible presence of DUI) in two bivalve species, i.e., the nuculanoid Yoldia hyperborea(Gould, 1841)and the veneroid Scrobicularia plana(Da Costa,1778), increasing the number of families in which DUI has been found by two. An update on the taxonomic distribution of DUI in the Bivalvia is also presented.

  17. Strict sex-specific mtDNA segregation in the germ line of the DUI species Venerupis philippinarum (Bivalvia: Veneridae).

    PubMed

    Ghiselli, Fabrizio; Milani, Liliana; Passamonti, Marco

    2011-02-01

    Doubly Uniparental Inheritance (DUI) is one of the most striking exceptions to the common rule of standard maternal inheritance of metazoan mitochondria. In DUI, two mitochondrial genomes are present, showing different transmission routes, one through eggs (F-type) and the other through sperm (M-type). In this paper, we report results from a multiplex real-time quantitative polymerase chain reaction analysis on the Manila clam Venerupis philippinarum (formerly Tapes philippinarum). We quantified M- and F-types in somatic tissues, gonads, and gametes. Nuclear and external reference sequences were used, and the whole experimental process was designed to avoid any possible cross-contamination. In most male somatic tissues, the M-type is largely predominant: This suggests that the processes separating sex-linked mitochondrial DNAs (mtDNAs) in somatic tissues are less precise than in other DUI species. In the germ line, we evidenced a strict sex-specific mtDNA segregation because both sperm and eggs do carry exclusively M- and F-types, respectively, an observation that is in contrast with a previous analysis on Mytilus galloprovincialis. More precisely, whereas two mtDNAs are present in the whole gonad, only the sex-specific one is detected in gametes. Because of this, we propose that the mtDNA transmission is achieved through a three-checkpoint process in V. philippinarum. The cytological mechanisms of male mitochondria segregation in males and degradation in females during the embryo development (here named Checkpoint #1 and Checkpoint #2) are already well known for DUI species; a Checkpoint #3 would act when primordial germ cells (PGCs) are first formed and would work in both males and females. We believe that Checkpoint #3 is a mere variation of the "mitochondrial bottleneck" in species with standard maternal inheritance, established when their PGCs separate during embryo cleavage.

  18. Migration and interaction in a contact zone: mtDNA variation among Bantu-speakers in Southern Africa.

    PubMed

    Barbieri, Chiara; Vicente, Mário; Oliveira, Sandra; Bostoen, Koen; Rocha, Jorge; Stoneking, Mark; Pakendorf, Brigitte

    2014-01-01

    Bantu speech communities expanded over large parts of sub-Saharan Africa within the last 4000-5000 years, reaching different parts of southern Africa 1200-2000 years ago. The Bantu languages subdivide in several major branches, with languages belonging to the Eastern and Western Bantu branches spreading over large parts of Central, Eastern, and Southern Africa. There is still debate whether this linguistic divide is correlated with a genetic distinction between Eastern and Western Bantu speakers. During their expansion, Bantu speakers would have come into contact with diverse local populations, such as the Khoisan hunter-gatherers and pastoralists of southern Africa, with whom they may have intermarried. In this study, we analyze complete mtDNA genome sequences from over 900 Bantu-speaking individuals from Angola, Zambia, Namibia, and Botswana to investigate the demographic processes at play during the last stages of the Bantu expansion. Our results show that most of these Bantu-speaking populations are genetically very homogenous, with no genetic division between speakers of Eastern and Western Bantu languages. Most of the mtDNA diversity in our dataset is due to different degrees of admixture with autochthonous populations. Only the pastoralist Himba and Herero stand out due to high frequencies of particular L3f and L3d lineages; the latter are also found in the neighboring Damara, who speak a Khoisan language and were foragers and small-stock herders. In contrast, the close cultural and linguistic relatives of the Herero and Himba, the Kuvale, are genetically similar to other Bantu-speakers. Nevertheless, as demonstrated by resampling tests, the genetic divergence of Herero, Himba, and Kuvale is compatible with a common shared ancestry with high levels of drift, while the similarity of the Herero, Himba, and Damara probably reflects admixture, as also suggested by linguistic analyses.

  19. Early Holocenic and Historic mtDNA African Signatures in the Iberian Peninsula: The Andalusian Region as a Paradigm.

    PubMed

    Hernández, Candela L; Soares, Pedro; Dugoujon, Jean M; Novelletto, Andrea; Rodríguez, Juan N; Rito, Teresa; Oliveira, Marisa; Melhaoui, Mohammed; Baali, Abdellatif; Pereira, Luisa; Calderón, Rosario

    2015-01-01

    Determining the timing, identity and direction of migrations in the Mediterranean Basin, the role of "migratory routes" in and among regions of Africa, Europe and Asia, and the effects of sex-specific behaviors of population movements have important implications for our understanding of the present human genetic diversity. A crucial component of the Mediterranean world is its westernmost region. Clear features of transcontinental ancient contacts between North African and Iberian populations surrounding the maritime region of Gibraltar Strait have been identified from archeological data. The attempt to discern origin and dates of migration between close geographically related regions has been a challenge in the field of uniparental-based population genetics. Mitochondrial DNA (mtDNA) studies have been focused on surveying the H1, H3 and V lineages when trying to ascertain north-south migrations, and U6 and L in the opposite direction, assuming that those lineages are good proxies for the ancestry of each side of the Mediterranean. To this end, in the present work we have screened entire mtDNA sequences belonging to U6, M1 and L haplogroups in Andalusians--from Huelva and Granada provinces--and Moroccan Berbers. We present here pioneer data and interpretations on the role of NW Africa and the Iberian Peninsula regarding the time of origin, number of founders and expansion directions of these specific markers. The estimated entrance of the North African U6 lineages into Iberia at 10 ky correlates well with other L African clades, indicating that U6 and some L lineages moved together from Africa to Iberia in the Early Holocene. Still, founder analysis highlights that the high sharing of lineages between North Africa and Iberia results from a complex process continued through time, impairing simplistic interpretations. In particular, our work supports the existence of an ancient, frequently denied, bridge connecting the Maghreb and Andalusia.

  20. Minding the gap: Frequency of indels in mtDNA control region sequence data and influence on population genetic analyses

    USGS Publications Warehouse

    Pearce, J.M.

    2006-01-01

    Insertions and deletions (indels) result in sequences of various lengths when homologous gene regions are compared among individuals or species. Although indels are typically phylogenetically informative, occurrence and incorporation of these characters as gaps in intraspecific population genetic data sets are rarely discussed. Moreover, the impact of gaps on estimates of fixation indices, such as FST, has not been reviewed. Here, I summarize the occurrence and population genetic signal of indels among 60 published studies that involved alignments of multiple sequences from the mitochondrial DNA (mtDNA) control region of vertebrate taxa. Among 30 studies observing indels, an average of 12% of both variable and parsimony-informative sites were composed of these sites. There was no consistent trend between levels of population differentiation and the number of gap characters in a data block. Across all studies, the average influence on estimates of ??ST was small, explaining only an additional 1.8% of among population variance (range 0.0-8.0%). Studies most likely to observe an increase in ??ST with the inclusion of gap characters were those with < 20 variable sites, but a near equal number of studies with few variable sites did not show an increase. In contrast to studies at interspecific levels, the influence of indels for intraspecific population genetic analyses of control region DNA appears small, dependent upon total number of variable sites in the data block, and related to species-specific characteristics and the spatial distribution of mtDNA lineages that contain indels. ?? 2006 Blackwell Publishing Ltd.

  1. Early Holocenic and Historic mtDNA African Signatures in the Iberian Peninsula: The Andalusian Region as a Paradigm

    PubMed Central

    Hernández, Candela L.; Soares, Pedro; Dugoujon, Jean M.; Novelletto, Andrea; Rodríguez, Juan N.; Rito, Teresa; Oliveira, Marisa; Melhaoui, Mohammed; Baali, Abdellatif; Pereira, Luisa; Calderón, Rosario

    2015-01-01

    Determining the timing, identity and direction of migrations in the Mediterranean Basin, the role of “migratory routes” in and among regions of Africa, Europe and Asia, and the effects of sex-specific behaviors of population movements have important implications for our understanding of the present human genetic diversity. A crucial component of the Mediterranean world is its westernmost region. Clear features of transcontinental ancient contacts between North African and Iberian populations surrounding the maritime region of Gibraltar Strait have been identified from archeological data. The attempt to discern origin and dates of migration between close geographically related regions has been a challenge in the field of uniparental-based population genetics. Mitochondrial DNA (mtDNA) studies have been focused on surveying the H1, H3 and V lineages when trying to ascertain north-south migrations, and U6 and L in the opposite direction, assuming that those lineages are good proxies for the ancestry of each side of the Mediterranean. To this end, in the present work we have screened entire mtDNA sequences belonging to U6, M1 and L haplogroups in Andalusians—from Huelva and Granada provinces—and Moroccan Berbers. We present here pioneer data and interpretations on the role of NW Africa and the Iberian Peninsula regarding the time of origin, number of founders and expansion directions of these specific markers. The estimated entrance of the North African U6 lineages into Iberia at 10 ky correlates well with other L African clades, indicating that U6 and some L lineages moved together from Africa to Iberia in the Early Holocene. Still, founder analysis highlights that the high sharing of lineages between North Africa and Iberia results from a complex process continued through time, impairing simplistic interpretations. In particular, our work supports the existence of an ancient, frequently denied, bridge connecting the Maghreb and Andalusia. PMID:26509580

  2. European Y-chromosomal lineages in Polynesians: a contrast to the population structure revealed by mtDNA.

    PubMed Central

    Hurles, M E; Irven, C; Nicholson, J; Taylor, P G; Santos, F R; Loughlin, J; Jobling, M A; Sykes, B C

    1998-01-01

    We have used Y-chromosomal polymorphisms to trace paternal lineages in Polynesians by use of samples previously typed for mtDNA variants. A genealogical approach utilizing hierarchical analysis of eight rare-event biallelic polymorphisms, seven microsatellite loci, and internal structural analysis of the hypervariable minisatellite, MSY1, has been used to define three major paternal-lineage clusters in Polynesians. Two of these clusters, both defined by novel MSY1 modular structures and representing 55% of the Polynesians studied, are also found in coastal Papua New Guinea. Reduced Polynesian diversity, relative to that in Melanesians, is illustrated by the presence of several examples of identical MSY1 codes and microsatellite haplotypes within these lineage clusters in Polynesians. The complete lack of Y chromosomes having the M4 base substitution in Polynesians, despite their prevalence (64%) in Melanesians, may also be a result of the multiple bottleneck events during the colonization of this region of the world. The origin of the M4 mutation has been dated by use of two independent methods based on microsatellite-haplotype and minisatellite-code diversity. Because of the wide confidence limits on the mutation rates of these loci, the M4 mutation cannot be conclusively dated relative to the colonization of Polynesia, 3,000 years ago. The other major lineage cluster found in Polynesians, defined by a base substitution at the 92R7 locus, represents 27% of the Polynesians studied and, most probably, originates in Europe. This is the first Y-chromosomal evidence of major European admixture with indigenous Polynesian populations and contrasts sharply with the picture given by mtDNA evidence. PMID:9837833

  3. Somatic Point Mutations in mtDNA Control Region Are Influenced by Genetic Background and Associated with Healthy Aging: A GEHA Study

    PubMed Central

    Rose, Giuseppina; Romeo, Giuseppe; Dato, Serena; Crocco, Paolina; Bruni, Amalia C.; Hervonen, Antti; Majamaa, Kari; Sevini, Federica; Franceschi, Claudio; Passarino, Giuseppe

    2010-01-01

    Tissue specific somatic mutations occurring in the mtDNA control region have been proposed to provide a survival advantage. Data on twins and on relatives of long-lived subjects suggested that the occurrence/accumulation of these mutations may be genetically influenced. To further investigate control region somatic heteroplasmy in the elderly, we analyzed the segment surrounding the nt 150 position (previously reported as specific of Leukocytes) in various types of leukocytes obtained from 195 ultra-nonagenarians sib-pairs of Italian or Finnish origin collected in the frame of the GEHA Project. We found a significant correlation of the mtDNA control region heteroplasmy between sibs, confirming a genetic influence on this phenomenon. Furthermore, many subjects showed heteroplasmy due to mutations different from the C150T transition. In these cases heteroplasmy was correlated within sibpairs in Finnish and northern Italian samples, but not in southern Italians. This suggested that the genetic contribution to control region mutations may be population specific. Finally, we observed a possible correlation between heteroplasmy and Hand Grip strength, one of the best markers of physical performance and of mortality risk in the elderly. Our study provides new evidence on the relevance of mtDNA somatic mutations in aging and longevity and confirms that the occurrence of specific point mutations in the mtDNA control region may represent a strategy for the age-related remodelling of organismal functions. PMID:20976236

  4. Complete mtDNA sequences of two millipedes suggest a new model for mitochondrial gene rearrangements: Duplication and non-random loss

    SciTech Connect

    Lavrov, Dennis V.; Boore, Jeffrey L.; Brown, Wesley M.

    2001-11-08

    We determined the complete mtDNA sequences of the millipedes Narceus annularus and Thyropygus sp. (Arthropoda: Diplopoda) and identified in both genomes all 37 genes typical for metazoan mtDNA. The arrangement of these genes is identical in the two millipedes, but differs from that inferred to be ancestral for arthropods by the location of four genes/gene clusters. This novel gene arrangement is unusual for animal mtDNA, in that genes with opposite transcriptional polarities are clustered in the genome and the two clusters are separated by two non-coding regions. The only exception to this pattern is the gene for cysteine tRNA, which is located in the part of the genome that otherwise contains all genes with the opposite transcriptional polarity. We suggest that a mechanism involving complete mtDNA duplication followed by the loss of genes, predetermined by their transcriptional polarity and location in the genome, could generate this gene arrangement from the one ancestral for arthropods. The proposed mechanism has important implications for phylogenetic inferences that are drawn on the basis of gene arrangement comparisons.

  5. GENETIC STRUCTURE OF CREEK CHUB (SEMOTILUS ATROMACULATUS) POPULATIONS IN COAL MINING-IMPACTED AREAS OF THE EASTERN UNITED STATES, AS DETERMINED BY MTDNA SEQUENCING AND AFLP ANALYSIS

    EPA Science Inventory

    Analysis of intraspecific patterns in genetic diversity of stream fishes provides a potentially powerful method for assessing the status and trends in the condition of aquatic ecosystems. We analyzed mitochondrial DNA (mtDNA) sequences (590 bases of cytochrome B) and nuclear DNA...

  6. The co-occurrence of mtDNA mutations on different oxidative phosphorylation subunits, not detected by haplogroup analysis, affects human longevity and is population specific.

    PubMed

    Raule, Nicola; Sevini, Federica; Li, Shengting; Barbieri, Annalaura; Tallaro, Federica; Lomartire, Laura; Vianello, Dario; Montesanto, Alberto; Moilanen, Jukka S; Bezrukov, Vladyslav; Blanché, Hélène; Hervonen, Antti; Christensen, Kaare; Deiana, Luca; Gonos, Efstathios S; Kirkwood, Tom B L; Kristensen, Peter; Leon, Alberta; Pelicci, Pier Giuseppe; Poulain, Michel; Rea, Irene M; Remacle, Josè; Robine, Jean Marie; Schreiber, Stefan; Sikora, Ewa; Eline Slagboom, Peternella; Spazzafumo, Liana; Antonietta Stazi, Maria; Toussaint, Olivier; Vaupel, James W; Rose, Giuseppina; Majamaa, Kari; Perola, Markus; Johnson, Thomas E; Bolund, Lars; Yang, Huanming; Passarino, Giuseppe; Franceschi, Claudio

    2014-06-01

    To re-examine the correlation between mtDNA variability and longevity, we examined mtDNAs from samples obtained from over 2200 ultranonagenarians (and an equal number of controls) collected within the framework of the GEHA EU project. The samples were categorized by high-resolution classification, while about 1300 mtDNA molecules (650 ultranonagenarians and an equal number of controls) were completely sequenced. Sequences, unlike standard haplogroup analysis, made possible to evaluate for the first time the cumulative effects of specific, concomitant mtDNA mutations, including those that per se have a low, or very low, impact. In particular, the analysis of the mutations occurring in different OXPHOS complex showed a complex scenario with a different mutation burden in 90+ subjects with respect to controls. These findings suggested that mutations in subunits of the OXPHOS complex I had a beneficial effect on longevity, while the simultaneous presence of mutations in complex I and III (which also occurs in J subhaplogroups involved in LHON) and in complex I and V seemed to be detrimental, likely explaining previous contradictory results. On the whole, our study, which goes beyond haplogroup analysis, suggests that mitochondrial DNA variation does affect human longevity, but its effect is heavily influenced by the interaction between mutations concomitantly occurring on different mtDNA genes.

  7. Abnormally activated one-carbon metabolic pathway is associated with mtDNA hypermethylation and mitochondrial malfunction in the oocytes of polycystic gilt ovaries

    PubMed Central

    Jia, Longfei; Li, Juan; He, Bin; Jia, Yimin; Niu, Yingjie; Wang, Chenfei; Zhao, Ruqian

    2016-01-01

    Polycystic ovarian syndrome (PCOS) is associated with hyperhomocysteinemia and polycystic ovaries (PCO) usually produce oocytes of poor quality. However, the intracellular mechanism linking hyperhomocysteinemia and oocyte quality remains elusive. In this study, the quality of the oocytes isolated from healthy and polycystic gilt ovaries was evaluated in vitro in association with one-carbon metabolism, mitochondrial DNA (mtDNA) methylation, and mitochondrial function. PCO oocytes demonstrated impaired polar body extrusion, and significantly decreased cleavage and blastocyst rates. The mitochondrial distribution was disrupted in PCO oocytes, together with decreased mitochondrial membrane potential and deformed mitochondrial structure. The mtDNA copy number and the expression of mtDNA-encoded genes were significantly lower in PCO oocytes. Homocysteine concentration in follicular fluid was significantly higher in PCO group, which was associated with significantly up-regulated one-carbon metabolic enzymes betaine homocysteine methyltransferase (BHMT), glycine N-methyltransferase (GNMT) and the DNA methyltransferase DNMT1. Moreover, mtDNA sequences coding for 12S, 16S rRNA and ND4, as well as the D-loop region were significantly hypermethylated in PCO oocytes. These results indicate that an abnormal activation of one-carbon metabolism and hypermethylation of mtDNA may contribute, largely, to the mitochondrial malfunction and decreased quality of PCO-derived oocytes in gilts. PMID:26758245

  8. Abnormally activated one-carbon metabolic pathway is associated with mtDNA hypermethylation and mitochondrial malfunction in the oocytes of polycystic gilt ovaries.

    PubMed

    Jia, Longfei; Li, Juan; He, Bin; Jia, Yimin; Niu, Yingjie; Wang, Chenfei; Zhao, Ruqian

    2016-01-13

    Polycystic ovarian syndrome (PCOS) is associated with hyperhomocysteinemia and polycystic ovaries (PCO) usually produce oocytes of poor quality. However, the intracellular mechanism linking hyperhomocysteinemia and oocyte quality remains elusive. In this study, the quality of the oocytes isolated from healthy and polycystic gilt ovaries was evaluated in vitro in association with one-carbon metabolism, mitochondrial DNA (mtDNA) methylation, and mitochondrial function. PCO oocytes demonstrated impaired polar body extrusion, and significantly decreased cleavage and blastocyst rates. The mitochondrial distribution was disrupted in PCO oocytes, together with decreased mitochondrial membrane potential and deformed mitochondrial structure. The mtDNA copy number and the expression of mtDNA-encoded genes were significantly lower in PCO oocytes. Homocysteine concentration in follicular fluid was significantly higher in PCO group, which was associated with significantly up-regulated one-carbon metabolic enzymes betaine homocysteine methyltransferase (BHMT), glycine N-methyltransferase (GNMT) and the DNA methyltransferase DNMT1. Moreover, mtDNA sequences coding for 12S, 16S rRNA and ND4, as well as the D-loop region were significantly hypermethylated in PCO oocytes. These results indicate that an abnormal activation of one-carbon metabolism and hypermethylation of mtDNA may contribute, largely, to the mitochondrial malfunction and decreased quality of PCO-derived oocytes in gilts.

  9. Mini-midi-mito: adapting the amplification and sequencing strategy of mtDNA to the degradation state of crime scene samples.

    PubMed

    Berger, Cordula; Parson, Walther

    2009-06-01

    The degradation state of some biological traces recovered from the crime scene requires the amplification of very short fragments to attain a useful mitochondrial (mt)DNA sequence. We have previously introduced two mini-multiplex assays that amplify 10 overlapping control region (CR) fragments in two separate multiplex PCRs, which brought successful CR consensus sequences from even highly degraded DNA extracts. This procedure requires a total of 20 sequencing reactions per sample, which is laborious and cost intensive. For only moderately degraded samples that we encounter more frequently with typical mtDNA casework material, we developed two new multiplex assays that use a subset of the mini-amplicon primers but embrace larger fragments (midis) and require only 10 sequencing reactions to build a double-stranded CR consensus sequence. We used a preceding mtDNA quantitation step by real-time PCR with two different target fragments (143 and 283 bp) that roughly correspond to the average fragment sizes of the different multiplex approaches to estimate size-dependent mtDNA quantities and to aid the choice of the appropriate PCR multiplexes with respect to quality of the results and required costs.

  10. Microchip capillary electrophoresis protocol to evaluate quality and quantity of mtDNA amplified fragments for DNA sequencing in forensic genetics.

    PubMed

    Fernández, Coro; Alonso, Antonio

    2012-01-01

    Here, we describe a microcapillary electrophoresis technique with application to the quantitative analysis of mtDNA hypervariable regions HVR1, HVR2, and HVR3 PCR amplicons previous to sequence analysis, which yields several important advantages compared to traditional separation and detection methods. Based on laser-induced fluorescence (LIF) detection, and performed in a microchip, this analysis system enables the handling of very small volumes via microchannels etched in the chip. Moreover it is faster than traditional methods; chip priming and sample loading are the only manual interventions, as the rest of the process is fully automated by software control: injection, electrophoretic separation, detection of the fluorescent signal, and calculation of both quantity and size. MtDNA amplicons are separated in microchannels with an effective length of 15 mm and detected by means of the fluorescence displayed by an intercalated dye. A software records the fluorescence and entails the data into size and concentration through the use of two internal standards and an external ladder of 11 fragments. The effectiveness of this procedure has been illustrated with a validation experiment carried out in our laboratory, in order to assess the detection limit of mtDNA sequencing by determining the minimal amount of PCR amplicon needed to edit a reproducible and high quality mtDNA sequence from complementary sequence data obtained using forward and reverse primers.

  11. Identification of interacting partners of Human Mpv17-like protein with a mitigating effect of mitochondrial dysfunction through mtDNA damage.

    PubMed

    Iida, Reiko; Ueki, Misuzu; Yasuda, Toshihiro

    2015-10-01

    Human Mpv17-like protein (M-LPH) has been suggested to participate in mitochondrial function. In this study, we investigated the proteins that interact with M-LPH, and identified four: H2A histone family, member X (H2AX), ribosomal protein S14 (RPS14), ribosomal protein S3 (RPS3) and B-cell receptor-associated protein 31 (Bap31). Immunofluorescence and subcellular fractionation studies revealed that M-LPH is localized predominantly in the nucleus, to some extent in a subset of mitochondria, and marginally in the cytosol. Mitochondrial M-LPH appeared as punctate foci, and these were co-localized with a subset of mitochondrial transcription factor A (TFAM) and mtDNA, indicating that M-LPH is localized in or in close proximity to mitochondrial nucleoids. RNAi-mediated knockdown of M-LPH resulted in an increase of mtDNA damage and reduced the expression of mtDNA-encoded genes. A ROS inducer, antimycin A, caused an increase in both the number and size of the mitochondrial M-LPH foci, and these foci were co-localized with two enzymes, DNA polymerase γ (POLG) and DNA ligase III (LIG3), both involved in mtDNA repair. Furthermore, knockdown of M-LPH hampered mitochondrial localization of these enzymes. Taken together, these observations suggest that M-LPH is involved in the maintenance of mtDNA and protects cells from mitochondrial dysfunction.

  12. Association of mitochondrial antioxidant enzymes with mitochondrial DNA as integral nucleoid constituents

    PubMed Central

    Kienhöfer, Joachim; Häussler, Dagmar Johanna Franziska; Ruckelshausen, Florian; Muessig, Elisabeth; Weber, Klaus; Pimentel, David; Ullrich, Volker; Bürkle, Alexander; Bachschmid, Markus Michael

    2009-01-01

    Mitochondrial DNA (mtDNA) is organized in protein-DNA macrocomplexes called nucleoids. Average nucleoids contain 2–8 mtDNA molecules, which are organized by the histone-like mitochondrial transcription factor A. Besides well-characterized constituents, such as single-stranded binding protein or polymerase γ (Polγ), various other proteins with ill-defined functions have been identified. We report for the first time that mammalian nucleoids contain essential enzymes of an integral antioxidant system. Intact nucleoids were isolated with sucrose density gradients from rat and bovine heart as well as human Jurkat cells. Manganese superoxide dismutase (SOD2) was detected by Western blot in the nucleoid fractions. DNA, mitochondrial glutathione peroxidase (GPx1), and Polγ were coimmunoprecipitated with SOD2 from nucleoid fractions, which suggests that an antioxidant system composed of SOD2 and GPx1 are integral constituents of nucleoids. Interestingly, in cultured bovine endothelial cells the association of SOD2 with mtDNA was absent. Using a sandwich filter-binding assay, direct association of SOD2 by salt-sensitive ionic forces with a chemically synthesized mtDNA fragment was demonstrated. Increasing salt concentrations during nucleoid isolation on sucrose density gradients disrupted the association of SOD2 with mitochondrial nucleoids. Our biochemical data reveal that nucleoids contain an integral antioxidant system that may protect mtDNA from superoxide-induced oxidative damage.—Kienhöfer, J., Häussler, D. J. F., Ruckelshausen, F., Muessig, E., Weber, K., Pimentel, D., Ullrich, V., Bürkle, A., Bachschmid, M. M. Association of mitochondrial antioxidant enzymes with mitochondrial DNA as integral nucleoid constituents. PMID:19228881

  13. Previous estimates of mitochondrial DNA mutation level variance did not account for sampling error: comparing the mtDNA genetic bottleneck in mice and humans.

    PubMed

    Wonnapinij, Passorn; Chinnery, Patrick F; Samuels, David C

    2010-04-09

    In cases of inherited pathogenic mitochondrial DNA (mtDNA) mutations, a mother and her offspring generally have large and seemingly random differences in the amount of mutated mtDNA that they carry. Comparisons of measured mtDNA mutation level variance values have become an important issue in determining the mechanisms that cause these large random shifts in mutation level. These variance measurements have been made with samples of quite modest size, which should be a source of concern because higher-order statistics, such as variance, are poorly estimated from small sample sizes. We have developed an analysis of the standard error of variance from a sample of size n, and we have defined error bars for variance measurements based on this standard error. We calculate variance error bars for several published sets of measurements of mtDNA mutation level variance and show how the addition of the error bars alters the interpretation of these experimental results. We compare variance measurements from human clinical data and from mouse models and show that the mutation level variance is clearly higher in the human data than it is in the mouse models at both the primary oocyte and offspring stages of inheritance. We discuss how the standard error of variance can be used in the design of experiments measuring mtDNA mutation level variance. Our results show that variance measurements based on fewer than 20 measurements are generally unreliable and ideally more than 50 measurements are required to reliably compare variances with less than a 2-fold difference.

  14. A trans-Amazonian screening of mtDNA reveals deep intraspecific divergence in forest birds and suggests a vast underestimation of species diversity.

    PubMed

    Milá, Borja; Tavares, Erika S; Muñoz Saldaña, Alberto; Karubian, Jordan; Smith, Thomas B; Baker, Allan J

    2012-01-01

    The Amazonian avifauna remains severely understudied relative to that of the temperate zone, and its species richness is thought to be underestimated by current taxonomy. Recent molecular systematic studies using mtDNA sequence reveal that traditionally accepted species-level taxa often conceal genetically divergent subspecific lineages found to represent new species upon close taxonomic scrutiny, suggesting that intraspecific mtDNA variation could be useful in species discovery. Surveys of mtDNA variation in Holarctic species have revealed patterns of variation that are largely congruent with species boundaries. However, little information exists on intraspecific divergence in most Amazonian species. Here we screen intraspecific mtDNA genetic variation in 41 Amazonian forest understory species belonging to 36 genera and 17 families in 6 orders, using 758 individual samples from Ecuador and French Guiana. For 13 of these species, we also analyzed trans-Andean populations from the Ecuadorian Chocó. A consistent pattern of deep intraspecific divergence among trans-Amazonian haplogroups was found for 33 of the 41 taxa, and genetic differentiation and genetic diversity among them was highly variable, suggesting a complex range of evolutionary histories. Mean sequence divergence within families was the same as that found in North American birds (13%), yet mean intraspecific divergence in Neotropical species was an order of magnitude larger (2.13% vs. 0.23%), with mean distance between intraspecific lineages reaching 3.56%. We found no clear relationship between genetic distances and differentiation in plumage color. Our results identify numerous genetically and phenotypically divergent lineages which may result in new species-level designations upon closer taxonomic scrutiny and thorough sampling, although lineages in the tropical region could be older than those in the temperate zone without necessarily representing separate species. In-depth phylogeographic surveys

  15. Comprehensive study of mtDNA among Southwest Asian dogs contradicts independent domestication of wolf, but implies dog–wolf hybridization

    PubMed Central

    Ardalan, Arman; Kluetsch, Cornelya F C; Zhang, Ai-bing; Erdogan, Metin; Uhlén, Mathias; Houshmand, Massoud; Tepeli, Cafer; Ashtiani, Seyed Reza Miraei; Savolainen, Peter

    2011-01-01

    Studies of mitochondrial DNA (mtDNA) diversity indicate explicitly that dogs were domesticated, probably exclusively, in southern East Asia. However, Southwest Asia (SwAsia) has had poor representation and geographical coverage in these studies. Other studies based on archaeological and genome-wide SNP data have suggested an origin of dogs in SwAsia. Hence, it has been suspected that mtDNA evidence for this scenario may have remained undetected. In the first comprehensive investigation of genetic diversity among SwAsian dogs, we analyzed 582 bp of mtDNA for 345 indigenous dogs from across SwAsia, and compared with 1556 dogs across the Old World. We show that 97.4% of SwAsian dogs carry haplotypes belonging to a universal mtDNA gene pool, but that only a subset of this pool, five of the 10 principal haplogroups, is represented in SwAsia. A high frequency of haplogroup B, potentially signifying a local origin, was not paralleled with the high genetic diversity expected for a center of origin. Meanwhile, 2.6% of the SwAsian dogs carried the rare non-universal haplogroup d2. Thus, mtDNA data give no indication that dogs originated in SwAsia through independent domestication of wolf, but dog–wolf hybridization may have formed the local haplogroup d2 within this region. Southern East Asia remains the only region with virtually full extent of genetic variation, strongly indicating it to be the primary and probably sole center of wolf domestication. An origin of dogs in southern East Asia may have been overlooked by other studies due to a substantial lack of samples from this region. PMID:22393507

  16. The Amerindian mtDNA haplogroup B2 enhances the risk of HPV for cervical cancer: de-regulation of mitochondrial genes may be involved.

    PubMed

    Guardado-Estrada, Mariano; Medina-Martínez, Ingrid; Juárez-Torres, Eligia; Roman-Bassaure, Edgar; Macías, Luis; Alfaro, Ana; Alcántara-Vázquez, Avissai; Alonso, Patricia; Gomez, Guillermo; Cruz-Talonia, Fernando; Serna, Luis; Muñoz-Cortez, Sergio; Borges-Ibañez, Manuel; Espinosa, Ana; Kofman, Susana; Berumen, Jaime

    2012-04-01

    Although human papillomavirus (HPV) infection is the main causal factor for cervical cancer (CC), there are data suggesting that genetic factors could modulate the risk for CC. Sibling studies suggest that maternally inherited factors could be involved in CC. To assess whether mitochondrial DNA (mtDNA) polymorphisms are associated to CC, HPV infection and HPV types, a case-control study was performed in the Mexican population. Polymorphism of mtDNA D-loop was investigated in 187 CC patients and 270 healthy controls. HPV was detected and typed in cervical scrapes. The expression of 29 mitochondrial genes was analyzed in a subset of 45 tumor biopsies using the expression microarray ST1.0. The Amerindian haplogroup B2 increased the risk for CC (odds ratio (OR)=1.6; 95% confidence interval (CI): 1.05-2.58) and enhanced 36% (OR=208; 95% CI: 25.2-1735.5) the risk conferred by the HPV alone (OR=152.9; 95% CI: 65.4-357.5). In cases, the distribution of HPV types was similar in all haplogroups but one (D1), in which is remarkable the absence of HPV18, a very low frequency of HPV16 and high frequencies of HPV45, HPV31 and other HPV types. Two mtDNA genes (mitochondrial aspartic acid tRNA (MT-TD), mitochondrial lysine tRNA (MT-TK)) could be involved in the increased risk conferred by the haplogroup B2, as they were upregulated exclusively in B2 tumors (P<0.01, t-test). Although the association of mtDNA with CC and HPV infection is clear, other studies with higher sample size will be needed to elucidate the role of mtDNA in cervical carcinogenesis.

  17. Determination of population origin: a comparison of autosomal SNPs, Y-chromosomal and mtDNA haplogroups using a Malagasy population as example.

    PubMed

    Poetsch, Micaela; Wiegand, Aline; Harder, Melanie; Blöhm, Rowena; Rakotomavo, Noel; Freitag-Wolf, Sandra; von Wurmb-Schwark, Nicole

    2013-12-01

    Y-chromosomal and mitochondrial DNA (mtDNA) polymorphisms have been used for population studies for a long time. However, there is another possibility to define the origin of a population: autosomal single-nucleotide polymorphisms (SNPs) whose allele frequencies differ considerably in different populations. In an attempt to compare the usefulness of these approaches we studied a population from Madagascar using all the three mentioned approaches. Former investigations of Malagasy maternal (mtDNA) and paternal (Y chromosome) lineages have led to the assumption that the Malagasy are an admixed population with an African and Asian-Indonesian heritage. Our additional study demonstrated that more than two-third of the Malagasy investigated showed clearly a West African genotype regarding only the autosomal SNPs despite the fact that 64% had an Asian mtDNA and more than 70% demonstrated an Asian-Indonesian heritage in either mtDNA or Y-chromosomal haplogroup or both. Nonetheless, the admixture of the Malagasy could be confirmed. A clear African or Asian-Indonesian heritage according to all the three DNA approaches investigated was only found in 14% and 1% of male samples, respectively. Not even the European or Northern African influences, detected in 9% of males (Y-chromosomal analysis) and 11% of samples (autosomal SNPs) were consistent. No Malagasy in our samples showed a European or Northern African origin in both categories. So, the analysis of autosomal SNPs could confirm the admixed character of the Malagasy population, even if it pointed to a greater African influence as detectable by Y-chromosomal or mtDNA analysis.

  18. COII/tRNA[sup Lys] intergenic 9-bp deletion and other mtDNA markers clearly reveal that the Tharus (Southern Nepal) have oriental affinities

    SciTech Connect

    Passarino, G.; Semino, O.; Santachiara-Benerecetti, A.S.; Modiano, G. )

    1993-09-01

    The authors searched for the East Asian mtDNA 9-bp deletion in the intergenic COII/tRNA[sup Lys] region in a sample of 107 Tharus (50 from central Terai and 57 from eastern Terai), a population whose anthropological origin has yet to be completely clarified. The deletion, detected by electrophoresis of the PCR-amplified nt 7392-8628 mtDNA fragment after digestion with HaeIII, was found in about 8% of both Tharu groups but was found in none of the 76 Hindus who were examined as a non-Oriental neighboring control population. A complete triplication of the 9-bp unit, the second case so far reported, was also observed in one eastern Tharu. All the mtDNAs with the deletion, and that with the triplication, were further characterized (by PCR amplification of the relevant mTDNA fragments and their digestion with the appropriate enzymes) to locate them in the Ballinger et al. phylogeny of East Asian mtDNA haplotypes. The deletion was found to be associated with four different haplotypes, two of which are reported for the first time. One of the deletions and especially the triplication could be best explained by the assumption of novel length-change events. Ballinger's classification of East Asian mtDNA haplotypes is mainly based on the phenotypes for the DdeI site at nt 10394 and the AluI site at nt 10397. Analysis of the entire Tharu sample revealed that more than 70% of the Tharus have both sites, the association of which has been suggested as an ancient East Asian peculiarity. These results conclusively indicate that the Tharus have a predominantly maternal Oriental ancestry. Moreover, they show at least one and perhaps two further distinct length mutations, and this suggests that the examined region is a hot spot of rearrangements. 21 refs., 5 figs., 6 tabs.

  19. Unexpected population genetic structure of European roe deer in Poland: an invasion of the mtDNA genome from Siberian roe deer.

    PubMed

    Matosiuk, Maciej; Borkowska, Anetta; Świsłocka, Magdalena; Mirski, Paweł; Borowski, Zbigniew; Krysiuk, Kamil; Danilkin, Aleksey A; Zvychaynaya, Elena Y; Saveljev, Alexander P; Ratkiewicz, Mirosław

    2014-05-01

    Introgressive hybridization is a widespread evolutionary phenomenon which may lead to increased allelic variation at selective neutral loci and to transfer of fitness-related traits to introgressed lineages. We inferred the population genetic structure of the European roe deer (Capreolus capreolus) in Poland from mitochondrial (CR and cyt b) and sex-linked markers (ZFX, SRY, DBY4 and DBY8). Analyses of CR mtDNA sequences from 452 individuals indicated widespread introgression of Siberian roe deer (C. pygargus) mtDNA in the European roe deer genome, 2000 km from the current distribution range of C. pygargus. Introgressed individuals constituted 16.6% of the deer studied. Nearly 75% of them possessed haplotypes belonging to the group which arose 23 kyr ago and have not been detected within the natural range of Siberian roe deer, indicating that majority of present introgression has ancient origin. Unlike the mtDNA results, sex-specific markers did not show signs of introgression. Species distribution modelling analyses suggested that C. pygargus could have extended its range as far west as Central Europe after last glacial maximum. The main hybridization event was probably associated with range expansion of the most abundant European roe deer lineage from western refugia and took place in Central Europe after the Younger Dryas (10.8-10.0 ka BP). Initially, introgressed mtDNA variants could have spread out on the wave of expansion through the mechanism of gene surfing, reaching high frequencies in European roe deer populations and leading to observed asymmetrical gene flow. Human-mediated introductions of C. pygargus had minimal effect on the extent of mtDNA introgression.

  20. A Trans-Amazonian Screening of mtDNA Reveals Deep Intraspecific Divergence in Forest Birds and Suggests a Vast Underestimation of Species Diversity

    PubMed Central

    Milá, Borja; Tavares, Erika S.; Muñoz Saldaña, Alberto; Karubian, Jordan; Smith, Thomas B.; Baker, Allan J.

    2012-01-01

    The Amazonian avifauna remains severely understudied relative to that of the temperate zone, and its species richness is thought to be underestimated by current taxonomy. Recent molecular systematic studies using mtDNA sequence reveal that traditionally accepted species-level taxa often conceal genetically divergent subspecific lineages found to represent new species upon close taxonomic scrutiny, suggesting that intraspecific mtDNA variation could be useful in species discovery. Surveys of mtDNA variation in Holarctic species have revealed patterns of variation that are largely congruent with species boundaries. However, little information exists on intraspecific divergence in most Amazonian species. Here we screen intraspecific mtDNA genetic variation in 41 Amazonian forest understory species belonging to 36 genera and 17 families in 6 orders, using 758 individual samples from Ecuador and French Guiana. For 13 of these species, we also analyzed trans-Andean populations from the Ecuadorian Chocó. A consistent pattern of deep intraspecific divergence among trans-Amazonian haplogroups was found for 33 of the 41 taxa, and genetic differentiation and genetic diversity among them was highly variable, suggesting a complex range of evolutionary histories. Mean sequence divergence within families was the same as that found in North American birds (13%), yet mean intraspecific divergence in Neotropical species was an order of magnitude larger (2.13% vs. 0.23%), with mean distance between intraspecific lineages reaching 3.56%. We found no clear relationship between genetic distances and differentiation in plumage color. Our results identify numerous genetically and phenotypically divergent lineages which may result in new species-level designations upon closer taxonomic scrutiny and thorough sampling, although lineages in the tropical region could be older than those in the temperate zone without necessarily representing separate species. In-depth phylogeographic surveys

  1. Segregation and manifestations of the mtDNA tRNA[sup Lys] A[r arrow]G[sup (8344)] mutation of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome

    SciTech Connect

    Larsson, N.G.; Tulinius, M.H.; Holme, E.; Oldfors, A.; Andersen, O.; Wahlstroem, J. ); Aasly, J. )

    1992-12-01

    The authors have studied the segregation and manifestations of the tRNA[sup Lys] A[r arrow]G[sup (8344)] mutation of mtDNA. Three unrelated patients with myoclonus epilepsy and ragged-red fibers (MERRF) syndrome were investigated, along with 30 of their maternal relatives. Mutated mtDNA was not always found in the offspring of women carrying the tRNA[sup Lys] mutation. Four women had 10%-33% of mutated mtDNA in lymphocytes, and no mutated mtDNA was found in 7 of their 14 investigated children. The presence of mutated mtDNA was excluded at a level of 3:1,000. Five women had a proportion of 43%-73% mutated mtDNA in lymphocytes, and mutated mtDNA was found in all their 12 investigated children. This suggests that the risk for transmission of mutated mtDNA to the offspring increases if high levels are present in the mother and that, above a threshold level of 35%-40%, it is very likely that transmission will occur to all children. The three patients with MERRF syndrone had, in muscle, both 94%-96% mutated mtDNA and biochemical and histochemical evidence of a respiratory-chain dysfunction. Four relatives had a proportion of 61%-92% mutated mtDNA in muscle, and biochemical measurements showed a normal respiratory-chain function in muscle in all cases. These findings suggest that >92% of mtDNA with the tRNA[sup Lys] mutation in muscle is required to cause a respiratory-chain dysfunction that can be detected by biochemical methods. There was a positive correlation between the levels of mtDNA with the tRNA[sup Lys] mutation in lymphocytes and the levels in muscle, in all nine investigated cases. The levels of mutated mtDNA were higher in muscle than in lymphocytes in all cases. 30 refs., 3 figs., 5 tabs.

  2. Adding resolution to ordinal level relationships of tapeworms (Platyhelminthes: Cestoda) with large fragments of mtDNA.

    PubMed

    Waeschenbach, Andrea; Webster, B L; Littlewood, D T J

    2012-06-01

    The construction of a stable phylogeny for the Cestoda, indicating the interrelationships of recognised orders and other major lineages, has proceeded iteratively since the group first received attention from phylogenetic systematists. Molecular analyses using nuclear ribosomal RNA gene fragments from the small (ssrDNA) and large (lsrDNA) subunits have been used to test competing evolutionary scenarios based on morphological data but could not arbitrate between some key conflicting hypotheses. To the ribosomal data, we have added a contiguous fragment of mitochondrial (mt) genome data (mtDNA) of partial nad1-trnN-trnP-trnI-trnK-nad3-trnS-trnW-cox1-trnT-rrnL-trnC-partial rrnS, spanning 4034-4447 bp, where new data for this region were generated for 18 species. Bayesian analysis of mtDNA and rDNA as nucleotides, and where appropriate as amino acids, demonstrated that these two classes of genes provide complementary signal across the phylogeny. In all analyses, except when using mt amino acids only, the Gyrocotylidea is sister group to all other Cestoda (Nephroposticophora), and Amphilinidea forms the sister group to the Eucestoda. However, an earliest-diverging position of Amphilinidea is strongly supported in the mt amino acid analysis. Amphilinidea exhibit a unique tRNA arrangement (nad1-trnI-trnL2-trnP-trnK-trnV-trnA-trnN-nad3), whereas Gyrocotylidea shares that of the derived lineages, providing additional evidence of the uniqueness of amphilinid genes and genomes. The addition of mtDNA to the rDNA genes supported the Caryophyllidea as the sister group to (Spathebothriidea+remaining Eucestoda), a hypothesis consistently supported by morphology. This relationship suggests a history of step-wise evolutionary transitions from simple monozoic, unsegmented tapeworms to the more familiar polyzoic, externally segmented (strobilate) forms. All our data partitions recovered Haplobothriidea as the sister group to Diphyllobothriidae. The sister-group relationship between

  3. Evidence of Subclinical mtDNA Alterations in HIV-Infected Pregnant Women Receiving Combination Antiretroviral Therapy Compared to HIV-Negative Pregnant Women

    PubMed Central

    Money, Deborah M.; Wagner, Emily C.; Maan, Evelyn J.; Chaworth-Musters, Tessa; Gadawski, Izabelle; van Schalkwyk, Julie E.; Forbes, John C.; Burdge, David R.; Albert, Arianne Y. K.; Lohn, Zoe; Côté, Hélène C. F.

    2015-01-01

    Introduction Combination antiretroviral therapy (cART) can effectively prevent vertical transmission of HIV but there is potential risk of adverse maternal, foetal or infant effects. Specifically, the effect of cART use during pregnancy on mitochondrial DNA (mtDNA) content in HIV-positive (HIV+) women is unclear. We sought to characterize subclinical alterations in peripheral blood mtDNA levels in cART-treated HIV+ women during pregnancy and the postpartum period. Methods This prospective longitudinal observational cohort study enrolled both HIV+ and HIV-negative (HIV-) pregnant women. Clinical data and blood samples were collected at three time points in pregnancy (13-<23 weeks, 23-<30 weeks, 30–40 weeks), and at delivery and six weeks post-partum in HIV+ women. Peripheral blood mtDNA to nuclear DNA (nDNA) ratio was measured by qPCR. Results Over a four year period, 63 HIV+ and 42 HIV- women were enrolled. HIV+ women showed significantly lower mtDNA/nDNA ratios compared to HIV- women during pregnancy (p = 0.003), after controlling for platelet count and repeated measurements using a multivariable mixed-effects model. Ethnicity, gestational age (GA) and substance use were also significantly associated with mtDNA/nDNA ratio (p≤0.02). Among HIV+ women, higher CD4 nadir was associated with higher mtDNA/nDNA ratios (p<0.0001), and these ratio were significantly lower during pregnancy compared to the postpartum period (p<0.0001). Conclusions In the context of this study, it was not possible to distinguish between mtDNA effects related to HIV infection versus cART therapy. Nevertheless, while mtDNA levels were relatively stable over time in both groups during pregnancy, they were significantly lower in HIV+ women compared to HIV- women. Although no immediate clinical impact was observed on maternal or infant health, lower maternal mtDNA levels may exert long-term effects on women and children and remain a concern. Improved knowledge of such subclinical alterations is

  4. Genetic diversity and population structure in Bactrocera correcta (Diptera: Tephritidae) inferred from mtDNA cox1 and microsatellite markers

    PubMed Central

    Qin, Yu-Jia; Buahom, Nopparat; Krosch, Matthew N.; Du, Yu; Wu, Yi; Malacrida, Anna R.; Deng, Yu-Liang; Liu, Jia-Qi; Jiang, Xiao-Long; Li, Zhi-Hong

    2016-01-01

    Bactrocera correcta is one of the most destructive pests of horticultural crops in tropical and subtropical regions. Despite the economic risk, the population genetics of this pest have remained relatively unexplored. This study explores population genetic structure and contemporary gene flow in B. correcta in Chinese Yunnan Province and attempts to place observed patterns within the broader geographical context of the species’ total range. Based on combined data from mtDNA cox1 sequences and 12 microsatellite loci obtained from 793 individuals located in 7 countries, overall genetic structuring was low. The expansion history of this species, including likely human-mediated dispersal, may have played a role in shaping the observed weak structure. The study suggested a close relationship between Yunnan Province and adjacent countries, with evidence for Western and/or Southern Yunnan as the invasive origin of B. correcta within Yunnan Province. The information gleaned from this analysis of gene flow and population structure has broad implications for quarantine, trade and management of this pest, especially in China where it is expanding northward. Future studies should concentrate effort on sampling South Asian populations, which would enable better inferences of the ancestral location of B. correcta and its invasion history into and throughout Asia. PMID:27929126

  5. Analysis of medieval mtDNA from Napole cemetery provides new insights into the early history of Polish state.

    PubMed

    Płoszaj, Tomasz; Jędrychowska-Dańska, Krystyna; Masłowska, Alicja; Kozłowski, Tomasz; Chudziak, Wojciech; Bojarski, Jacek; Robaszkiewicz, Agnieszka; Witas, Henryk W

    2017-02-01

    Contemporary historical anthropology and classical archaeology are concerned not only with such fundamental issues as the origins of ancient human populations and migration routes, but also with the formation and development of inter-population relations and the mixing of gene pools as a result of inter-breeding between individuals representing different cultural units. The contribution of immigrants to the analysed autochthonous population and their effect on the gene pool of that population has proven difficult to evaluate with classical morphological methods. The burial of one individual in the studied Napole cemetery located in central Poland had the form of a chamber grave, which is typical of Scandinavian culture from that period. However, this fact cannot be interpreted as absolute proof that the individual (in the biological sense) was allochtonous. This gives rise to the question as to who was actually buried in that cemetery. The ancient DNA results indicate that one of the individuals had an mtDNA haplotype typical of Iron Age northern Europe, which suggests that he could have arrived from that area at a later period. This seems to indirectly confirm the claims of many anthropologists that the development of the early medieval Polish state was significantly and directly influenced by the Scandinavians.

  6. Phylogeographic structure of Brachymystax lenok tsinlingensis (Salmonidae) populations in the Qinling Mountains, Shaanxi, based on mtDNA control region.

    PubMed

    Liu, Haixia; Li, Yang; Liu, Xiaolin; Xiong, Dongmei; Wang, Lixin; Zou, Guiwei; Wei, Qiwei

    2015-08-01

    Brachymystax lenok tsinlingensis is an endangered freshwater fish and distributed in mountains steams of Qinling Mountains, China. In this study, a comparative study of the mtDNA control region (D-loop) was performed to analyze its natural population structure and the genetic diversity of 53 individuals from four locations (TB, YX, LX and ZZ populations). Sequence analysis revealed three different domains and two feature sequences of the control region. The estimated haplotype and nucleotide diversity were 9 and 0.0023, respectively. Genetic structure analysis showed a high-level genetic diversity of B. lenok tisnlingensis (h = 0.6060 ± 0.1499). The AMOVA analysis indicated that 26.02% of total variation came from individual populations, and 73.98% from variation within the four geographic populations, which showed low genetic differentiation between the four geographic groups. Test of neutral evolution and mismatch distribution indicated that no historical expansion occurred in these populations. The high genetic diversity and low genetic differentiation would provide new information for conservation and exploitation of this species.

  7. mtDNA history of the Cayapa Amerinds of Ecuador: detection of additional founding lineages for the Native American populations.

    PubMed Central

    Rickards, O; Martínez-Labarga, C; Lum, J K; De Stefano, G F; Cann, R L

    1999-01-01

    mtDNA variation in the Cayapa, an Ecuadorian Amerindian tribe belonging to the Chibcha-Paezan linguistic branch, was analyzed by use of hypervariable control regions I and II along with two linked regions undergoing insertion/deletion mutations. Three major maternal lineage clusters fit into the A, B, and C founding groups first described by Schurr and colleagues in 1990, whereas a fourth lineage, apparently unique to the Cayapa, has ambiguous affinity to known clusters. The time of divergence from a common maternal ancestor of the four lineage groups is of sufficient age that it indicates an origin in Asia and supports the hypothesis that the degree of variability carried by the Asian ancestral populations into the New World was rather high. Spatial autocorrelation analysis points out (a) statistically significant nonrandom distributions of the founding lineages in the Americas, because of north-south population movements that have occurred since the first Asian migrants spread through Beringia into the Americas, and (b) an unusual pattern associated with the D lineage cluster. The values of haplotype and nucleotide diversity that are displayed by the Cayapa appear to differ from those observed in other Chibchan populations but match those calculated for South American groups belonging to various linguistic stocks. These data, together with the results of phylogenetic analysis performed with the Amerinds of Central and South America, highlight the difficulty in the identification of clear coevolutionary patterns between linguistic and genetic relationships in particular human populations. PMID:10417294

  8. mtDNA variation indicates Mongolia may have been the source for the founding population for the New World.

    PubMed Central

    Merriwether, D. A.; Hall, W. W.; Vahlne, A.; Ferrell, R. E.

    1996-01-01

    mtDNA RFLP variation was analyzed in 42 Mongolians from Ulan Bator. All four founding lineage types (A [4.76%], B [2.38%], C [11.9%], and D [19.04%]) identified by Torroni and colleagues were detected. Seven of the nine founding lineage types proposed by Bailliet and colleagues and Merriwether and Ferrell were detected (A2 [4.76%], B [2.38%], C1 [11.9%], D1 [7.14%], D2 [11.9%], X6 [16.7%], and X7 [9.5%]). Sixty-four percent of these 42 individuals had "Amerindian founding lineage" haplotypes. A survey of 24 restriction sites yielded 16 polymorphic sites and 21 different haplotypes. The presence of all four of the founding lineages identified by the Torroni group (and seven of Merriwether and Ferrell's nine founding lineages), combined with Mongolia's location with respect to the Bering Strait, indicates that Mongolia is a potential location for the origin of the founders of the New World. Since lineage B, which is widely distributed in the New World, is absent in Siberia, we conclude that Mongolia or a geographic location common to both contemporary Mongolians and American aboriginals is the more likely origin of the founders of the New World. PMID:8659526

  9. A new mtDNA COI gene lineage near An. janconnae of the Albitarsis Complex from Caribbean Colombia

    PubMed Central

    Gutiérrez, Lina A; Orrego, Lina M; Gómez, Giovan F; López, Andrés; Luckhart, Shirley; Conn, Jan E; Correa, Margarita M

    2011-01-01

    An understanding of the taxonomic status and vector distribution of anophelines is crucial to malaria control efforts. Previous phylogenetic analyses have supported the description of six species of the Neotropical malaria vector Anopheles (Nyssorhynchus) albitarsis s.l. (Diptera: Culicidae): Anopheles albitarsis, An. deaneorum, An. marajoara, An. oryzalimnetes, An. janconnae and An. albitarsis F. To evaluate the taxonomic status of An. albitarsis s.l. mosquitoes collected in various localities of the Colombian Caribbean region, specimens were analyzed using the complete mtDNA Cytochrome Oxidase I (COI) gene, the ribosomal DNA internal transcribed spacer 2 (ITS2) region and partial nuclear DNA White gene sequences. Phylogenetic analyses of the COI sequences detected a new lineage near An. janconnae in the Caribbean region of Colombia and determined its position relative to the other members of the complex. However, the ITS2 and White gene sequences lacked resolution to support a new lineage near An. janconnae or the An. janconnae clade. Nothing is known about the possible involvement in malaria transmission in Colombia of this new lineage, but its phylogenetic closeness to Anopheles janconnae, which has been incriminated in local malaria transmission in Brazil, is provocative. PMID:21225199

  10. Comparison between Mt-DNA D-Loop and Cyt B primers for porcine DNA detection in meat products

    NASA Astrophysics Data System (ADS)

    Hamzah, Azhana; Mutalib, Sahilah Abd.; Babji, Abdul Salam

    2013-11-01

    This study was conducted to detect the presence of porcine DNA in meat products in the market using conventional polymerase chain reaction (PCR) and commercial PCR-southern hybridization analysis. Porcine DNA detection in meat products was tested due to some issues associated with the adulteration of food products in Malaysia. This is an important issue especially for Halal authentication which is required for some religious practices such as in Islam and Hinduisms. Many techniques have been developed for determining the Halal status of food products. In this paper, mt-DNA D-loop primer and cytochrome (cyt) b were used to detect the presence of porcine DNA in meat products. Positive and negative controls were always present for each batch of extraction. DNA of raw pork meat was used as a positive control while nucleus free water is used as negative control. A pair of oligonucleotide primer was used namely Pork1 and Pork2 which produced amplicon of 531 base pair (bp) in size. While, PCR-southern hybridization was conducted using primers readily supplied by commercial PCR-Southern hybridization and produced amplicon with 276 bp in size. In the present study, demonstrated that none of the samples were contaminated with porcine residuals but selected samples with pork meat were positive. The species-specific PCR amplification yielded excellent results for identification of pork derivatives in food products and it is a potentially reliable and suitable technique in routine food analysis for Halal certification.

  11. Oxygen consumption rates and oxygen concentration in molt-4 cells and their mtDNA depleted (rho0) mutants.

    PubMed

    Shen, Jiangang; Khan, Nadeem; Lewis, Lionel D; Armand, Ray; Grinberg, Oleg; Demidenko, Eugene; Swartz, Harold

    2003-02-01

    Respiratory deficient cell lines are being increasingly used to elucidate the role of mitochondria and to understand the pathophysiology of mitochondrial genetic disease. We have investigated the oxygen consumption rates and oxygen concentration in wild-type (WT) and mitochondrial DNA (mtDNA) depleted (rho(0)) Molt-4 cells. Wild-type Molt-4 cells have moderate oxygen consumption rates, which were significantly reduced in the rho(0) cells. PCMB (p-chloromercurobenzoate) inhibited the oxygen consumption rates in both WT and rho(0) cells, whereas potassium cyanide decreased the oxygen consumption rates only in WT Molt-4 cells. Menadione sodium bisulfite (MSB) increased the oxygen consumption rates in both cell lines, whereas CCCP (carbonyl cyanide m-chlorophenylhydrazone) stimulated the oxygen consumption rates only in WT Molt-4 cells. Superoxide radical adducts were observed in both WT and rho(0) cells when stimulated with MSB. The formation of this adduct was inhibited by PCMB but not by potassium cyanide. These results suggest that the reactive oxygen species (ROS) induced by MSB were at least in part produced via a mitochondrial independent pathway. An oxygen gradient between the extra- and intracellular compartments was observed in WT Molt-4 cells, which further increased when cells were stimulated by CCCP and MSB. The results are consistent with our earlier findings suggesting that such oxygen gradients may be a general phenomenon found in most or all cell systems under appropriate conditions.

  12. Childhood mitochondrial encephalomyopathies: clinical course, diagnosis, neuroimaging findings, mtDNA mutations and outcome in six children

    PubMed Central

    2013-01-01

    Mitochondrial dysfunction manifests in many forms during childhood. There is no effective therapy for the condition; hence symptomatic therapy is the only option. The effect of symptomatic therapy are not well known. We present clinical course, diagnosis and effect of current treatments for six children suffering from mitochondrial encephalomyopathy identified by clinical demonstrations, brain MRI findings and DNA mutations. Two were male and four were female. Their age ranged between 2 and 17 years. Skeletal muscle biopsies were obtained in three and one showed misshaped and enlarged mitochondria under electron microscope. mtDNA mutation frequency was >30%. Five children were diagnosed with MELAS (mitochondrial encephalopathy, lactic acidosis, and strokelike episodes) and one with Leigh’s syndrome (LS). All were given cocktail and symptomatic treatments. One of the five MELAS children died from severe complications. The other four MELAS children remain alive; four showed improvement, and one remained unresponsive. Of the four who showed improvement, two do not have any abnormal signs and the other two have some degree of motor developmental delay and myotrophy. The LS child is doing well except for ataxia. Until better therapy such as mitochondrial gene therapy is available, cocktail and symptomatic treatments could at least stabilize these children. PMID:24069936

  13. Comparison of mtDNA haplogroups in Hungarians with four other European populations: a small incidence of descents with Asian origin.

    PubMed

    Nadasi, Edit; Gyurus, P; Czakó, Márta; Bene, Judit; Kosztolányi, Sz; Fazekas, Sz; Dömösi, P; Melegh, B

    2007-06-01

    Hungarians are unique among the other European populations because according to history, the ancient Magyars had come from the eastern side of the Ural Mountains and settled down in the Carpathian basin in the 9th century AD. Since variations in the human mitochondrial genome (mtDNA) are routinely used to infer the histories of different populations, we examined the distribution of restriction fragment length polymorphism (RFLP) sites of the mtDNA in apparently healthy, unrelated Hungarian subjects in order to collect data on the genetic origin of the Hungarian population. Among the 55 samples analyzed, the large majority belonged to haplogroups common in other European populations, however, three samples fulfilled the requirements of haplogroup M. Since haplogroup M is classified as a haplogroup characteristic mainly for Asian populations, the presence of haplogroup M found in approximately 5% of the total suggests that an Asian matrilineal ancestry, even if in a small incidence, can be detected among modern Hungarians.

  14. Sideroblastic anaemia and primary adrenal insufficiency due to a mitochondrial respiratory chain disorder in the absence of mtDNA deletion

    PubMed Central

    O'Grady, Michael J; Monavari, Ahmad A; Cotter, Melanie; Murphy, Nuala P

    2015-01-01

    A fatigued 8-year-old boy was found to have sideroblastic anaemia (haemoglobin 7.8 g/dL) which over time became transfusion dependent. Subtle neurological dysfunction, initially manifesting as mild spastic diplegia, was slowly progressive and ultimately led to wheelchair dependence. Elevated plasma lactate and urinary 3-methylglutaconate led to a muscle biopsy which confirmed partial complex IV deficiency. PCR in leucocytes and muscle was negative for mitochondrial DNA (mtDNA) deletions. Faltering growth prompted an insulin tolerance test which confirmed growth hormone sufficiency and adrenal insufficiency. Plasma renin was elevated and adrenal androgens were low, suggesting primary adrenal insufficiency. Glucocorticoid and mineralocorticoid replacement therapy was initiated. A renal tubular Fanconi syndrome and diabetes mellitus developed subsequently. Sideroblastic anaemia and primary adrenal insufficiency, both individually and collectively, are associated with mtDNA deletion; however, absence of the same does not exclude the possibility that sideroblastic anaemia and primary adrenal insufficiency are of mitochondrial origin. PMID:25721834

  15. Identification of a group of cryptic marine limpet species, Cellana karachiensis (Mollusca: Patellogastropoda) off Veraval coast, India, using mtDNA COI sequencing.

    PubMed

    Joseph, Sneha; Poriya, Paresh; Vakani, Bhavik; Singh, S P; Kundu, Rahul

    2016-01-01

    Present communication reports the phylogenetic relationship between three groups of a marine limpet having different color banding patterns using COI sequencing. Samples were sequenced for mtDNA COI gene using universal primer. Comparative BLAST revealed that all three types were around 99.59% identical with Cellana karachiensis, first record of this species from Indian coasts. Apart from the morphological variations, the mtDNA COI gene analysis revealed around 1% nucleotide variations between these three types. The observed dissimilarity in COI sequences was possibly too little to consider these types as three different species. The derivation of amino acid positions indicated that these types could possibly be a complex of three cryptic species of C. karachiensis. The study proposes that the Oman and Indian populations of C. karachiensis might have derived by allopatric speciation due to geographical isolation. The group of these three cryptic species, sharing same habitat between themselves, possibly showed sympatric speciation.

  16. Detection of the mtDNA 14484 mutation on an African-specific haplotype: Implications about its role in causing Leber hereditary optic neuropathy

    SciTech Connect

    Torroni, A.; Petrozzi, M.; Terracina, M.

    1996-07-01

    Leber hereditary optic neuropathy (LHON) is a maternally transmitted disease whose primary clinical manifestation is acute or subacute bilateral loss of central vision leading to central scotoma and blindness. To date, LHON has been associated with 18 mtDNA missense mutations, even though, for many of these mutations, it remains unclear whether they cause the disease, contribute to the pathology, or are nonpathogenic mtDNA polymorphisms. On the basis of numerous criteria, which include the specificity for LHON, the frequency in the general population, and the penetrance within affected pedigrees, the detection of associated defects in the respiratory chain, mutations at three nucleotide positions (nps), 11778 (G{r_arrow}A), 3460 (G{r_arrow}A), and 14484 (T{r_arrow}C) have been classified as high-risk and primary LHON mutations. Overall, these three mutations encompass {ge}90% of the LHON cases. 29 refs., 1 fig.

  17. Mesenchymal stem cells transfer mitochondria to the cells with virtually no mitochondrial function but not with pathogenic mtDNA mutations.

    PubMed

    Cho, Young Min; Kim, Ju Han; Kim, Mingoo; Park, Su Jin; Koh, Sang Hyeok; Ahn, Hyo Seop; Kang, Gyeong Hoon; Lee, Jung-Bin; Park, Kyong Soo; Lee, Hong Kyu

    2012-01-01

    It has been reported that human mesenchymal stem cells (MSCs) can transfer mitochondria to the cells with severely compromised mitochondrial function. We tested whether the reported intercellular mitochondrial transfer could be replicated in different types of cells or under different experimental conditions, and tried to elucidate possible mechanism. Using biochemical selection methods, we found exponentially growing cells in restrictive media (uridine(-) and bromodeoxyuridine [BrdU](+)) during the coculture of MSCs (uridine-independent and BrdU-sensitive) and 143B-derived cells with severe mitochondrial dysfunction induced by either long-term ethidium bromide treatment or short-term rhodamine 6G (R6G) treatment (uridine-dependent but BrdU-resistant). The exponentially growing cells had nuclear DNA fingerprint patterns identical to 143B, and a sequence of mitochondrial DNA (mtDNA) identical to the MSCs. Since R6G causes rapid and irreversible damage to mitochondria without the removal of mtDNA, the mitochondrial function appears to be restored through a direct transfer of mitochondria rather than mtDNA alone. Conditioned media, which were prepared by treating mtDNA-less 143B ρ(0) cells under uridine-free condition, induced increased chemotaxis in MSC, which was also supported by transcriptome analysis. Cytochalasin B, an inhibitor of chemotaxis and cytoskeletal assembly, blocked mitochondrial transfer phenomenon in the above condition. However, we could not find any evidence of mitochondrial transfer to the cells harboring human pathogenic mtDNA mutations (A3243G mutation or 4,977 bp deletion). Thus, the mitochondrial transfer is limited to the condition of a near total absence of mitochondrial function. Elucidation of the mechanism of mitochondrial transfer will help us create a potential cell therapy-based mitochondrial restoration or mitochondrial gene therapy for human diseases caused by mitochondrial dysfunction.

  18. Application of a west Eurasian-specific filter for quasi-median network analysis: Sharpening the blade for mtDNA error detection

    PubMed Central

    Zimmermann, Bettina; Röck, Alexander; Huber, Gabriela; Krämer, Tanja; Schneider, Peter M.; Parson, Walther

    2011-01-01

    The application of quasi-median networks provides an effective tool to check the quality of mtDNA data. Filtering of highly recurrent mutations prior to network analysis is required to simplify the data set and reduce the complexity of the network. The phylogenetic background determines those mutations that need to be filtered. While the traditional EMPOPspeedy filter was based on the worldwide mtDNA phylogeny, haplogroup-specific filters can more effectively highlight potential errors in data of the respective (sub)-continental region. In this study we demonstrate the performance of a new, west Eurasian filter EMPOPspeedyWE for the fine-tuned examination of data sets belonging to macrohaplogroup N that constitutes the main portion of mtDNA lineages in Europe. The effects on the resulting network of different database sizes, high-quality and flawed data, as well as the examination of a phylogenetically distant data set, are presented by examples. The analyses are based on a west Eurasian etalon data set that was carefully compiled from more than 3500 control region sequences for network purposes. Both, etalon data and the new filter file, are provided through the EMPOP database (www.empop.org). PMID:21067984

  19. Genetic differences between Chibcha and Non-Chibcha speaking tribes based on mitochondrial DNA (mtDNA) haplogroups from 21 Amerindian tribes from Colombia

    PubMed Central

    Usme-Romero, Solangy; Alonso, Milena; Hernandez-Cuervo, Helena; Yunis, Emilio J.; Yunis, Juan J.

    2013-01-01

    We analyzed the frequency of four mitochondrial DNA haplogroups in 424 individuals from 21 Colombian Amerindian tribes. Our results showed a high degree of mtDNA diversity and genetic heterogeneity. Frequencies of mtDNA haplogroups A and C were high in the majority of populations studied. The distribution of these four mtDNA haplogroups from Amerindian populations was different in the northern region of the country compared to those in the south. Haplogroup A was more frequently found among Amerindian tribes in northern Colombia, while haplogroup D was more frequent among tribes in the south. Haplogroups A, C and D have clinal tendencies in Colombia and South America in general. Populations belonging to the Chibcha linguistic family of Colombia and other countries nearby showed a strong genetic differentiation from the other populations tested, thus corroborating previous findings. Genetically, the Ingano, Paez and Guambiano populations are more closely related to other groups of south eastern Colombia, as also inferred from other genetic markers and from archeological data. Strong evidence for a correspondence between geographical and linguistic classification was found, and this is consistent with evidence that gene flow and the exchange of customs and knowledge and language elements between groups is facilitated by close proximity. PMID:23885195

  20. MtDNA COI-COII marker and drone congregation area: an efficient method to establish and monitor honeybee (Apis mellifera L.) conservation centres.

    PubMed

    Bertrand, Bénédicte; Alburaki, Mohamed; Legout, Hélène; Moulin, Sibyle; Mougel, Florence; Garnery, Lionel

    2015-05-01

    Honeybee subspecies have been affected by human activities in Europe over the past few decades. One such example is the importation of nonlocal subspecies of bees which has had an adverse impact on the geographical repartition and subsequently on the genetic diversity of the black honeybee Apis mellifera mellifera. To restore the original diversity of this local honeybee subspecies, different conservation centres were set up in Europe. In this study, we established a black honeybee conservation centre Conservatoire de l'Abeille Noire d'Ile de France (CANIF) in the region of Ile-de-France, France. CANIF's honeybee colonies were intensively studied over a 3-year period. This study included a drone congregation area (DCA) located in the conservation centre. MtDNA COI-COII marker was used to evaluate the genetic diversity of CANIF's honeybee populations and the drones found and collected from the DCA. The same marker (mtDNA) was used to estimate the interactions and the haplotype frequency between CANIF's honeybee populations and 10 surrounding honeybee apiaries located outside of the CANIF. Our results indicate that the colonies of the conservation centre and the drones of the DCA show similar stable profiles compared to the surrounding populations with lower level of introgression. The mtDNA marker used on both DCA and colonies of the conservation centre seems to be an efficient approach to monitor and maintain the genetic diversity of the protected honeybee populations.

  1. Drawing the history of the Hutterite population on a genetic landscape: inference from Y-chromosome and mtDNA genotypes

    PubMed Central

    Pichler, Irene; Fuchsberger, Christian; Platzer, Christa; Çalişkan, Minal; Marroni, Fabio; Pramstaller, Peter P; Ober, Carole

    2010-01-01

    Although the North American Hutterites trace their origins to South Tyrol, no attempts have been made to examine the genetic migration history of the Hutterites before emigrating to the United States in the 1870s. To investigate this, we studied 9 microsatellite loci and 11 unique event polymorphism (UEP) markers on the Y-chromosome, the hypervariable region I (HVRI) of the mitochondrial DNA (mtDNA), as well as the complete mtDNA genome of Hutterite and South Tyrolean samples. Only 6 out of 14 Y-chromosome UEP+microsatellite haplotypes and 3 out of 11 mitochondrial haplotypes that were present in the Hutterites were also present in the South Tyrolean population. The phylogenetic relationships inferred from Y-chromosome and mtDNA databases show that the Hutterites have a unique genetic background related to a similar extent to central and eastern European populations. An admixture analysis indicates, however, a relatively high genetic contribution of central European populations to the Hutterite gene pool. These results are consistent with historical records on Hutterite migrations and demographic history. In addition, our data reveal similar numbers of Y and mitochondrial haplotypes in Hutterite male and female founders, respectively. The Hutterite male and female gene pools are similar with respect to genetic diversity and genetic distance measures and comparable with respect to their origins, suggesting a similar evolutionary history. PMID:19844259

  2. AAV-mediated liver-specific MPV17 expression restores mtDNA levels and prevents diet-induced liver failure.

    PubMed

    Bottani, Emanuela; Giordano, Carla; Civiletto, Gabriele; Di Meo, Ivano; Auricchio, Alberto; Ciusani, Emilio; Marchet, Silvia; Lamperti, Costanza; d'Amati, Giulia; Viscomi, Carlo; Zeviani, Massimo

    2014-01-01

    Mutations in human MPV17 cause a hepatocerebral form of mitochondrial DNA depletion syndrome (MDS) hallmarked by early-onset liver failure, leading to premature death. Liver transplantation and frequent feeding using slow-release carbohydrates are the only available therapies, although surviving patients eventually develop slowly progressive peripheral and central neuropathy. The physiological role of Mpv17, including its functional link to mitochondrial DNA (mtDNA) maintenance, is still unclear. We show here that Mpv17 is part of a high molecular weight complex of unknown composition, which is essential for mtDNA maintenance in critical tissues, i.e. liver, of a Mpv17 knockout mouse model. On a standard diet, Mpv17-/- mouse shows hardly any symptom of liver dysfunction, but a ketogenic diet (KD) leads these animals to liver cirrhosis and failure. However, when expression of human MPV17 is carried out by adeno-associated virus (AAV)-mediated gene replacement, the Mpv17 knockout mice are able to reconstitute the Mpv17-containing supramolecular complex, restore liver mtDNA copy number and oxidative phosphorylation (OXPHOS) proficiency, and prevent liver failure induced by the KD. These results open new therapeutic perspectives for the treatment of MPV17-related liver-specific MDS.

  3. Stimulation of macroautophagy can rescue older cells from 8-OHdG mtDNA accumulation: a safe and easy way to meet goals in the SENS agenda.

    PubMed

    Donati, Alessio; Taddei, Michele; Cavallini, Gabriella; Bergamini, Ettore

    2006-01-01

    Reduction of oxidative stress within mitochondria is a major focus and important part in the SENS agenda. The age-related accumulation of mitochondria rich in oxidatively altered DNA may be a biomarker of malfunctioning and increased oxidative stress. Macroautophagy is the cell repair mechanism responsible for the disposal of excess or altered mitochondria under the inhibitory control of nutrition and insulin, and may mediate the antiaging effects of caloric restriction. The authors investigated the effects of stimulation of macroautophagy by the injection of an antilipolytic agent on the age-related accumulation of oxidatively altered mitochondrial DNA (mtDNA) in rat liver cells. Results showed that treatment rescued older cells from the accumulation of 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the mtDNA in less than 6 hours. It is concluded that the age-related changes in mtDNA and function are likely to be the consequence of a failure of macroautophagy in the recognition and disposal of a small number of severely injured mitochondria, and that easy and safe ways are available to counteract this change.

  4. Simultaneous detection of human mitochondrial DNA and nuclear-inserted mitochondrial-origin sequences (NumtS) using forensic mtDNA amplification strategies and pyrosequencing technology.

    PubMed

    Bintz, Brittania J; Dixon, Groves B; Wilson, Mark R

    2014-07-01

    Next-generation sequencing technologies enable the identification of minor mitochondrial DNA variants with higher sensitivity than Sanger methods, allowing for enhanced identification of minor variants. In this study, mixtures of human mtDNA control region amplicons were subjected to pyrosequencing to determine the detection threshold of the Roche GS Junior(®) instrument (Roche Applied Science, Indianapolis, IN). In addition to expected variants, a set of reproducible variants was consistently found in reads from one particular amplicon. A BLASTn search of the variant sequence revealed identity to a segment of a 611-bp nuclear insertion of the mitochondrial control region (NumtS) spanning the primer-binding sites of this amplicon (Nature 1995;378:489). Primers (Hum Genet 2012;131:757; Hum Biol 1996;68:847) flanking the insertion were used to confirm the presence or absence of the NumtS in buccal DNA extracts from twenty donors. These results further our understanding of human mtDNA variation and are expected to have a positive impact on the interpretation of mtDNA profiles using deep-sequencing methods in casework.

  5. Helena, the hidden beauty: Resolving the most common West Eurasian mtDNA control region haplotype by massively parallel sequencing an Italian population sample.

    PubMed

    Bodner, Martin; Iuvaro, Alessandra; Strobl, Christina; Nagl, Simone; Huber, Gabriela; Pelotti, Susi; Pettener, Davide; Luiselli, Donata; Parson, Walther

    2015-03-01

    The analysis of mitochondrial (mt)DNA is a powerful tool in forensic genetics when nuclear markers fail to give results or maternal relatedness is investigated. The mtDNA control region (CR) contains highly condensed variation and is therefore routinely typed. Some samples exhibit an identical haplotype in this restricted range. Thus, they convey only weak evidence in forensic queries and limited phylogenetic information. However, a CR match does not imply that also the mtDNA coding regions are identical or samples belong to the same phylogenetic lineage. This is especially the case for the most frequent West Eurasian CR haplotype 263G 315.1C 16519C, which is observed in various clades within haplogroup H and occurs at a frequency of 3-4% in many European populations. In this study, we investigated the power of massively parallel complete mtGenome sequencing in 29 Italian samples displaying the most common West Eurasian CR haplotype - and found an unexpected high diversity. Twenty-eight different haplotypes falling into 19 described sub-clades of haplogroup H were revealed in the samples with identical CR sequences. This study demonstrates the benefit of complete mtGenome sequencing for forensic applications to enforce maximum discrimination, more comprehensive heteroplasmy detection, as well as highest phylogenetic resolution.

  6. Cybrid studies establish the causal link between the mtDNA m.3890G>A/MT-ND1 mutation and optic atrophy with bilateral brainstem lesions

    PubMed Central

    Caporali, Leonardo; Ghelli, Anna Maria; Iommarini, Luisa; Maresca, Alessandra; Valentino, Maria Lucia; La Morgia, Chiara; Liguori, Rocco; Zanna, Claudia; Barboni, Piero; De Nardo, Vera; Martinuzzi, Andrea; Rizzo, Giovanni; Tonon, Caterina; Lodi, Raffaele; Calvaruso, Maria Antonietta; Cappelletti, Martina; Porcelli, Anna Maria; Achilli, Alessandro; Pala, Maria; Torroni, Antonio; Carelli, Valerio

    2013-01-01

    Complex I (CI) deficiency is a frequent cause of mitochondrial disorders and, in most cases, is due to mutations in CI subunit genes encoded by mitochondrial DNA (mtDNA). In this study, we establish the pathogenic role of the heteroplasmic mtDNA m.3890G>A/MT-ND1 (p.R195Q) mutation, which affects an extremely conserved amino acid position in ND1 subunit of CI. This mutation was found in a young-adult male with optic atrophy resembling Leber's hereditary optic neuropathy (LHON) and bilateral brainstem lesions. The only previously reported case with this mutation was a girl with fatal infantile Leigh syndrome with bilateral brainstem lesions. Transfer of the mutant mtDNA in the cybrid cell system resulted in a marked reduction of CI activity and CI-dependent ATP synthesis in the presence of a normally assembled enzyme. These findings establish the pathogenicity of the m.3890G>A/MT-ND1 mutation and remark the link between CI mutations affecting the mtDNA-encoded ND subunits and LHON-like optic atrophy, which may be complicated by bilateral and symmetric lesions affecting the central nervous system. Peculiar to this mutation is the distribution of the brainstem lesions, with sparing of the striatum in both patients. PMID:23246842

  7. Evolution of Bombina bombina and Bombina variegata (Anura: Discoglossidae) in the Carpathian Basin: a history of repeated mt-DNA introgression across species.

    PubMed

    Vörös, Judit; Alcobendas, Marina; Martínez-Solano, Iñigo; García-París, Mario

    2006-03-01

    The structure and geographic location of hybrid zones change through time. Current patterns result from present and historical population-environment interactions that act on each of the hybridizing taxa. This is particularly evident for species involved in complex hybrid zones, such as that formed by the toad species Bombina bombina and Bombina variegata (Anura: Discoglossidae), which interact along extensive areas in Central Europe. We used data on external morphology and partial sequences of the cytochrome oxidase I (cox1) and nicotinamide adenine dinucleotid dehydrogenase subunit 4 (nad4) mitochondrial DNA (mt-DNA) genes to analyze the current patterns of genetic structure shown by both species of Bombina along their contact zone in Hungary. Phylogenetic, phylogeographic, and historical demography analyses were applied to 1.5kb mt-DNA obtained from 119 individuals representing 24 populations from Hungary and additional specimens from Slovakia, Albania, and Bosnia-Herzegovina. We use these data to infer the evolutionary history of the isolated populations of B. variegata in Hungary and to discriminate between competing biogeographic scenarios accounting for the historical interactions between species in this region. Results from the inferred phylogenetic branching pattern and sequence divergence among species and populations support the following: (i) recent population expansion has occurred in Hungarian populations of B. bombina, which are genetically very homogeneous; (ii) the Hungarian populations of B. variegata correspond to two distinct mitochondrial lineages (Carpathian and Alpine, respectively); average maximum-likelihood-corrected sequence divergence between these lineages is 8.96% for cox1 and 10.85% for nad4; (iii) mt-DNA divergence among the three isolated western populations of B. variegata from Transdanubia is low, with four closely related haplotypes, which suggests that the isolation between these populations is the result of a recent process

  8. Human Retinal Transmitochondrial Cybrids with J or H mtDNA Haplogroups Respond Differently to Ultraviolet Radiation: Implications for Retinal Diseases

    PubMed Central

    Malik, Deepika; Hsu, Tiffany; Falatoonzadeh, Payam; Cáceres-del-Carpio, Javier; Tarek, Mohamed; Chwa, Marilyn; Atilano, Shari R.; Ramirez, Claudio; Nesburn, Anthony B.; Boyer, David S.; Kuppermann, Baruch D.; Jazwinski, S. Michal; Miceli, Michael V.; Wallace, Douglas C.; Udar, Nitin; Kenney, M. Cristina

    2014-01-01

    Background It has been recognized that cells do not respond equally to ultraviolet (UV) radiation but it is not clear whether this is due to genetic, biochemical or structural differences of the cells. We have a novel cybrid (cytoplasmic hybrids) model that allows us to analyze the contribution of mitochondrial DNA (mtDNA) to cellular response after exposure to sub-lethal dose of UV. mtDNA can be classified into haplogroups as defined by accumulations of specific single nucleotide polymorphisms (SNPs). Recent studies have shown that J haplogroup is high risk for age-related macular degeneration while the H haplogroup is protective. This study investigates gene expression responses in J cybrids versus H cybrids after exposure to sub-lethal doses of UV-radiation. Methodology/Principal Findings Cybrids were created by fusing platelets isolated from subjects with either H (n = 3) or J (n = 3) haplogroups with mitochondria-free (Rho0) ARPE-19 cells. The H and J cybrids were cultured for 24 hours, treated with 10 mJ of UV-radiation and cultured for an additional 120 hours. Untreated and treated cybrids were analyzed for growth rates and gene expression profiles. The UV-treated and untreated J cybrids had higher growth rates compared to H cybrids. Before treatment, J cybrids showed lower expression levels for CFH, CD55, IL-33, TGF-A, EFEMP-1, RARA, BCL2L13 and BBC3. At 120 hours after UV-treatment, the J cybrids had decreased CFH, RARA and BBC3 levels but increased CD55, IL-33 and EFEMP-1 compared to UV-treated H cybrids. Conclusion/Significance In cells with identical nuclei, the cellular response to sub-lethal UV-radiation is mediated in part by the mtDNA haplogroup. This supports the hypothesis that differences in growth rates and expression levels of complement, inflammation and apoptosis genes may result from population-specific, hereditary SNP variations in mtDNA. Therefore, when analyzing UV-induced damage in tissues, the mtDNA haplogroup background may be

  9. Phylogenetic analysis between domestic and wild duck species in Korea using mtDNA D-loop sequences.

    PubMed

    Jin, S D; Hoque, Md R; Seo, D W; Paek, W K; Kang, T H; Kim, H K; Lee, J H

    2014-03-01

    Recently, the consumption of duck meat has increased; therefore, we need to reveal the origin and gene flow of domestic ducks in Korea. In order to discriminate between duck species, D-loop variations in mitochondrial DNA (mtDNA) have been investigated. In this study, 45 individuals from seven species of wild and domestic ducks in Korea were considered for the D-loop region sequences. With the participation of all the sequences, a phylogenetic neighbor-joining tree was constructed to differentiate between the wild and domestic duck species. In consideration of these sequences, a total 66 haplotypes were obtained (indel included) with an average haplotype of 76.9%, and a haplotype and nucleotide diversity of 0.91 and 0.01, respectively. Also, an estimation of the sequence divergence within and between species was measured in 0.045 and 0.013-0.095, respectively. Meanwhile, the lowest distances of 0.024, 0.013 and 0.018 were observed in three species, including the Mallard, Spot-billed and domestic duck, respectively, which have relatively close genetic relationships. All haplotypes were used for the median-joining network analysis to differentiate all duck species, while three duck species were closely related. Moreover, 26 indel polymorphisms were identified which could be used for the discrimination among the duck species. Based on our results, duck species were effectively discriminated in a D-loop region, which could then be used for an appropriate genetic conservation program for the wild duck and domestic duck breeds in Korea.

  10. Worldwide structure of mtDNA diversity among Cuvier's beaked whales (Ziphius cavirostris): implications for threatened populations.

    PubMed

    Dalebout, Merel L; Robertson, Kelly M; Frantzis, Alexandros; Engelhaupt, Dan; Mignucci-Giannoni, Antonio A; Rosario-Delestre, Raul J; Baker, C Scott

    2005-10-01

    We present the first description of phylogeographic structure among Cuvier's beaked whales (Ziphius cavirostris) worldwide using mitochondrial DNA (mtDNA) control region sequences obtained from strandings (n = 70), incidental fisheries takes (n = 11), biopsy (n = 1), and whale-meat markets (n = 5). Over a 290-base pair fragment, 23 variable sites defined 33 unique haplotypes among the total of 87 samples. Nucleotide diversity at the control region was relatively low (pi = 1.27%+/- 0.723%) compared to wide-ranging baleen whales, but higher than strongly matrifocal sperm, pilot and killer whales. Phylogenetic reconstruction using maximum likelihood revealed four distinct haplotype groups, each of which displayed strong frequency differences among ocean basins, but no reciprocal monophyly or fixed character differences. Consistent with this phylogeographic pattern, an analysis of molecular variance showed high levels of differentiation among ocean basins (F(ST) = 0.14, Phi ST = 0.42; P < 0.001). Estimated rates of female migration among ocean basins were low (generally < or = 2 individuals per generation). Regional sample sizes were too small to detect subdivisions within oceans except in the North Atlantic, where the Mediterranean Sea (n = 12) was highly differentiated due to the presence of two private haplotypes. One market product purchased in South Korea grouped with other haplotypes found only in the North Atlantic, suggesting a violation of current agreements banning international trade in cetacean species. Together, these results demonstrate a high degree of isolation and low maternal gene flow among oceanic, and in some cases, regional populations of Cuvier's beaked whales. This has important implications for understanding the threats of human impact, including fisheries by-catch, direct hunting, and disturbance or mortality from anthropogenic sound.

  11. mtDNA from fossils reveals a radiation of Hawaiian geese recently derived from the Canada goose (Brantacanadensis).

    PubMed

    Paxinos, Ellen E; James, Helen F; Olson, Storrs L; Sorenson, Michael D; Jackson, Jennifer; Fleischer, Robert C

    2002-02-05

    Phylogenetic analysis of 1.35 kb of mtDNA sequence from fossils revealed a previously unknown radiation of Hawaiian geese, of which only one representative remains alive (the endangered Hawaiian goose or nene, Branta sandvicensis). This radiation is nested phylogenetically within a living species, the Canada goose (Branta canadensis) and is related most closely to the large-bodied lineage within that species. The barnacle goose (Branta leucopsis) is also nested within the Canada goose species and is related most closely to the small-bodied lineage of Canada geese. The peripheral isolation of the barnacle goose in the Palearctic apparently allowed the evolution of its distinctive plumage pattern, whereas the two Nearctic lineages of Canada geese share a primitive plumage pattern. The Hawaiian lineage of Canada geese diverged more dramatically, splitting into at least three species that differ in body size, body proportions, and flight ability. One fossil species, limited to the island of Hawaii, was related closely to the nene but was over four times larger, flightless, heavy-bodied and had a much more robust cranium. Application of a rate calibration to levels of DNA divergence suggests that this species evolved on the island of Hawaii in less than 500,000 years. This date is consistent with the potassium/argon-based age of the island of Hawaii of 430,000-500,000 years. The giant Hawaii goose resembles the moa-nalos, a group of massive, extinct, flightless ducks that lived on older Hawaiian Islands and thus is an example of convergent evolution of similar morphologies in island ecosystems.

  12. mtDNA from fossils reveals a radiation of Hawaiian geese recently derived from the Canada goose (Branta canadensis)

    PubMed Central

    Paxinos, Ellen E.; James, Helen F.; Olson, Storrs L.; Sorenson, Michael D.; Jackson, Jennifer; Fleischer, Robert C.

    2002-01-01

    Phylogenetic analysis of 1.35 kb of mtDNA sequence from fossils revealed a previously unknown radiation of Hawaiian geese, of which only one representative remains alive (the endangered Hawaiian goose or nene, Branta sandvicensis). This radiation is nested phylogenetically within a living species, the Canada goose (Branta canadensis) and is related most closely to the large-bodied lineage within that species. The barnacle goose (Branta leucopsis) is also nested within the Canada goose species and is related most closely to the small-bodied lineage of Canada geese. The peripheral isolation of the barnacle goose in the Palearctic apparently allowed the evolution of its distinctive plumage pattern, whereas the two Nearctic lineages of Canada geese share a primitive plumage pattern. The Hawaiian lineage of Canada geese diverged more dramatically, splitting into at least three species that differ in body size, body proportions, and flight ability. One fossil species, limited to the island of Hawaii, was related closely to the nene but was over four times larger, flightless, heavy-bodied and had a much more robust cranium. Application of a rate calibration to levels of DNA divergence suggests that this species evolved on the island of Hawaii in less than 500,000 years. This date is consistent with the potassium/argon-based age of the island of Hawaii of 430,000–500,000 years. The giant Hawaii goose resembles the moa-nalos, a group of massive, extinct, flightless ducks that lived on older Hawaiian Islands and thus is an example of convergent evolution of similar morphologies in island ecosystems. PMID:11818543

  13. Dynamics and phylogenetic implications of MtDNA control region sequences in New World Jays (Aves: Corvidae).

    PubMed

    Saunders, M A; Edwards, S V

    2000-08-01

    To study the evolution of mtDNA and the intergeneric relationships of New World Jays (Aves: Corvidae), we sequenced the entire mitochondrial DNA control region (CR) from 21 species representing all genera of New World jays, an Old World jay, crows, and a magpie. Using maximum likelihood methods, we found that both the transition/transversion ratio (kappa) and among site rate variation (alpha) were higher in flanking domains I and II than in the conserved central domain and that the frequency of indels was highest in domain II. Estimates of kappa and alpha were much more influenced by the density of taxon sampling than by alternative optimal tree topologies. We implemented a successive approximation method incorporating these parameters into phylogenetic analysis. In addition we compared our study in detail to a previous study using cytochrome b and morphology to examine the effect of taxon sampling, evolutionary rates of genes, and combined data on tree resolution. We found that the particular weighting scheme used had no effect on tree topology and little effect on tree robustness. Taxon sampling had a significant effect on tree robustness but little effect on the topology of the best tree. The CR data set differed nonsignificantly from the tree derived from the cytochrome b/morphological data set primarily in the placement of the genus Gymnorhinus, which is near the base of the CR tree. However, contrary to conventional taxonomy, the CR data set suggested that blue and black jays (Cyanocorax sensu lato) might be paraphyletic and that the brown jay Psilorhinus (=Cyanocorax) morio is the sister group to magpie jays (Calocitta), a phylogenetic hypothesis that is likely as parsimonious with regard to nonmolecular characters as monophyly of Cyanocorax. The CR tree also suggests that the common ancestor of NWJs was likely a cooperative breeder. Consistent with recent systematic theory, our data suggest that DNA sequences with high substitution rates such as the CR may

  14. The earliest settlers' antiquity and evolutionary history of Indian populations: evidence from M2 mtDNA lineage

    PubMed Central

    2008-01-01

    Background The "out of Africa" model postulating single "southern route" dispersal posits arrival of "Anatomically Modern Human" to Indian subcontinent around 66–70 thousand years before present (kyBP). However the contributions and legacy of these earliest settlers in contemporary Indian populations, owing to the complex past population dynamics and later migrations has been an issue of controversy. The high frequency of mitochondrial lineage "M2" consistent with its greater age and distribution suggests that it may represent the phylogenetic signature of earliest settlers. Accordingly, we attempted to re-evaluate the impact and contribution of earliest settlers in shaping the genetic diversity and structure of contemporary Indian populations; using our newly sequenced 72 and 4 published complete mitochondrial genomes of this lineage. Results The M2 lineage, harbouring two deep rooting subclades M2a and M2b encompasses approximately one tenth of the mtDNA pool of studied tribes. The phylogeographic spread and diversity indices of M2 and its subclades among the tribes of different geographic regions and linguistic phyla were investigated in detail. Further the reconstructed demographic history of M2 lineage as a surrogate of earliest settlers' component revealed that the demographic events with pronounced regional variations had played pivotal role in shaping the complex net of populations phylogenetic relationship in Indian subcontinent. Conclusion Our results suggest that tribes of southern and eastern region along with Dravidian and Austro-Asiatic speakers of central India are the modern representatives of earliest settlers of subcontinent. The Last Glacial Maximum aridity and post LGM population growth mechanised some sort of homogeneity and redistribution of earliest settlers' component in India. The demic diffusion of agriculture and associated technologies around 3 kyBP, which might have marginalized hunter-gatherer, is coincidental with the decline of

  15. Diversification of sympatric Sapromyza (Diptera: Lauxaniidae) from Madeira: six morphological species but only four mtDNA lineages.

    PubMed

    Pestano, José; Brown, Richard P; Suárez, Nicolás M; Báez, Marcos

    2003-06-01

    A series of recent studies on speciation of insects within the Canary Islands have indicated considerable within-island diversification, similar to that described in the Hawaiian islands. Little work has yet been carried out on the neighboring Madeiran archipelago, which is also volcanic. This study examines relationships among all known Lauxaniid flies of the genus Sapromyza from Madeira (including six newly described morphological species) based on mitochondrial gene trees constructed from cytochrome c oxidase (subunit I) and 16S rRNA partial sequences. Phylogenies based on maximum likelihood distances, a Bayesian method based on Markov chain Monte Carlo sampling from the posterior probability distribution, and maximum parsimony show that eight of the nine Madeiran species comprise a single monophyletic group. This clade is also split into two subclades representing black- and yellow/orange-bodied forms. The latter mtDNA clade corresponds to only two species (Sapromyza imitans and Sapromyza indigena) which are not reciprocally monophyletic. Monophyly is strongly supported within four of the six black-bodied species but not for the species pair (Sapromyza inconspicua, Sapromyza laurisilvae). We discuss the double occurrence (at least) of introgressive hybridization/incomplete lineage sorting within this group and suggest that recent speciation is the most likely explanation. The remaining species on the island, Sapromyza madeirensis, is very divergent from the aforementioned group, occupying a more basal position in the tree than the other Atlantic island and continental Sapromyza that were included in the analysis. At least two speciation events for Madeiran Sapromyza appear to correspond to quite ancient periods relative to the age of the island, while others are more recent. This suggests that a combination of island colonization and within-island sympatric and/or vicariance-mediated speciation may explain the observed diversity.

  16. A mitochondrial retroplasmid integrates into mitochondrial DNA by a novel mechanism involving the synthesis of a hybrid cDNA and homologous recombination.

    PubMed Central

    Chiang, C C; Kennell, J C; Wanner, L A; Lambowitz, A M

    1994-01-01

    The Mauriceville and Varkud mitochondrial plasmids of Neurospora spp. are closely related, small circular DNAs that propagate via an RNA intermediate and reverse transcription. Although the plasmids ordinarily replicate autonomously, they can also integrate into mitochondrial DNA (mtDNA), yielding defective mtDNAs that in some cases cause senescence. To investigate the integration mechanism, we analyzed four cases in which the Varkud plasmid integrated into the mitochondrial small rRNA gene, three in wild-type subcultures and one in a senescent mutant. Our analysis suggests that the integrations occurred by the plasmid reverse transcriptase template switching between the plasmid transcript and internal sequences in the mitochondrial small rRNA to yield hybrid cDNAs that circularized and recombined homologously with the mtDNA. The integrated plasmid sequences are transcribed, presumably from the mitochondrial small rRNA promoters, resulting in hybrid RNAs containing the 5' segment of the mitochondrial small rRNA linked head-to-tail to the full-length plasmid transcript. Analysis of additional senescent mutants revealed three cases in which the plasmid used the same mechanism to integrate at other locations in the mtDNA. In these cases, circular variant plasmids that had incorporated a mitochondrial tRNA or tRNA-like sequence by template switching integrated by homologous recombination at the site of the corresponding tRNA or tRNA-like sequence in mtDNA. This simple integration mechanism involving template switching to generate a hybrid cDNA that integrates homologously could have been used by primitive retroelements prior to the acquisition of a specialized integration machinery. Images PMID:7523850

  17. Reading Mammal Diversity from Flies: The Persistence Period of Amplifiable Mammal mtDNA in Blowfly Guts (Chrysomya megacephala) and a New DNA Mini-Barcode Target

    PubMed Central

    Lee, Ping-Shin; Sing, Kong-Wah; Wilson, John-James

    2015-01-01

    Most tropical mammal species are threatened or data-deficient. Data collection is impeded by the traditional monitoring approaches which can be laborious, expensive and struggle to detect cryptic diversity. Monitoring approaches using mammal DNA derived from invertebrates are emerging as cost- and time-effective alternatives. As a step towards development of blowfly-derived DNA as an effective method for mammal monitoring in the biodiversity hotspot of Peninsular Malaysia, our objectives were (i) to determine the persistence period of amplifiable mammal mtDNA in blowfly guts through a laboratory feeding experiment (ii) to design and test primers that can selectively amplify mammal COI DNA mini-barcodes in the presence of high concentrations of blowfly DNA. The persistence period of amplifiable mammal mtDNA in blowfly guts was 24 h to 96 h post-feeding indicating the need for collecting flies within 24 h of capture to detect mammal mtDNA of sufficient quantity and quality. We designed a new primer combination for a COI DNA mini-barcode that did not amplify blowfly DNA and showed 89% amplification success for a dataset of mammals from Peninsular Malaysia. The short (205 bp) DNA mini-barcode could distinguish most mammal species (including separating dark taxa) and is of suitable length for high-throughput sequencing. Our new DNA mini-barcode target and a standardized trapping protocol with retrieval of blowflies every 24 h could point the way forward in the development of blowfly-derived DNA as an effective method for mammal monitoring. PMID:25898278

  18. A comparative mitogenomic analysis of the potential adaptive value of Arctic charr mtDNA introgression in brook charr populations (Salvelinus fontinalis Mitchill).

    PubMed

    Doiron, Sarah; Bernatchez, Louis; Blier, Pierre U

    2002-11-01

    Wild brook charr populations (Salvelinus fontinalis) completely introgressed with the mitochondrial genome (mtDNA) of arctic charr (Salvelinus alpinus) are found in several lakes of northeastern Québec, Canada. Mitochondrial respiratory enzymes of these populations are thus encoded by their own nuclear DNA and by arctic charr mtDNA. In the present study we performed a comparative sequence analysis of the whole mitochondrial genome of both brook and arctic charr to identify the distribution of mutational differences across these two genomes. This analysis revealed 47 amino acid replacements, 45 of which were confined to subunits of the NADH dehydrogenase complex (Complex I), one in the cox3 gene (Complex IV), and one in the atp8 gene (Complex V). A cladistic approach performed with brook charr, arctic charr, and two other salmonid fishes (rainbow trout [Oncorhynchus mykiss] and Atlantic salmon [Salmo salar]) revealed that only five amino acid replacements were specific to the charr comparison and not shared with the other two salmonids. In addition, five amino acid substitutions localized in the nad2 and nad5 genes denoted negative scores according to the functional properties of amino acids and, therefore, could possibly have an impact on the structure and functional properties of these mitochondrial peptides. The comparison of both brook and arctic charr mtDNA with that of rainbow trout also revealed a relatively constant mutation rate for each specific gene among species, whereas the rate was quite different among genes. This pattern held for both synonymous and nonsynonymous nucleotide positions. These results, therefore, support the hypothesis of selective constraints acting on synonymous codon usage.

  19. Reading Mammal Diversity from Flies: The Persistence Period of Amplifiable Mammal mtDNA in Blowfly Guts (Chrysomya megacephala) and a New DNA Mini-Barcode Target.

    PubMed

    Lee, Ping-Shin; Sing, Kong-Wah; Wilson, John-James

    2015-01-01

    Most tropical mammal species are threatened or data-deficient. Data collection is impeded by the traditional monitoring approaches which can be laborious, expensive and struggle to detect cryptic diversity. Monitoring approaches using mammal DNA derived from invertebrates are emerging as cost- and time-effective alternatives. As a step towards development of blowfly-derived DNA as an effective method for mammal monitoring in the biodiversity hotspot of Peninsular Malaysia, our objectives were (i) to determine the persistence period of amplifiable mammal mtDNA in blowfly guts through a laboratory feeding experiment (ii) to design and test primers that can selectively amplify mammal COI DNA mini-barcodes in the presence of high concentrations of blowfly DNA. The persistence period of amplifiable mammal mtDNA in blowfly guts was 24 h to 96 h post-feeding indicating the need for collecting flies within 24 h of capture to detect mammal mtDNA of sufficient quantity and quality. We designed a new primer combination for a COI DNA mini-barcode that did not amplify blowfly DNA and showed 89% amplification success for a dataset of mammals from Peninsular Malaysia. The short (205 bp) DNA mini-barcode could distinguish most mammal species (including separating dark taxa) and is of suitable length for high-throughput sequencing. Our new DNA mini-barcode target and a standardized trapping protocol with retrieval of blowflies every 24 h could point the way forward in the development of blowfly-derived DNA as an effective method for mammal monitoring.

  20. The evolving male: spinner dolphin (Stenella longirostris) ecotypes are divergent at Y chromosome but not mtDNA or autosomal markers.

    PubMed

    Andrews, Kimberly R; Perrin, William F; Oremus, Marc; Karczmarski, Leszek; Bowen, Brian W; Puritz, Jonathan B; Toonen, Robert J

    2013-05-01

    The susceptibility of the Y chromosome to sexual selection may make this chromosome an important player in the formation of reproductive isolating barriers, and ultimately speciation. Here, we investigate the role of the Y chromosome in phenotypic divergence and reproductive isolation of spinner dolphin (Stenella longirostris) ecotypes. This species contains six known ecotypes (grouped into four subspecies) that exhibit striking differences in morphology, habitat and mating system, despite having adjacent or overlapping ranges and little genetic divergence at previously studied mtDNA and autosomal markers. We examined the phylogeographic structure for all six ecotypes across the species range (n = 261, 17 geographic locations) using DNA sequences from three Y chromosome markers, two maternally inherited mitochondrial (mtDNA) markers, and a biparentally inherited autosomal intron. mtDNA and autosomal analyses revealed low divergence (most Φ(ST) values <0.1) between ecotypes and geographic regions, concordant with previous studies. In contrast, Y intron analyses revealed fixed differences amongst the three most phenotypically divergent groups: S. l. longirostris vs. S. l. roseiventris vs. combined S. l. orientalis/S. l. centroamericana/Tres Marias ecotypes). Another ecotype (whitebelly), previously postulated to be a hybrid between the two phenotypically most divergent ecotypes, had Y haplotypes from both putative parent ecotypes, supporting a hybrid designation. Reduced introgression of the Y chromosome has previously been observed in other organisms ranging from insects to terrestrial mammals, and here we demonstrate this phenomenon in a marine mammal with high dispersal capabilities. These results indicate that reduced introgression of the Y chromosome occurs in a wide taxonomic range of organisms and support the growing body of evidence that rapid evolution of the Y chromosome is important in evolutionary diversification.

  1. Convergence of multiple signaling pathways is required to coordinately up-regulate mtDNA and mitochondrial biogenesis during T cell activation

    PubMed Central

    D’Souza, Anthony D.; Parikh, Neal; Kaech, Susan M.; Shadel, Gerald S.

    2009-01-01

    The quantity and activity of mitochondria vary dramatically in tissues and are modulated in response to changing cellular energy demands and environmental factors. The amount of mitochondrial DNA (mtDNA), which encodes essential subunits of the oxidative phosphorylation complexes required for cellular ATP production, is also tightly regulated, but by largely unknown mechanisms. Using murine T cells as a model system, we have addressed how specific signaling pathways influence mitochondrial biogenesis and mtDNA levels. T cell receptor (TCR) activation results in a large increase in mitochondrial mass and membrane potential and a corresponding increase of mtDNA copy number, indicating the vital role for mitochondrial function for the growth and proliferation of these cells. Independent activation of protein kinase C (via PMA) or calcium-related pathways (via ionomycin) had differential and sub-maximal effects on these mitochondrial parameters, as did activation of naïve T cells with proliferative cytokines. Thus, the robust mitochondrial biogenesis response observed upon TCR activation requires synergy of multiple downstream signaling pathways. One such pathway involves AMP-activated protein kinase (AMPK), which we show has an unprecedented role in negatively regulating mitochondrial biogenesis that is mammalian target of rapamycin (mTOR)-dependent. That is, inhibition of AMPK after TCR signaling commences results in excessive, but uncoordinated mitochondrial proliferation. We propose that mitochondrial biogenesis is not under control of a master regulatory circuit, but rather requires the convergence of multiple signaling pathways with distinct downstream consequences on the organelle’s structure, composition, and function. PMID:17890163

  2. Base composition at mtDNA boundaries suggests a DNA triple helix model for human mitochondrial DNA large-scale rearrangements.

    PubMed

    Rocher, Christophe; Letellier, Thierry; Copeland, William C; Lestienne, Patrick

    2002-06-01

    Different mechanisms have been proposed to account for mitochondrial DNA (mtDNA) instability based on the presence of short homologous sequences (direct repeats, DR) at the potential boundaries of mtDNA rearrangements. Among them, slippage-mispairing of the replication complex during the asymmetric replication cycle of the mammalian mitochondrial DNA has been proposed to account for the preferential localization of deletions. This mechanism involves a transfer of the replication complex from the first neo-synthesized heavy (H) strand of the DR1, to the DR2, thus bypassing the intervening sequence and producing a deleted molecule. Nevertheless, the nature of the bonds between the DNA strands remains unknown as the forward sequence of DR2, beyond the replication complex, stays double-stranded. Here, we have analyzed the base composition of the DR at the boundaries of mtDNA deletions and duplications and found a skewed pyrimidine content of about 75% in the light-strand DNA template. This suggests the possible building of a DNA triple helix between the G-rich neo-synthesized DR1 and the base-paired homologous G.C-rich DR2. In vitro experiments with the purified human DNA polymerase gamma subunits enabled us to show that the third DNA strand may be used as a primer for DNA replication, using a template with the direct repeat forming a hairpin, with which the primer could initiate DNA replication. These data suggest a novel molecular basis for mitochondrial DNA rearrangements through the distributive nature of the DNA polymerase gamma, at the level of the direct repeats. A general model accounting for large-scale mitochondrial DNA deletion and duplication is proposed. These experiments extend to a DNA polymerase from an eucaryote source the use of a DNA triple helix strand as a primer, like other DNA polymerases from phage and bacterial origins.

  3. Development and validation of a D-loop mtDNA SNP assay for the screening of specimens in forensic casework.

    PubMed

    Chemale, Gustavo; Paneto, Greiciane Gaburro; Menezes, Meiga Aurea Mendes; de Freitas, Jorge Marcelo; Jacques, Guilherme Silveira; Cicarelli, Regina Maria Barretto; Fagundes, Paulo Roberto

    2013-05-01

    Mitochondrial DNA (mtDNA) analysis is usually a last resort in routine forensic DNA casework. However, it has become a powerful tool for the analysis of highly degraded samples or samples containing too little or no nuclear DNA, such as old bones and hair shafts. The gold standard methodology still constitutes the direct sequencing of polymerase chain reaction (PCR) products or cloned amplicons from the HVS-1 and HVS-2 (hypervariable segment) control region segments. Identifications using mtDNA are time consuming, expensive and can be very complex, depending on the amount and nature of the material being tested. The main goal of this work is to develop a less labour-intensive and less expensive screening method for mtDNA analysis, in order to aid in the exclusion of non-matching samples and as a presumptive test prior to final confirmatory DNA sequencing. We have selected 14 highly discriminatory single nucleotide polymorphisms (SNPs) based on simulations performed by Salas and Amigo (2010) to be typed using SNaPShot(TM) (Applied Biosystems, Foster City, CA, USA). The assay was validated by typing more than 100 HVS-1/HVS-2 sequenced samples. No differences were observed between the SNP typing and DNA sequencing when results were compared, with the exception of allelic dropouts observed in a few haplotypes. Haplotype diversity simulations were performed using 172 mtDNA sequences representative of the Brazilian population and a score of 0.9794 was obtained when the 14 SNPs were used, showing that the theoretical prediction approach for the selection of highly discriminatory SNPs suggested by Salas and Amigo (2010) was confirmed in the population studied. As the main goal of the work is to develop a screening assay to skip the sequencing of all samples in a particular case, a pair-wise comparison of the sequences was done using the selected SNPs. When both HVS-1/HVS-2 SNPs were used for simulations, at least two differences were observed in 93.2% of the comparisons

  4. Occurrence of Deformed wing virus, Chronic bee paralysis virus and mtDNA variants in haplotype K of Varroa destructor mites in Syrian apiaries.

    PubMed

    Elbeaino, Toufic; Daher-Hjaij, Nouraldin; Ismaeil, Faiz; Mando, Jamal; Khaled, Bassem Solaiman; Kubaa, Raied Abou

    2016-05-01

    A small-scale survey was conducted on 64 beehives located in four governorates of Syria in order to assess for the first time the presence of honeybee-infecting viruses and of Varroa destructor mites in the country. RT-PCR assays conducted on 192 honeybees (Apis mellifera L.) using virus-specific primers showed that Deformed wing virus (DWV) was present in 49 (25.5%) of the tested samples and Chronic bee paralysis virus (CBPV) in 2 (1.04%), whereas Acute bee paralysis virus, Sacbrood virus, Black queen cell virus and Kashmir bee virus were absent. Nucleotide sequences of PCR amplicons obtained from DWV and CBPV genomes shared 95-97 and 100% identity with isolates reported in the GenBank, respectively. The phylogenetic tree grouped the Syrian DWV isolates in one cluster, distinct from all those of different origins reported in the database. Furthermore, 19 adult V. destructor females were genetically analyzed by amplifying and sequencing four fragments in cytochrome oxidase subunit 1 (cox1), ATP synthase 6 (atp6), cox3 and cytochrome b (cytb) mitochondrial DNA (mtDNA) genes. Sequences of concatenated V. destructor mtDNA genes (2696 bp) from Syria were similar to the Korean (K) haplotype and were found recurrently in all governorates. In addition, two genetic lineages of haplotype K with slight variations (0.2-0.3%) were present only in Tartous and Al-Qunaitra governorates.

  5. Genetic diversity in captive and wild Matschie's tree kangaroo (Dendrolagus matschiei) from Huon Peninsula, Papua New Guinea, based on mtDNA control region sequences.

    PubMed

    McGreevy, Thomas J; Dabek, Lisa; Gomez-Chiarri, Marta; Husband, Thomas P

    2009-05-01

    The Association of Zoos and Aquariums (AZA) Matschie's tree kangaroo (Dendrolagus matschiei) population is at a critical point for assessing long-term viability. This population, established from 19 genetically uncharacterized D. matschiei, has endured a founder effect because only four individuals contributed the majority of offspring. The highly variable mitochondrial DNA (mtDNA) control region was sequenced for five of the female-founders by examining extant representatives of their maternal lineage and compared with wild (n = 13) and captive (n = 18) D. matschiei from Papua New Guinea (PNG). AZA female-founder D. matschiei control region haplotype diversity was low, compared with captive D. matschiei held in PNG. AZA D. matschiei have only two control region haplotypes because four out of five AZA female-founder D. matschiei had an identical sequence. Both AZA haplotypes were identified among the 17 wild and captive D. matschiei haplotypes from PNG. Genomic DNA extracted from wild D. matschiei fecal samples was a reliable source of mtDNA that could be used for a larger scale study. We recommend a nuclear DNA genetic analysis to more fully characterize AZA D. matschiei genetic diversity and to assist their Species Survival Plan((R)). An improved understanding of D. matschiei genetics will contribute substantially to the conservation of these unique animals both in captivity and the wild.

  6. Genetic Diversity and Phylogenetic Analysis of South-East Asian Duck Populations Based on the mtDNA D-loop Sequences

    PubMed Central

    Sultana, H.; Seo, D. W.; Bhuiyan, M. S. A.; Choi, N. R.; Hoque, M. R.; Heo, K. N.; Lee, J. H.

    2016-01-01

    The maternally inherited mitochondrial DNA (mtDNA) D–loop region is widely used for exploring genetic relationships and for investigating the origin of various animal species. Currently, domestic ducks play an important role in animal protein supply. In this study, partial mtDNA D–loop sequences were obtained from 145 samples belonging to six South-East Asian duck populations and commercial duck population. All these populations were closely related to the mallard duck (Anas platyrhynchos), as indicated by their mean overall genetic distance. Sixteen nucleotide substitutions were identified in sequence analyses allowing the distinction of 28 haplotypes. Around 42.76% of the duck sequences were classified as Hap_02, which completely matched with Anas platyrhynchos duck species. The neighbor-joining phylogenetic tree also revealed that South-East Asian duck populations were closely related to Anas platyrhynchos. Network profiles were also traced using the 28 haplotypes. Overall, results showed that those duck populations D-loop haplotypes were shared between several duck breeds from Korea and Bangladesh sub continental regions. Therefore, these results confirmed that South-East Asian domestic duck populations have been domesticated from Anas platyrhynchos duck as the maternal origins. PMID:27004808

  7. An mtDNA mutation in the initiation codon of the cytochrome C oxidase subunit II gene results in lower levels of the protein and a mitochondrial encephalomyopathy.

    PubMed Central

    Clark, K M; Taylor, R W; Johnson, M A; Chinnery, P F; Chrzanowska-Lightowlers, Z M; Andrews, R M; Nelson, I P; Wood, N W; Lamont, P J; Hanna, M G; Lightowlers, R N; Turnbull, D M

    1999-01-01

    A novel heteroplasmic 7587T-->C mutation in the mitochondrial genome which changes the initiation codon of the gene encoding cytochrome c oxidase subunit II (COX II), was found in a family with mitochondrial disease. This T-->C transition is predicted to change the initiating methionine to threonine. The mutation load was present at 67% in muscle from the index case and at 91% in muscle from the patient's clinically affected son. Muscle biopsy samples revealed isolated COX deficiency and mitochondrial proliferation. Single-muscle-fiber analysis revealed that the 7587C copy was at much higher load in COX-negative fibers than in COX-positive fibers. After microphotometric enzyme analysis, the mutation was shown to cause a decrease in COX activity when the mutant load was >55%-65%. In fibroblasts from one family member, which contained >95% mutated mtDNA, there was no detectable synthesis or any steady-state level of COX II. This new mutation constitutes a new mechanism by which mtDNA mutations can cause disease-defective initiation of translation. PMID:10205264

  8. Frequent D-loop polymorphism in mtDNA enables genotyping of 1400-year-old human remains from Merowingian graves.

    PubMed

    Zeller, M; Mirghomizadeh, F; Wehner, H D; Blin, N

    2000-01-01

    Improvements of DNA extraction and amplification techniques presently enable DNA analysis of ancient DNA (aDNA) from samples which range from several hundred years of age up to possibly 5000 years. Taking advantage of the abundance of mitochondrial DNA and its polymorphic D-loop sequence, ten individuals from multiple burial sites of the Merowingian culture (South Germany), estimated to be about 1400 years old, were genotyped to determine possible kinship. Moreover, gonosomal DNA markers from the X- and Y-chromosome were applied for sex determination of the remains. In all individuals investigated, deviations from the Anderson mtDNA consensus sequence were observed, all representing substitutions (7 transitions and 3 transversions). Although such mutations have been reported from recent populations, our study constitutes the first description of these mtDNA mutations from numerous aDNA samples recovered from multiple burial sites. The results obtained by molecular anthropology can aid in describing kinship relations and burial customs of ancient remains.

  9. Complete mtDNA of Ciona intestinalis reveals extensive gene rearrangement and the presence of an atp8 and an extra trnM gene in ascidians.

    PubMed

    Gissi, Carmela; Iannelli, Fabio; Pesole, Graziano

    2004-04-01

    The complete mitochondrial genome (mtDNA) of the model organism Ciona intestinalis (Urochordata, Ascidiacea) has been amplified by long-PCR using specific primers designed on putative mitochondrial transcripts identified from publicly available mitochondrial-like expressed sequence tags. The C. intestinalis mtDNA encodes 39 genes: 2 rRNAs, 13 subunits of the respiratory complexes, including ATPase subunit 8 ( atp8), and 24 tRNAs, including 2 tRNA-Met with anticodons 5'-UAU-3'and 5'-CAU-3', respectively. All genes are transcribed from the same strand. This gene content seems to be a common feature of ascidian mtDNAs, as we have verified the presence of a previously undetected atp8 and of two trnM genes in the two other sequenced ascidian mtDNAs. Extensive gene rearrangement has been found in C. intestinalis with respect not only to the common Vertebrata/Cephalochordata/Hemichordata gene organization but also to other ascidian mtDNAs, including the cogeneric Ciona savignyi. Other features such as the absence of long noncoding regions, the shortness of rRNA genes, the low GC content (21.4%), and the absence of asymmetric base distribution between the two strands suggest that this genome is more similar to those of some protostomes than to deuterostomes.

  10. Simultaneous occurrence of the 11778 (ND4) and the 9438 (COX III) mtDNA mutations in Leber hereditary optic neuropathy: Molecular, biochemical, and clinical findings

    SciTech Connect

    Oostra, R.J.; Bleeker-Wagemakers, E.M.; Zwart, R.

    1995-10-01

    Three mtDNA point mutations at nucleotide position (np) 3460, at np 11778 and at np 14484, are thought to be of primary importance in the pathogenesis of Leber hereditary optic neuropathy (LHON), a maternally inherited disease characterized by subacute central vision loss. These mutations are present in genes coding for subunits of complex I (NADH dehydrogenase) of the respiratory chain, occur exclusively in LHON maternal pedigrees, and have never been reported to occur together. Johns and Neufeld postulated that an mtDNA mutation at np 9438, in the gene coding for one of the subunits (COX III) of complex IV (cytochrome c oxidase), was also of primary importance. Johns and Neufeld (1993) found this mutation, which changed a conserved glycine to a serine, in 5 unrelated LHON probands who did not carry one of the presently known primary mutations, but they did not find it in 400 controls. However, the role of this sequence variant has been questioned in the Journal when it has been found to occur in apparently healthy African and Cuban individuals. Subsequently, Johns et al. described this mutation in two Cuban individuals presenting with optic and peripheral neuropathy. 22 refs., 1 fig., 1 tab.

  11. Genetic divergence and phylogenetic relationships in grey mullets (Teleostei: Mugilidae) based on PCR-RFLP analysis of mtDNA segments.

    PubMed

    Papasotiropoulos, V; Klossa-Kilia, E; Kilias, G; Alahiotis, S

    2002-04-01

    The genetic differentiation and phylogenetic relationships among five species of the Mugilidae family (Mugil cephalus, Chelon labrosus, Liza aurata, Liza ramada, and Liza saliens) were investigated at the mtDNA level, on samples taken from Messolongi lagoon-Greece. RFLP analysis of three PCR-amplified mtDNA gene segments (12s rRNA, 16s rRNA, and CO I) was used. Ten, eight, and nine restriction enzymes were found to have at least one recognition site at 12s rRNA, 16s rRNA, and CO I genes, respectively. Several fragment patterns were revealed to be species-specific, and thus they could be useful in species taxonomy as diagnostic markers, as well as for further evolutionary studies. Seven different haplotypes were detected. The greatest amount of genetic differentiation was observed at the interspecific level, while little variation was revealed at the intraspecific level. The highest values of nucleotide sequence divergence were observed between M. cephalus and all the other species, while the lowest was found between C. labrosus and L. saliens. Dendrograms obtained by the three different methods (UPGMA, Neighbor-Joining, and Dollo parsimony), were found to exhibit in all cases the same topology. According to this, the most distinct species is M. cephalus, while the other species are clustered in two separate groups, thefirst one containing L. aurata and L. ramada, the other L. saliens and C. labrosus. This last clustering makes the monophyletic origin of the genus Liza questionable.

  12. Improved health-span and lifespan in mtDNA mutator mice treated with the mitochondrially targeted antioxidant SkQ1

    PubMed Central

    Shabalina, Irina G.; Vyssokikh, Mikhail Yu.; Gibanova, Natalia; Csikasz, Robert I.; Edgar, Daniel; Hallden-Waldemarson, Anne; Rozhdestvenskaya, Zinaida; Bakeeva, Lora E.; Vays, Valeria B.; Pustovidko, Antonina V.; Skulachev, Maxim V.; Cannon, Barbara; Skulachev, Vladimir P.; Nedergaard, Jan

    2017-01-01

    MtDNA mutator mice exhibit marked features of premature aging. We find that these mice treated from age of ≈100 days with the mitochondria-targeted antioxidant SkQ1 showed a delayed appearance of traits of aging such as kyphosis, alopecia, lowering of body temperature, body weight loss, as well as ameliorated heart, kidney and liver pathologies. These effects of SkQ1 are suggested to be related to an alleviation of the effects of an enhanced reactive oxygen species (ROS) level in mtDNA mutator mice: the increased mitochondrial ROS released due to mitochondrial mutations probably interact with polyunsaturated fatty acids in cardiolipin, releasing malondialdehyde and 4-hydroxynonenal that form protein adducts and thus diminishes mitochondrial functions. SkQ1 counteracts this as it scavenges mitochondrial ROS. As the results, the normal mitochondrial ultrastructure is preserved in liver and heart; the phosphorylation capacity of skeletal muscle mitochondria as well as the thermogenic capacity of brown adipose tissue is also improved. The SkQ1-treated mice live significantly longer (335 versus 290 days). These data may be relevant in relation to treatment of mitochondrial diseases particularly and the process of aging in general. PMID:28209927

  13. Investigating the Prehistory of Tungusic Peoples of Siberia and the Amur-Ussuri Region with Complete mtDNA Genome Sequences and Y-chromosomal Markers

    PubMed Central

    Duggan, Ana T.; Whitten, Mark; Wiebe, Victor; Crawford, Michael; Butthof, Anne; Spitsyn, Victor; Makarov, Sergey; Novgorodov, Innokentiy; Osakovsky, Vladimir; Pakendorf, Brigitte

    2013-01-01

    Evenks and Evens, Tungusic-speaking reindeer herders and hunter-gatherers, are spread over a wide area of northern Asia, whereas their linguistic relatives the Udegey, sedentary fishermen and hunter-gatherers, are settled to the south of the lower Amur River. The prehistory and relationships of these Tungusic peoples are as yet poorly investigated, especially with respect to their interactions with neighbouring populations. In this study, we analyse over 500 complete mtDNA genome sequences from nine different Evenk and even subgroups as well as their geographic neighbours from Siberia and their linguistic relatives the Udegey from the Amur-Ussuri region in order to investigate the prehistory of the Tungusic populations. These data are supplemented with analyses of Y-chromosomal haplogroups and STR haplotypes in the Evenks, Evens, and neighbouring Siberian populations. We demonstrate that whereas the North Tungusic Evenks and Evens show evidence of shared ancestry both in the maternal and in the paternal line, this signal has been attenuated by genetic drift and differential gene flow with neighbouring populations, with isolation by distance further shaping the maternal genepool of the Evens. The Udegey, in contrast, appear quite divergent from their linguistic relatives in the maternal line, with a mtDNA haplogroup composition characteristic of populations of the Amur-Ussuri region. Nevertheless, they show affinities with the Evenks, indicating that they might be the result of admixture between local Amur-Ussuri populations and Tungusic populations from the north. PMID:24349531

  14. A new mtDNA mutation in the tRNA[sup Lys] gene associated with myoclonic epilepsy and ragged-red fibers (MERRF)

    SciTech Connect

    Silvestri, G.; Moraes, C.T.; Shanske, S.; DiMauro, S. ); Oh, S.J. )

    1992-12-01

    Myoclonic epilepsy with ragged-red fibers (MERRF) has been associated with an A[r arrow]G transition at mtDNA nt 8344, within a conserved region of the tRNA[sup Lys] gene. Although the 8344 mutation is highly prevalent in patients with MERRF, it is not observed in 10%-20% of the cases, suggesting genetic heterogeneity. The authors have sequenced the tRNA[sup Lys] gene of five MERRF patients lacking the common 8344 mutation. One of these showed a novel T[r arrow]C transition at nucleotide position 8356, disrupting a highly conserved base pair in the T[Psi]C stem. The mutant mtDNA population was essentially homoplasmic in muscle but was heteroplasmic in blood (47%). Neither 20 patients with other mitochondrial diseases nor 25 controls carried this mutation. These findings suggest that tRNA[sup Lys] alterations may play a specific role in the pathogenesis of MERRF syndrome. 21 refs., 4 figs.

  15. Detecting Deep Divergence in Seventeen Populations of Tea Geometrid (Ectropis obliqua Prout) in China by COI mtDNA and Cross-Breeding

    PubMed Central

    Zhang, Chuan-Xi; Yin, Kun-Shan; Tang, Mei-Jun; Guo, Hua-Wei; Fu, Jian-Yu; Xiao, Qiang

    2014-01-01

    The tea geometrid (Ectropis obliqua Prout, Lepidoptera: Geometridae) is a dominant chewing insect endemic in most tea-growing areas in China. Recently some E. obliqua populations have been found to be resistant to the nucleopolyhedrovirus (EoNPV), a host-specific virus that has so far been found only in E. obliqua. Although the resistant populations are morphologically indistinguishable from susceptible populations, we conducted a nationwide collection and examined the genetic divergence in the COI region of the mtDNA in E. obliqua. Phylogenetic analyses of mtDNA in 17 populations revealed two divergent clades with genetic distance greater than 3.7% between clades and less than 0.7% within clades. Therefore, we suggest that E. obliqua falls into two distinct groups. Further inheritance analyses using reciprocal single-pair mating showed an abnormal F1 generation with an unbalanced sex ratio and the inability to produce fertile eggs (or any eggs) through F1 self-crossing. These data revealed a potential cryptic species complex with deep divergence and reproductive isolation within E. obliqua. Uneven distribution of the groups suggests a possible geographic effect on the divergence. Future investigations will be conducted to examine whether EoNPV selection or other factors prompted the evolution of resistance. PMID:24915522

  16. Early population differentiation in extinct aborigines from Tierra del Fuego-Patagonia: ancient mtDNA sequences and Y-chromosome STR characterization.

    PubMed

    García-Bour, Jaume; Pérez-Pérez, Alejandro; Alvarez, Sara; Fernández, Eva; López-Parra, Ana María; Arroyo-Pardo, Eduardo; Turbón, Daniel

    2004-04-01

    Ancient mtDNA was successfully recovered from 24 skeletal samples of a total of 60 ancient individuals from Patagonia-Tierra del Fuego, dated to 100-400 years BP, for which consistent amplifications and two-strand sequences were obtained. Y-chromosome STRs (DYS434, DYS437, DYS439, DYS393, DYS391, DYS390, DYS19, DYS389I, DYS389II, and DYS388) and the biallelic system DYS199 were also amplified, Y-STR alleles could be characterized in nine cases, with an average of 4.1 loci per sample correctly typed. In two samples of the same ethnic group (Aonikenk), an identical and complete eight-loci haplotype was recovered. The DYS199 biallelic system was used as a control of contamination by modern DNA and, along with DYS19, as a marker of American origin. The analysis of both mtDNA and Y-STRs revealed DNA from Amerindian ancestry. The observed polymorphisms are consistent with the hypothesis that the ancient Fuegians are close to populations from south-central Chile and Argentina, but their high nucleotide diversity and the frequency of single lineages strongly support early genetic differentiation of the Fuegians through combined processes of population bottleneck, isolation, and/or migration, followed by strong genetic drift. This suggests an early genetic diversification of the Fuegians right after their arrival at the southernmost extreme of South America.

  17. Less pollen-mediated gene flow for more signatures of glacial lineages: congruent evidence from balsam fir cpDNA and mtDNA for multiple refugia in eastern and central North America.

    PubMed

    Cinget, Benjamin; Gérardi, Sébastien; Beaulieu, Jean; Bousquet, Jean

    2015-01-01

    The phylogeographic structure and postglacial history of balsam fir (Abies balsamea), a transcontinental North American boreal conifer, was inferred using mitochondrial DNA (mtDNA) and chloroplast DNA (cpDNA) markers. Genetic structure among 107 populations (mtDNA data) and 75 populations (cpDNA data) was analyzed using Bayesian and genetic distance approaches. Population differentiation was high for mtDNA (dispersed by seeds only), but also for cpDNA (dispersed by seeds and pollen), indicating that pollen gene flow is more restricted in balsam fir than in other boreal conifers. Low cpDNA gene flow in balsam fir may relate to low pollen production due to the inherent biology of the species and populations being decimated by recurrent spruce budworm epidemics, and/or to low dispersal of pollen grains due to their peculiar structural properties. Accordingly, a phylogeographic structure was detected using both mtDNA and cpDNA markers and population structure analyses supported the existence of at least five genetically distinct glacial lineages in central and eastern North America. Four of these would originate from glacial refugia located south of the Laurentide ice sheet, while the last one would have persisted in the northern Labrador region. As expected due to reduced pollen-mediated gene flow, congruence between the geographic distribution of mtDNA and cpDNA lineages was higher than in other North American conifers. However, concordance was not complete, reflecting that restricted but nonetheless detectable cpDNA gene flow among glacial lineages occurred during the Holocene. As a result, new cpDNA and mtDNA genome combinations indicative of cytoplasmic genome capture were observed.

  18. Less Pollen-Mediated Gene Flow for More Signatures of Glacial Lineages: Congruent Evidence from Balsam Fir cpDNA and mtDNA for Multiple Refugia in Eastern and Central North America

    PubMed Central

    Cinget, Benjamin; Gérardi, Sébastien; Beaulieu, Jean; Bousquet, Jean

    2015-01-01

    The phylogeographic structure and postglacial history of balsam fir (Abies balsamea), a transcontinental North American boreal conifer, was inferred using mitochondrial DNA (mtDNA) and chloroplast DNA (cpDNA) markers. Genetic structure among 107 populations (mtDNA data) and 75 populations (cpDNA data) was analyzed using Bayesian and genetic distance approaches. Population differentiation was high for mtDNA (dispersed by seeds only), but also for cpDNA (dispersed by seeds and pollen), indicating that pollen gene flow is more restricted in balsam fir than in other boreal conifers. Low cpDNA gene flow in balsam fir may relate to low pollen production due to the inherent biology of the species and populations being decimated by recurrent spruce budworm epidemics, and/or to low dispersal of pollen grains due to their peculiar structural properties. Accordingly, a phylogeographic structure was detected using both mtDNA and cpDNA markers and population structure analyses supported the existence of at least five genetically distinct glacial lineages in central and eastern North America. Four of these would originate from glacial refugia located south of the Laurentide ice sheet, while the last one would have persisted in the northern Labrador region. As expected due to reduced pollen-mediated gene flow, congruence between the geographic distribution of mtDNA and cpDNA lineages was higher than in other North American conifers. However, concordance was not complete, reflecting that restricted but nonetheless detectable cpDNA gene flow among glacial lineages occurred during the Holocene. As a result, new cpDNA and mtDNA genome combinations indicative of cytoplasmic genome capture were observed. PMID:25849816

  19. Development and validation of a mtDNA multiplex PCR for identification and discrimination of Calicophoron daubneyi and Fasciola hepatica in the Galba truncatula snail.

    PubMed

    Martínez-Ibeas, A M; González-Warleta, M; Martínez-Valladares, M; Castro-Hermida, J A; González-Lanza, C; Miñambres, B; Ferreras, C; Mezo, M; Manga-González, M Y

    2013-07-01

    Paramphistomosis and Fasciolosis caused by Calicophoron daubneyi and Fasciola hepatica, respectively, are frequent and important trematodoses in ruminant livestock worldwide. Both parasites use the same snail, Galba truncatula, as intermediate host. The aim of this study was to develop and validate an analytical method based on a mitochondrial DNA (mtDNA) multiplex PCR technique which would allow the early and specific identification, in one step, of C. daubneyi and F. hepatica infection in G. truncatula. First of all, a 1035 bp fragment of mtDNA from adult C. daubneyi worms was obtained. Then two pairs of specific mtDNA primers, which amplified a DNA fragment of 885 pb in the case of C. daubneyi, and of 425 pb in that of F. hepatica, were designed. By means of the multiplex PCR technique developed, there was always a specific amplification in samples from adult F. hepatica and C. daubneyi, but not from Calicophoron calicophorum, Cotylophoron cotylophorum, Cotylophoron batycotyle or Dicrocoelium dendriticum. Likewise, specific amplifications of the expected DNA fragments happened in all samples from snails harbouring larval stages of C. daubneyi or F. hepatica, previously detected by microscopy. However, amplifications were not seen when DNA from snails harbouring other Digenea (Plagiorchiidae, Notocotylidae and furcocercous cercariae) was analysed. Moreover, DNA from G. truncatula molluscs free from infection was not amplified. The multiplex PCR assay permitted infection in the snails experimentally infected with 4 miracidia to be detected as early as day 1 p.i. in the case of F. hepatica and with only 2 miracidia from day 2 p.i. in both, C. daubneyi and F. hepatica. Nevertheless it was necessary to wait until days 29 and 33 p.i. to see C. daubneyi and F. hepatica immature redia, respectively, using microscope techniques. The detection limit of the PCR technique was very low: 0.1 ng of DNA from C. daubneyi and 0.001 ng of DNA from F. hepatica. This allowed

  20. Cerebellar hypoplasia and brainstem thinning associated with severe white matter and basal ganglia abnormalities in a child with an mtDNA deletion.

    PubMed

    Biancheri, Roberta; Bruno, Claudio; Cassandrini, Denise; Bertini, Enrico; Santorelli, Filippo M; Rossi, Andrea

    2011-12-01

    Cerebellar and brainstem hypoplasia may occur in different conditions, including those disorders designated as pontocerebellar hypoplasia (PCH). In particular, when PCH is combined with severe supratentorial white matter involvement and cerebral atrophy, mutations in the mitochondrial arginyl-tRNA synthethase (RARS2) gene causing PCH6 are possible. We describe a patient with a lethal mitochondrial encephalomyopathy due to a mtDNA deletion and no alterations in RARS2, whose magnetic resonance (MR) findings mimicked PCH6. A thorough diagnostic work-up for mitochondrial disorders should be carried out when facing with a PCH-like and severe white matter and basal ganglia involvement on brain MR imaging in children, even if clinical and laboratory mitochondrial "stigmata" are scant or nonspecific.

  1. The Molecular Dissection of mtDNA Haplogroup H Confirms That the Franco-Cantabrian Glacial Refuge Was a Major Source for the European Gene Pool

    PubMed Central

    Achilli, Alessandro; Rengo, Chiara; Magri, Chiara; Battaglia, Vincenza; Olivieri, Anna; Scozzari, Rosaria; Cruciani, Fulvio; Zeviani, Massimo; Briem, Egill; Carelli, Valerio; Moral, Pedro; Dugoujon, Jean-Michel; Roostalu, Urmas; Loogväli, Eva-Liis; Kivisild, Toomas; Bandelt, Hans-Jürgen; Richards, Martin; Villems, Richard; Santachiara-Benerecetti, A. Silvana; Semino, Ornella; Torroni, Antonio

    2004-01-01

    Complete sequencing of 62 mitochondrial DNAs (mtDNAs) belonging (or very closely related) to haplogroup H revealed that this mtDNA haplogroup—by far the most common in Europe—is subdivided into numerous subhaplogroups, with at least 15 of them (H1–H15) identifiable by characteristic mutations. All the haplogroup H mtDNAs found in 5,743 subjects from 43 populations were then screened for diagnostic markers of subhaplogroups H1 and H3. This survey showed that both subhaplogroups display frequency peaks, centered in Iberia and surrounding areas, with distributions declining toward the northeast and southeast—a pattern extremely similar to that previously reported for mtDNA haplogroup V. Furthermore, the coalescence ages of H1 and H3 (∼11,000 years) are close to that previously reported for V. These findings have major implications for the origin of Europeans, since they attest that the Franco-Cantabrian refuge area was indeed the source of late-glacial expansions of hunter-gatherers that repopulated much of Central and Northern Europe from ∼15,000 years ago. This has also some implications for disease studies. For instance, the high occurrence of H1 and H3 in Iberia led us to re-evaluate the haplogroup distribution in 50 Spanish families affected by nonsyndromic sensorineural deafness due to the A1555G mutation. The survey revealed that the previously reported excess of H among these families is caused entirely by H3 and is due to a major, probably nonrecent, founder event. PMID:15382008

  2. An mtDNA analysis in ancient Basque populations: implications for haplogroup V as a marker for a major paleolithic expansion from southwestern europe.

    PubMed Central

    Izagirre, N; de la Rúa, C

    1999-01-01

    mtDNA sequence variation was studied in 121 dental samples from four Basque prehistoric sites, by high-resolution RFLP analysis. The results of this study are corroborated by (1) parallel analysis of 92 bone samples, (2) the use of controls during extraction and amplification, and (3) typing by both positive and negative restriction of the linked sites that characterize each haplogroup. The absence of haplogroup V in the prehistoric samples analyzed conflicts with the hypothesis proposed by Torroni et al., in which haplogroup V is considered as an mtDNA marker for a major Paleolithic population expansion from southwestern Europe, occurring approximately 10,000-15,000 years before the present (YBP). Our samples from the Basque Country provide a valuable tool for checking the previous hypothesis, which is based on genetic data from present-day populations. In light of the available data, the most realistic scenario to explain the origin and distribution of haplogroup V suggests that the mutation defining that haplogroup (4577 NlaIII) appeared at a time when the effective population size was small enough to allow genetic drift to act-and that such drift is responsible for the heterogeneity observed in Basques, with regard to the frequency of haplogroup V (0%-20%). This is compatible with the attributed date for the origin of that mutation (10,000-15, 000 YBP), because during the postglacial period (the Mesolithic, approximately 11,000 YBP) there was a major demographic change in the Basque Country, which minimized the effect of genetic drift. This interpretation does not rely on migratory movements to explain the distribution of haplogroup V in present-day Indo-European populations. PMID:10364533

  3. Peeking through the trapdoor: Historical biogeography of the Aegean endemic spider Cyrtocarenum Ausserer, 1871 with an estimation of mtDNA substitution rates for Mygalomorphae.

    PubMed

    Kornilios, P; Thanou, E; Kapli, P; Parmakelis, A; Chatzaki, M

    2016-05-01

    The Aegean region, located in the Eastern Mediterranean, is an area of rich biodiversity and endemism. Its position, geographical configuration and complex geological history have shaped the diversification history of many animal taxa. Mygalomorph spiders have drawn the attention of researchers, as excellent model systems for phylogeographical investigations. However, phylogeographic studies of spiders in the Aegean region are scarce. In this study, we focused on the phylogeography of the endemic ctenizid trap-door spider Cyrtocarenum Ausserer, 1871. The genus includes two morphologically described species: C. grajum (C.L. Koch, 1836) and C. cunicularium (Olivier, 1811). We sampled 60 specimens from the distributions of both species and analyzed four mitochondrial and two nuclear markers. Cyrtocarenum served as an example to demonstrate the importance of natural history traits in the inference of phylogeographic scenarios. The mtDNA substitution rates inferred for the genus are profoundly higher compared to araneomorph spiders and other arthropods, which seems tightly associated with their biology. We evaluate published mtDNA substitution rates followed in the literature for mygalomorph spiders and discuss potential pitfalls. Following gene tree (maximum likelihood, Bayesian inference) and species tree approaches ((*)BEAST), we reconstructed a time-calibrated phylogeny of the genus. These results, combined with a biogeographical ancestral-area analysis, helped build a biogeographic scenario that describes how the major palaeogeographic and palaeoclimatic events of the Aegean may have affected the distribution of Cyrtocarenum lineages. The diversification of the genus seems to have begun in the Middle Miocene in the present west Aegean area, while major phylogenetic events occurred at the Miocene-Pliocene boundary for C. cunicularium, probably related to the Messinian Salinity Crisis. Our results also demonstrate the clear molecular distinction of the two

  4. MtDNA Haplogroup A10 Lineages in Bronze Age Samples Suggest That Ancient Autochthonous Human Groups Contributed to the Specificity of the Indigenous West Siberian Population

    PubMed Central

    Pilipenko, Aleksandr S.; Trapezov, Rostislav O.; Zhuravlev, Anton A.; Molodin, Vyacheslav I.; Romaschenko, Aida G.

    2015-01-01

    Background The craniometric specificity of the indigenous West Siberian human populations cannot be completely explained by the genetic interactions of the western and eastern Eurasian groups recorded in the archaeology of the area from the beginning of the 2nd millennium BC. Anthropologists have proposed another probable explanation: contribution to the genetic structure of West Siberian indigenous populations by ancient human groups, which separated from western and eastern Eurasian populations before the final formation of their phenotypic and genetic features and evolved independently in the region over a long period of time. This hypothesis remains untested. From the genetic point of view, it could be confirmed by the presence in the gene pool of indigenous populations of autochthonous components that evolved in the region over long time periods. The detection of such components, particularly in the mtDNA gene pool, is crucial for further clarification of early regional genetic history. Results and Conclusion We present the results of analysis of mtDNA samples (n = 10) belonging to the A10 haplogroup, from Bronze Age populations of West Siberian forest-steppe (V—I millennium BC), that were identified in a screening study of a large diachronic sample (n = 96). A10 lineages, which are very rare in modern Eurasian populations, were found in all the Bronze Age groups under study. Data on the A10 lineages’ phylogeny and phylogeography in ancient West Siberian and modern Eurasian populations suggest that A10 haplogroup underwent a long-term evolution in West Siberia or arose there autochthonously; thus, the presence of A10 lineages indicates the possible contribution of early autochthonous human groups to the genetic specificity of modern populations, in addition to contributions of later interactions of western and eastern Eurasian populations. PMID:25950581

  5. The expanded mtDNA phylogeny of the Franco-Cantabrian region upholds the pre-neolithic genetic substrate of Basques.

    PubMed

    Cardoso, Sergio; Valverde, Laura; Alfonso-Sánchez, Miguel A; Palencia-Madrid, Leire; Elcoroaristizabal, Xabier; Algorta, Jaime; Catarino, Susana; Arteta, David; Herrera, Rene J; Zarrabeitia, María Teresa; Peña, José A; de Pancorbo, Marian M

    2013-01-01

    The European genetic landscape has been shaped by several human migrations occurred since Paleolithic times. The accumulation of archaeological records and the concordance of different lines of genetic evidence during the last two decades have triggered an interesting debate concerning the role of ancient settlers from the Franco-Cantabrian region in the postglacial resettlement of Europe. Among the Franco-Cantabrian populations, Basques are regarded as one of the oldest and more intriguing human groups of Europe. Recent data on complete mitochondrial DNA genomes focused on macrohaplogroup R0 revealed that Basques harbor some autochthonous lineages, suggesting a genetic continuity since pre-Neolithic times. However, excluding haplogroup H, the most representative lineage of macrohaplogroup R0, the majority of maternal lineages of this area remains virtually unexplored, so that further refinement of the mtDNA phylogeny based on analyses at the highest level of resolution is crucial for a better understanding of the European prehistory. We thus explored the maternal ancestry of 548 autochthonous individuals from various Franco-Cantabrian populations and sequenced 76 mitogenomes of the most representative lineages. Interestingly, we identified three mtDNA haplogroups, U5b1f, J1c5c1 and V22, that proved to be representative of Franco-Cantabria, notably of the Basque population. The seclusion and diversity of these female genetic lineages support a local origin in the Franco-Cantabrian area during the Mesolithic of southwestern Europe, ~10,000 years before present (YBP), with signals of expansions at ~3,500 YBP. These findings provide robust evidence of a partial genetic continuity between contemporary autochthonous populations from the Franco-Cantabrian region, specifically the Basques, and Paleolithic/Mesolithic hunter-gatherer groups. Furthermore, our results raise the current proportion (≈ 15%) of the Franco-Cantabrian maternal gene pool with a putative pre

  6. mtDNA diversity in Chukchi and Siberian Eskimos: implications for the genetic history of Ancient Beringia and the peopling of the New World.

    PubMed Central

    Starikovskaya, Y B; Sukernik, R I; Schurr, T G; Kogelnik, A M; Wallace, D C

    1998-01-01

    The mtDNAs of 145 individuals representing the aboriginal populations of Chukotka-the Chukchi and Siberian Eskimos-were subjected to RFLP analysis and control-region sequencing. This analysis showed that the core of the genetic makeup of the Chukchi and Siberian Eskimos consisted of three (A, C, and D) of the four primary mtDNA haplotype groups (haplogroups) (A-D) observed in Native Americans, with haplogroup A being the most prevalent in both Chukotkan populations. Two unique haplotypes belonging to haplogroup G (formerly called "other" mtDNAs) were also observed in a few Chukchi, and these have apparently been acquired through gene flow from adjacent Kamchatka, where haplogroup G is prevalent in the Koryak and Itel'men. In addition, a 16111C-->T transition appears to delineate an "American" enclave of haplogroup A mtDNAs in northeastern Siberia, whereas the 16192C-->T transition demarcates a "northern Pacific Rim" cluster within this haplogroup. Furthermore, the sequence-divergence estimates for haplogroups A, C, and D of Siberian and Native American populations indicate that the earliest inhabitants of Beringia possessed a limited number of founding mtDNA haplotypes and that the first humans expanded into the New World approximately 34,000 years before present (YBP). Subsequent migration 16,000-13,000 YBP apparently brought a restricted number of haplogroup B haplotypes to the Americas. For millennia, Beringia may have been the repository of the respective founding sequences that selectively penetrated into northern North America from western Alaska. PMID:9792876

  7. An mtDNA analysis in ancient Basque populations: implications for haplogroup V as a marker for a major paleolithic expansion from southwestern europe.

    PubMed

    Izagirre, N; de la Rúa, C

    1999-07-01

    mtDNA sequence variation was studied in 121 dental samples from four Basque prehistoric sites, by high-resolution RFLP analysis. The results of this study are corroborated by (1) parallel analysis of 92 bone samples, (2) the use of controls during extraction and amplification, and (3) typing by both positive and negative restriction of the linked sites that characterize each haplogroup. The absence of haplogroup V in the prehistoric samples analyzed conflicts with the hypothesis proposed by Torroni et al., in which haplogroup V is considered as an mtDNA marker for a major Paleolithic population expansion from southwestern Europe, occurring approximately 10,000-15,000 years before the present (YBP). Our samples from the Basque Country provide a valuable tool for checking the previous hypothesis, which is based on genetic data from present-day populations. In light of the available data, the most realistic scenario to explain the origin and distribution of haplogroup V suggests that the mutation defining that haplogroup (4577 NlaIII) appeared at a time when the effective population size was small enough to allow genetic drift to act-and that such drift is responsible for the heterogeneity observed in Basques, with regard to the frequency of haplogroup V (0%-20%). This is compatible with the attributed date for the origin of that mutation (10,000-15, 000 YBP), because during the postglacial period (the Mesolithic, approximately 11,000 YBP) there was a major demographic change in the Basque Country, which minimized the effect of genetic drift. This interpretation does not rely on migratory movements to explain the distribution of haplogroup V in present-day Indo-European populations.

  8. The effect of overexpression of PGC-1α on the mtDNA4834 common deletion in a rat cochlear marginal cell senescence model.

    PubMed

    Zhao, Xue-Yan; Sun, Jin-Li; Hu, Yu-Juan; Yang, Yang; Zhang, Wen-Juan; Hu, Yuan; Li, Jun; Sun, Yu; Zhong, Yi; Peng, Wei; Zhang, Hong-Lian; Kong, Wei-Jia

    2013-02-01

    Aging is a natural process usually defined as a progressive loss of function with an accumulation of senescent cells. The clinical manifestations of this process include age-related hearing loss (AHL)/presbycusis. Several investigations indicated the association between a mitochondrial common deletion (CD) (mtDNA 4977-bp deletion in humans, corresponding to 4834-bp deletion in rats) and presbycusis. Previous researches have shown that peroxisome proliferator-activated receptor-gamma coactivator-1α (PGC-1α) is a key regulator of mitochondrial biogenesis and energy metabolism. However, the expression of PGC-1α in the inner ear and the possible effect of PGC-1α on presbycusis are not clear. Our data demonstrated the distribution of PGC-1α and its downstream transcription factors nuclear respiratory factor-1 (NRF-1), mitochondrial transcription factor A (Tfam) and nuclear factor κB (NF-κB) in marginal cells (MCs) for the first time. To explore the role of PGC-1α in cellular senescence, we established a model of marginal cell senescence harboring the mtDNA4834 common deletion induced by d-galactose. We also found that PGC-1α and its downstream transcription factors compensatorily increased in our cell senescence model. Furthermore, the overexpression of PGC-1α induced by transfection largely increased the expression levels of NRF-1 and TFAM and significantly decreased the expression level of NF-κB in the cell senescence model. And the levels of CD, senescent cells and apoptotic cells in the cell model decreased after PGC-1α overexpression. These results suggested that PGC-1α might protect MCs in this cell model from senescence through a nuclear-mitochondrial interaction and against apoptosis. Our study may shed light on the pathogenesis of presbycusis and provide a new therapeutic target for presbycusis.

  9. Genetic variations of ND5 gene of mtDNA in populations of Anopheles sinensis (Diptera: Culicidae) malaria vector in China

    PubMed Central

    2013-01-01

    Background Anopheles sinensis is a principal vector for Plasmodium vivax malaria in most parts of China. Understanding of genetic structure and genetic differentiation of the mosquito should contribute to the vector control and malaria elimination in China. Methods The present study investigated the genetic structure of An. sinensis populations using a 729 bp fragment of mtDNA ND5 among 10 populations collected from seven provinces in China. Results ND5 was polymorphic by single mutations within three groups of An. sinensis that were collected from 10 different geographic populations in China. Out of 140 specimens collected from 10 representative sites, 84 haplotypes and 71 variable positions were determined. The overall level of genetic differentiation of An. sinensis varied from low to moderate across China and with a FST range of 0.00065 – 0.341. Genealogy analysis clustered the populations of An. sinensis into three main clusters. Each cluster shared one main haplotype. Pairwise variations within populations were higher (68.68%) than among populations (31.32%) and with high fixation index (FST = 0.313). The results of the present study support population growth and expansion in the An. sinensis populations from China. Three clusters of An. sinensis populations were detected in this study with each displaying different proportion patterns over seven Chinese provinces. No correlation between genetic and geographic distance was detected in overall populations of An. sinensis (R2 = 0.058; P = 0.301). Conclusions The results indicate that the ND5 gene of mtDNA is highly polymorphic in An. sinensis and has moderate genetic variability in the populations of this mosquito in China. Demographic and spatial results support evidence of expansion in An. sinensis populations. PMID:24192424

  10. Control of mitochondrial integrity in ageing and disease.

    PubMed

    Szklarczyk, Radek; Nooteboom, Marco; Osiewacz, Heinz D

    2014-07-05

    Various molecular and cellular pathways are active in eukaryotes to control the quality and integrity of mitochondria. These pathways are involved in keeping a 'healthy' population of this essential organelle during the lifetime of the organism. Quality control (QC) systems counteract processes that lead to organellar dysfunction manifesting as degenerative diseases and ageing. We discuss disease- and ageing-related pathways involved in mitochondrial QC: mtDNA repair and reorganization, regeneration of oxidized amino acids, refolding and degradation of severely damaged proteins, degradation of whole mitochondria by mitophagy and finally programmed cell death. The control of the integrity of mtDNA and regulation of its expression is essential to remodel single proteins as well as mitochondrial complexes that determine mitochondrial functions. The redundancy of components, such as proteases, and the hierarchies of the QC raise questions about crosstalk between systems and their precise regulation. The understanding of the underlying mechanisms on the genomic, proteomic, organellar and cellular levels holds the key for the development of interventions for mitochondrial dysfunctions, degenerative processes, ageing and age-related diseases resulting from impairments of mitochondria.

  11. Why Mitochondria Must Fuse to Maintain Their Genome Integrity

    PubMed Central

    Vidoni, Sara; Zanna, Claudia; Sarzi, Emmanuelle

    2013-01-01

    Abstract Significance: The maintenance of mitochondrial genome integrity is a major challenge for cells to sustain energy production by respiration. Recent Advances: Recently, mitochondrial membrane dynamics emerged as a key process contributing to prevent mitochondrial DNA (mtDNA) alterations. Indeed, both fundamental and clinical data suggest that disruption of mitochondrial fusion, related to mutations in the OPA1, MFN2, PINK1, and PARK2 genes, leads to the accumulation of mutations in the mitochondrial genome. Critical Issues: We discuss here the possibility that mitochondrial fusion acts as a direct mechanism to prevent the generation of altered mtDNA and to eliminate mutated deleterious genomes either by trans-complementation or by mitophagy. Future Directions: Finally, we conclude this review with a short evolutionary comparison between the mechanisms involved in mitochondrial and bacterial modes of genome distribution and plasticity, highlighting possible common conserved processes required for the maintenance of their genome integrity, which should inspire our future investigations. Antioxid. Redox Signal. 19, 379–388. PMID:23350575

  12. Multiple symmetric lipomas with high levels of mtDNA with the tRNA(Lys) A-->G(8344) mutation as the only manifestation of disease in a carrier of myoclonus epilepsy and ragged-red fibers (MERRF) syndrome.

    PubMed Central

    Holme, E; Larsson, N G; Oldfors, A; Tulinius, M; Sahlin, P; Stenman, G

    1993-01-01

    We have investigated the morphology, cytogenetics, and the fraction of mtDNA with the tRNA(Lys) A-->G(8344) mutation in three lipomas in a carrier of this mutation. The son of the patient had myoclonus epilepsy and ragged-red fibers syndrome. The fraction of mtDNA with the tRNA(Lys) mutation varied between 62% and 80% in cultured skin fibroblasts, lymphocytes, normal adipose tissue, and muscle. In the three lipomas the mean fraction of mutated mtDNA was 90%, 94%, and 94%. Ultrastructural examination of the lipomas revealed numerous mitochondria with changes such as electron-dense inclusions in some adipocytes. When considered cytogenetically, the lipomas were characterized by a mixture of karyotypically abnormal and normal cells. An identical del(6)(q24) was found in two tumors. The fraction of mutated mtDNA in cultured lipoma cells was the same as in the lipoma in situ, indicating that the cultured cells were representative of the primary tumor. These findings indicate that the lipomas have originated with a grossly normal stem line and subsequently have developed the 6q deletion. We conclude that the lipomas represent clonal growth of adipocytes with a high content of mtDNA with the tRNA(Lys) mutation. The tRNA(Lys) mutation may be either the direct or the indirect cause of pertubation of the maturation process of the adipocytes, leading to an increased risk of lipoma formation. Images Figure 1 Figure 2 Figure 3 PMID:8447321

  13. Disrupting Mitochondrial–Nuclear Coevolution Affects OXPHOS Complex I Integrity and Impacts Human Health

    PubMed Central

    Gershoni, Moran; Levin, Liron; Ovadia, Ofer; Toiw, Yasmin; Shani, Naama; Dadon, Sara; Barzilai, Nir; Bergman, Aviv; Atzmon, Gil; Wainstein, Julio; Tsur, Anat; Nijtmans, Leo; Glaser, Benjamin; Mishmar, Dan

    2014-01-01

    The mutation rate of the mitochondrial DNA (mtDNA), which is higher by an order of magnitude as compared with the nuclear genome, enforces tight mitonuclear coevolution to maintain mitochondrial activities. Interruption of such coevolution plays a role in interpopulation hybrid breakdown, speciation events, and disease susceptibility. Previously, we found an elevated amino acid replacement rate and positive selection in the nuclear DNA-encoded oxidative phosphorylation (OXPHOS) complex I subunit NDUFC2, a phenomenon important for the direct interaction of NDUFC2 with the mtDNA-encoded complex I subunit ND4. This finding underlines the importance of mitonuclear coevolution to physical interactions between mtDNA and nuclear DNA-encoded factors. Nevertheless, it remains unclear whether this interaction is important for the stability and activity of complex I. Here, we show that siRNA silencing of NDUFC2 reduced growth of human D-407 retinal pigment epithelial cells, significantly diminished mitochondrial membrane potential, and interfered with complex I integrity. Moreover, site-directed mutagenesis of a positively selected amino acid in NDUFC2 significantly interfered with the interaction of NDUFC2 with its mtDNA-encoded partner ND4. Finally, we show that a genotype combination involving this amino acid (NDUFC2 residue 46) and the mtDNA haplogroup HV likely altered susceptibility to type 2 diabetes mellitus in Ashkenazi Jews. Therefore, mitonuclear coevolution is important for maintaining mitonuclear factor interactions, OXPHOS, and for human health. PMID:25245408

  14. Gauge Integration

    DTIC Science & Technology

    2002-09-01

    convergence theorems. Lebesgue developed his theory of measure and integration to address these shortcomings. His integral is more powerful in the...This relatively recent integral possesses the intuitive description of the Riemann integral, with the power of the Lebesgue integral. The purpose of this...strong convergence theorems. Lebesgue developed his theory of measure and integration to address these shortcomings. His integral is more powerful in the

  15. Integrated Means Integrity

    ERIC Educational Resources Information Center

    Odegard, John D.

    1978-01-01

    Describes the operation of the Cessna Pilot Center (CPC) flight training systems. The program is based on a series of integrated activities involving stimulus, response, reinforcement and association components. Results show that the program can significantly reduce in-flight training time. (CP)

  16. The Expanded mtDNA Phylogeny of the Franco-Cantabrian Region Upholds the Pre-Neolithic Genetic Substrate of Basques

    PubMed Central

    Cardoso, Sergio; Valverde, Laura; Alfonso-Sánchez, Miguel A.; Palencia-Madrid, Leire; Elcoroaristizabal, Xabier; Algorta, Jaime; Catarino, Susana; Arteta, David; Herrera, Rene J.; Zarrabeitia, María Teresa; Peña, José A.; de Pancorbo, Marian M.

    2013-01-01

    The European genetic landscape has been shaped by several human migrations occurred since Paleolithic times. The accumulation of archaeological records and the concordance of different lines of genetic evidence during the last two decades have triggered an interesting debate concerning the role of ancient settlers from the Franco-Cantabrian region in the postglacial resettlement of Europe. Among the Franco-Cantabrian populations, Basques are regarded as one of the oldest and more intriguing human groups of Europe. Recent data on complete mitochondrial DNA genomes focused on macrohaplogroup R0 revealed that Basques harbor some autochthonous lineages, suggesting a genetic continuity since pre-Neolithic times. However, excluding haplogroup H, the most representative lineage of macrohaplogroup R0, the majority of maternal lineages of this area remains virtually unexplored, so that further refinement of the mtDNA phylogeny based on analyses at the highest level of resolution is crucial for a better understanding of the European prehistory. We thus explored the maternal ancestry of 548 autochthonous individuals from various Franco-Cantabrian populations and sequenced 76 mitogenomes of the most representative lineages. Interestingly, we identified three mtDNA haplogroups, U5b1f, J1c5c1 and V22, that proved to be representative of Franco-Cantabria, notably of the Basque population. The seclusion and diversity of these female genetic lineages support a local origin in the Franco-Cantabrian area during the Mesolithic of southwestern Europe, ∼10,000 years before present (YBP), with signals of expansions at ∼3,500 YBP. These findings provide robust evidence of a partial genetic continuity between contemporary autochthonous populations from the Franco-Cantabrian region, specifically the Basques, and Paleolithic/Mesolithic hunter-gatherer groups. Furthermore, our results raise the current proportion (≈15%) of the Franco-Cantabrian maternal gene pool with a putative pre

  17. Stable nuclear expression of ATP8 and ATP6 genes rescues a mtDNA Complex V null mutant

    PubMed Central

    Boominathan, Amutha; Vanhoozer, Shon; Basisty, Nathan; Powers, Kathleen; Crampton, Alexandra L.; Wang, Xiaobin; Friedricks, Natalie; Schilling, Birgit; Brand, Martin D.; O'Connor, Matthew S.

    2016-01-01

    We explore the possibility of re-engineering mitochondrial genes and expressing them from the nucleus as an approach to rescue defects arising from mitochondrial DNA mutations. We have used a patient cybrid cell line with a single point mutation in the overlap region of the ATP8 and ATP6 genes of the human mitochondrial genome. These cells are null for the ATP8 protein, have significantly lowered ATP6 protein levels and no Complex V function. Nuclear expression of only the ATP8 gene with the ATP5G1 mitochondrial targeting sequence appended restored viability on Krebs cycle substrates and ATP synthesis capabilities but, failed to restore ATP hydrolysis and was insensitive to various inhibitors of oxidative phosphorylation. Co-expressing both ATP8 and ATP6 genes under similar conditions resulted in stable protein expression leading to successful integration into Complex V of the oxidative phosphorylation machinery. Tests for ATP hydrolysis / synthesis, oxygen consumption, glycolytic metabolism and viability all indicate a significant functional rescue of the mutant phenotype (including re-assembly of Complex V) following stable co-expression of ATP8 and ATP6. Thus, we report the stable allotopic expression, import and function of two mitochondria encoded genes, ATP8 and ATP6, resulting in simultaneous rescue of the loss of both mitochondrial proteins. PMID:27596602

  18. Evolutionary analysis of a large mtDNA translocation (numt) into the nuclear genome of the Panthera genus species.

    PubMed

    Kim, Jae-Heup; Antunes, Agostinho; Luo, Shu-Jin; Menninger, Joan; Nash, William G; O'Brien, Stephen J; Johnson, Warren E

    2006-02-01

    Translocation of cymtDNA into the nuclear genome, also referred to as numt, has been reported in many species, including several closely related to the domestic cat (Felis catus). We describe the recent transposition of 12,536 bp of the 17 kb mitochondrial genome into the nucleus of the common ancestor of the five Panthera genus species: tiger, P. tigris; snow leopard, P. uncia; jaguar, P. onca; leopard, P. pardus; and lion, P. leo. This nuclear integration, representing 74% of the mitochondrial genome, is one of the largest to be reported in eukaryotes. The Panthera genus numt differs from the numt previously described in the Felis genus in: (1) chromosomal location (F2-telomeric region vs. D2-centromeric region), (2) gene make up (from the ND5 to the ATP8 vs. from the CR to the COII), (3) size (12.5 vs. 7.9 kb), and (4) structure (single monomer vs. tandemly repeated in Felis). These distinctions indicate that the origin of this large numt fragment in the nuclear genome of the Panthera species is an independent insertion from that of the domestic cat lineage, which has been further supported by phylogenetic analyses. The tiger cymtDNA shared around 90% sequence identity with the homologous numt sequence, suggesting an origin for the Panthera numt at around 3.5 million years ago, prior to the radiation of the five extant Panthera species.

  19. mtDNA from the Early Bronze Age to the Roman Period Suggests a Genetic Link between the Indian Subcontinent and Mesopotamian Cradle of Civilization

    PubMed Central

    Witas, Henryk W.; Tomczyk, Jacek; Jędrychowska-Dańska, Krystyna; Chaubey, Gyaneshwer; Płoszaj, Tomasz

    2013-01-01

    Ancient DNA methodology was applied to analyse sequences extracted from freshly unearthed remains (teeth) of 4 individuals deeply deposited in slightly alkaline soil of the Tell Ashara (ancient Terqa) and Tell Masaikh (ancient Kar-Assurnasirpal) Syrian archaeological sites, both in the middle Euphrates valley. Dated to the period between 2.5 Kyrs BC and 0.5 Kyrs AD the studied individuals carried mtDNA haplotypes corresponding to the M4b1, M49 and/or M61 haplogroups, which are believed to have arisen in the area of the Indian subcontinent during the Upper Paleolithic and are absent in people living today in Syria. However, they are present in people inhabiting today’s Tibet, Himalayas, India and Pakistan. We anticipate that the analysed remains from Mesopotamia belonged to people with genetic affinity to the Indian subcontinent since the distribution of identified ancient haplotypes indicates solid link with populations from the region of South Asia-Tibet (Trans-Himalaya). They may have been descendants of migrants from much earlier times, spreading the clades of the macrohaplogroup M throughout Eurasia and founding regional Mesopotamian groups like that of Terqa or just merchants moving along trade routes passing near or through the region. None of the successfully identified nuclear alleles turned out to be ΔF508 CFTR, LCT-13910T or Δ32 CCR5. PMID:24040024

  20. New ideas about genetic differentiation of Chilo suppressalis (Lepidoptera: Pyralidae) populations in China based on the mtDNA cytochrome b gene.

    PubMed

    Tang, Xiao-Tian; Zheng, Fu-Shan; Lu, Ming-Xing; Du, Yu-Zhou

    2016-01-01

    The striped stem borer, Chilo suppressalis (Walker), is an important pest of rice in China and other parts of the world. To further explore the population genetic structure and genetic differentiation of C. suppressalis populations found on rice in China, we amplified 432 bp fragments of the cytochrome b (cyt b) gene for 44 C. suppressalis populations. Nineteen variable sites in the mtDNA gene were observed, and 16 haplotypes were identified. Nucleotide diversity (π) and haplotype diversity (h) ranged from 0.00274 to 0.00786 and 0.72297 to 0.87604, respectively, while genetic structure analysis found significant genetic differentiation to be present among the five regions in China - northern China (NC), northeastern China (NEC), central China (CC), southern China (SC) and southwestern China (SWC) - where C. suppresalis was collected. In addition, molecular variance (AMOVA) showed that a relatively high proportion (57.6%) of the total genetic variance was attributable to variation within the populations. N(m) and F(ST) analyses suggested that the differentiation was not significantly different between NEC and NC, CC and SC, and SC and SWC regions, but was significant between NEC and CC, SC and SWC regions, corresponding well with the geographical distribution of the sampled populations. Phylogenetic analysis divided the populations into two indistinct clades: a NEC-NC-CC clade and a CC-SC-SWC clade, while CC region acted as a transition zone between north and south China, a finding different from previous work.

  1. Coalescent analysis of mtDNA indicates Pleistocene divergence among three species of howler monkey (Alouatta spp.) and population subdivision within the Atlantic Coastal Forest species, A. guariba.

    PubMed

    de Mello Martins, Felipe; Gifalli-Iughetti, Cristiani; Koiffman, Celia Priszkulnik; Harris, Eugene E

    2011-01-01

    We have used coalescent analysis of mtDNA cytochrome b (cyt b) sequences to estimate times of divergence of three species of Alouatta--A. caraya, A. belzebul, and A. guariba--which are in close geographic proximity. A. caraya is inferred to have diverged from the A. guariba/A. belzebul clade approximately 3.83 million years ago (MYA), with the later pair diverging approximately 1.55 MYA. These dates are much more recent than previous dates based on molecular-clock methods. In addition, analyses of new sequences from the Atlantic Coastal Forest species A. guariba indicate the presence of two distinct haplogroups corresponding to northern and southern populations with both haplogroups occurring in sympatry within Sao Paulo state. The time of divergence of these two haplogroups is estimated to be 1.2 MYA and so follows quite closely after the divergence of A. guariba and A. belzebul. These more recent dates point to the importance of Pleistocene environmental events as important factors in the diversification of A. belzebul and A. guariba. We discuss the diversification of the three Alouatta species in the context of recent models of climatic change and with regard to recent molecular phylogeographic analyses of other animal groups distributed in Brazil.

  2. Preliminary insight into the age and origin of the Labeobarbus fish species flock from Lake Tana (Ethiopia) using the mtDNA cytochrome b gene.

    PubMed

    de Graaf, Martin; Megens, Hendrik-Jan; Samallo, Johannis; Sibbing, Ferdinand

    2010-02-01

    The high diversity of Cyprinid fish in Ethiopia's Lake Tana appears to be an example of ecological differentiation and assortative mating leading to rapid sympatric speciation. Lake Tana's Labeobarbus species flock consists of 15 morphological and ecological distinct species. This is the first attempt to determine the age and origin and inter-species relationships of Lake Tana's Labeobarbus species using the mtDNA cytochrome b gene. Analysis of cytchrome b sequences shows that Lake Tana's species flock appears to be young but the present dataset did not unequivocally support monophyly of Lake Tana's species. Additional markers are needed to determine whether Lake Tana's labeobarbs originated from a single or multiple incursion(s) of ancestral L. intermedius in the Lake Tana drainage basin, or the disruption of an ancient continuous riverine population by the emergence of the Tissisat waterfalls. Adaptive radiation and speciation within Lake Tana's Labeobarbus species flock may have occurred in the last 10,000-25,000years, following the desiccation of Lake Tana around 17,000years ago, at the same time as Lake Victoria, however, obtaining more data using other (nuclear) markers is urgently required.

  3. Population Structure of mtDNA Variation due to Pleistocene Fluctuations in the South American Maned Wolf (Chrysocyon brachyurus, Illiger, 1815): Management Units for Conservation.

    PubMed

    González, Susana; Cosse, Mariana; Franco, María del Rosario; Emmons, Louise; Vynne, Carly; Duarte, José Maurício Barbanti; Beccacesi, Marcelo D; Maldonado, Jesús E

    2015-01-01

    The maned wolf (Chrysocyon brachyurus) is one of the largest South American canids, and conservation across this charismatic carnivore's large range is presently hampered by a lack of knowledge about possible natural subdivisions which could influence the population's viability. To elucidate the phylogeographic patterns and demographic history of the species, we used 2 mtDNA markers (D-loop and cytochrome b) from 87 individuals collected throughout their range, in Argentina, Bolivia, Brazil, and Uruguay. We found moderate levels of haplotype and nucleotide diversity, and the 14 D-loop haplotypes were closely related. Genetic structure results revealed 4 groups, and when coupled with model inferences from a coalescent analysis, suggested that maned wolves have undergone demographic fluctuations due to changes in climate and habitat during the Pleistocene glaciation period approximately 24000 years before present (YBP). This genetic signature points to an event that occurred within the timing estimated for the start of the contraction of the Cerrado around 50000 YBP. Our results reveal a genetic signature of population size expansion followed by contraction during Pleistocene interglaciations, which had similar impacts on other South American mammals. The 4 groups should for now be considered management units, within which future monitoring efforts should be conducted independently.

  4. Diversity and distribution of white-tailed deer mtdna lineages in chronic wasting disease (cwd) outbreak areas in southern wisconsin, USA

    USGS Publications Warehouse

    Rogers, K.G.; Robinson, S.J.; Samuel, M.D.; Grear, D.A.

    2011-01-01

    Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy affecting North American cervids. Because it is uniformly fatal, the disease is a major concern in the management of white-tailed deer populations. Management programs to control CWD require improved knowledge of deer interaction, movement, and population connectivity that could influence disease transmission and spread. Genetic methods were employed to evaluate connectivity among populations in the CWD management zone of southern Wisconsin. A 576-base-pair region of the mitochondrial DNA of 359 white-tailed deer from 12 sample populations was analyzed. Fifty-eight variable sites were detected within the sequence, defining 43 haplotypes. While most sample populations displayed similar levels of haplotype diversity, individual haplotypes were clustered on the landscape. Spatial clusters of different haplotypes were apparent in distinct ecoregions surrounding CWD outbreak areas. The spatial distribution of mtDNA haplotypes suggests that clustering of the deer matrilineal groups and population connectivity are associated with broad-scale geographic landscape features. These landscape characteristics may also influence the contact rates between groups and therefore the potential spread of CWD; this may be especially true of local disease spread between female social groups. Our results suggest that optimal CWD management needs to be tailored to fit gender-specific dispersal behaviors and regional differences in deer population connectivity. This information will help wildlife managers design surveillance and monitoring efforts based on population interactions and potential deer movement among CWD-affected and unaffected areas. Copyright ?? Taylor & Francis Group, LLC.

  5. Personal identification of cold case remains through combined contribution from anthropological, mtDNA and bomb–pulse dating analyses*†

    PubMed Central

    Speller, Camilla F.; Spalding, Kirsty L.; Buchholz, Bruce A.; Hildebrand, Dean; Moore, Jason; Mathewes, Rolf; Skinner, Mark F.; Yang, Dongya Y.

    2013-01-01

    In 1968, a child’s cranium was recovered from the banks of a northern Canadian river, and held in trust until the ‘cold case’ was re-opened in 2005. The cranium underwent re-analysis at the Centre for Forensic Research, Simon Fraser University, using recently developed anthropological, ‘bomb-pulse’ radiocarbon analysis and forensic DNA techniques. Craniometrics, skeletal ossification and dental formation indicated an age-at-death of 4.4 ±1 years. Radiocarbon analysis of enamel from two teeth indicated a year of birth between 1958–1962. Forensic DNA analysis indicated the child was male, and the obtained mitochondrial profile matched a living maternal relative of the presumed missing child. These multi-disciplinary analyses resulted in a legal identification 41 years after the discovery of the remains, highlighting the enormous potential of combining radiocarbon analysis with anthropological and mtDNA analyses in producing confident personal identifications for forensic cold cases dating to within the last 60 years. PMID:22804335

  6. One species or several? Discordant patterns of geographic variation between allozymes and mtDNA sequences among spiders in the genus Metepeira (Araneae: Araneidae).

    PubMed

    Piel, W H; Nutt, K J

    2000-06-01

    Paradoxically, an allozyme study of Metepeira "spinipes" (sensu lato) demonstrated extensive gene flow among four populations whose members are nevertheless morphologically and behaviorally distinct. Initially, the authors tentatively concluded that the populations exhibited panmixis and suggested that local environmental effects accounted for the apparent morphological and behavioral differences. However, they later concluded that such differences were too great to be accounted for by the environment alone and that the four populations actually represented three different species. To confirm that the allozyme results were, in fact, artifactual, we reexamined the relationships among these populations by sequencing a portion of the 12S mtDNA ribosomal subunit. In contrast to the allozyme result, our results demonstrate good agreement between patterns of genetic and morphological/behavioral variation. We suggest (1) that the allozyme allele frequencies are homogenized by balancing selection, not gene flow as was previously concluded, and therefore (2) that this study provides another instance in which inferences about population structures from allozyme data are misleading.

  7. Phylogenetic analysis of the endangered takin in the confluent zone of the Qinling and Minshan Mountains using mtDNA control region.

    PubMed

    Yao, Gang; Li, Yanhong; Li, Dayong; Williams, Peter; Hu, Jie

    2016-07-01

    The takin (Budorcas taxicolor) is an Endangered ungulate. We analyzed the variation within mtDNA control region sequences of takin populations in the Qinling Mountains, the Minshan Mountains and the confluence of these two mountain ranges. We did not find any shared haplotypes among the populations. We observed apparent variation in the control region length among the three populations, and independent population expansions in the late of Pleistocene, which suggests these populations may have independent evolutionary histories. We found only one haplotype, and the lowest measures of genetic diversity (h = 0; π = 0) in the population from the confluent zone, which suggests populations in the confluent zone may have grown from small founder populations and gene flow with other populations has ceased. Based on their phylogenetic relationships, we concluded that the takin population in the confluent zone was in the same clade as the Tangjiahe population, which suggests that these takin populations are Sichuan takin (Budorcas taxicolor tibetana).

  8. Persistent heteroplasmy of a mutation in the human mtDNA control region: hypermutation as an apparent consequence of simple-repeat expansion/contraction.

    PubMed Central

    Howell, N; Smejkal, C B

    2000-01-01

    In the genealogical and phylogenetic analyses that are reported here, we obtained evidence for an unusual pattern of mutation/reversion in the human mitochondrial genome. The cumulative results indicate that, when there is a T-->C polymorphism at nt 16189 and a C-->T substitution at nt 16192, there is an extremely high rate of reversion (hypermutation) at the latter site. The apparent reversion rate is sufficiently high that there is persistent heteroplasmy at nt 16192 in maternal lineages and at the phylogenetic level, a situation that is similar to that observed for the rapid expansion/contraction of simple repeats within the control region. This is the first specific instance in which the mutation frequency at one site in the D-loop is markedly influenced by the local sequence "context." The 16189 T-->C polymorphism lengthens a (C:G)n simple repeat, which then undergoes expansion and contraction, probably through replication slippage. This proclivity toward expansion/contraction is more pronounced when there is a C residue, rather than a T, at nt 16192. The high T-->C reversion frequency at nt 16192 apparently is the result of polymerase misincorporation or slippage during replication, the same mechanism that also causes the expansion/contraction of this simple-repeat sequence. In addition to the first analysis of this mitochondrial hypermutation process, these results also yield mechanistic insights into the expansion/contraction of simple-repeat sequences in mtDNA. PMID:10762545

  9. Diversity and distribution of white-tailed deer mtDNA lineages in chronic wasting disease (CWD) outbreak areas in southern Wisconsin, USA.

    PubMed

    Rogers, Kip G; Robinson, Stacie J; Samuel, Michael D; Grear, Daniel A

    2011-01-01

    Chronic wasting disease (CWD) is a transmissible spongiform encephalopathy affecting North American cervids. Because it is uniformly fatal, the disease is a major concern in the management of white-tailed deer populations. Management programs to control CWD require improved knowledge of deer interaction, movement, and population connectivity that could influence disease transmission and spread. Genetic methods were employed to evaluate connectivity among populations in the CWD management zone of southern Wisconsin. A 576-base-pair region of the mitochondrial DNA of 359 white-tailed deer from 12 sample populations was analyzed. Fifty-eight variable sites were detected within the sequence, defining 43 haplotypes. While most sample populations displayed similar levels of haplotype diversity, individual haplotypes were clustered on the landscape. Spatial clusters of different haplotypes were apparent in distinct ecoregions surrounding CWD outbreak areas. The spatial distribution of mtDNA haplotypes suggests that clustering of the deer matrilineal groups and population connectivity are associated with broad-scale geographic landscape features. These landscape characteristics may also influence the contact rates between groups and therefore the potential spread of CWD; this may be especially true of local disease spread between female social groups. Our results suggest that optimal CWD management needs to be tailored to fit gender-specific dispersal behaviors and regional differences in deer population connectivity. This information will help wildlife managers design surveillance and monitoring efforts based on population interactions and potential deer movement among CWD-affected and unaffected areas.

  10. Mitogenomic analysis of a 50-generation chicken pedigree reveals a rapid rate of mitochondrial evolution and evidence for paternal mtDNA inheritance.

    PubMed

    Alexander, Michelle; Ho, Simon Y W; Molak, Martyna; Barnett, Ross; Carlborg, Örjan; Dorshorst, Ben; Honaker, Christa; Besnier, Francois; Wahlberg, Per; Dobney, Keith; Siegel, Paul; Andersson, Leif; Larson, Greger

    2015-10-01

    Mitochondrial genomes represent a valuable source of data for evolutionary research, but studies of their short-term evolution have typically been limited to invertebrates, humans and laboratory organisms. Here we present a detailed study of 12 mitochondrial genomes that span a total of 385 transmissions in a well-documented 50-generation pedigree in which two lineages of chickens were selected for low and high juvenile body weight. These data allowed us to test the hypothesis of time-dependent evolutionary rates and the assumption of strict maternal mitochondrial transmission, and to investigate the role of mitochondrial mutations in determining phenotype. The identification of a non-synonymous mutation in ND4L and a synonymous mutation in CYTB, both novel mutations in Gallus, allowed us to estimate a molecular rate of 3.13 × 10(-7) mutations/site/year (95% confidence interval 3.75 × 10(-8)-1.12 × 10(-6)). This is substantially higher than avian rate estimates based upon fossil calibrations. Ascertaining which of the two novel mutations was present in an additional 49 individuals also revealed an instance of paternal inheritance of mtDNA. Lastly, an association analysis demonstrated that neither of the point mutations was strongly associated with the phenotypic differences between the two selection lines. Together, these observations reveal the highly dynamic nature of mitochondrial evolution over short time periods.

  11. Post-glacial recolonization of the Great Lakes region by the common gartersnake (Thamnophis sirtalis) inferred from mtDNA sequences.

    PubMed

    Placyk, John S; Burghardt, Gordon M; Small, Randall L; King, Richard B; Casper, Gary S; Robinson, Jace W

    2007-05-01

    Pleistocene events played an important role in the differentiation of North American vertebrate populations. Michigan, in particular, and the Great Lakes region, in general, were greatly influenced by the last glaciation. While several hypotheses regarding the recolonization of this region have been advanced, none have been strongly supported. We generated 148 complete ND2 mitochondrial DNA (mtDNA) sequences from common gartersnake (Thamnophis sirtalis) populations throughout the Great Lakes region to evaluate phylogeographic patterns and population structure and to determine whether the distribution of haplotypic variants is related to the post-Pleistocene retreat of the Wisconsinan glacier. The common gartersnake was utilized, as it is believed to have been one of the primary vertebrate invaders of the Great Lakes region following the most recent period of glacial retreat and because it has been a model species for a variety of evolutionary, ecological, behavioral, and physiological studies. Several genetically distinct evolutionary lineages were supported by both genealogical and molecular population genetic analyses, although to different degrees. The geographic distribution of the majority of these lineages is interpreted as reflecting post-glacial recolonization dynamics during the late Pleistocene. These findings generally support previous hypotheses of range expansion in this region.

  12. Microsatellite and mtDNA analysis of lake trout, Salvelinus namaycush, from Great Bear Lake, Northwest Territories: impacts of historical and contemporary evolutionary forces on Arctic ecosystems

    PubMed Central

    Harris, Les N; Howland, Kimberly L; Kowalchuk, Matthew W; Bajno, Robert; Lindsay, Melissa M; Taylor, Eric B

    2013-01-01

    Resolving the genetic population structure of species inhabiting pristine, high latitude ecosystems can provide novel insights into the post-glacial, evolutionary processes shaping the distribution of contemporary genetic variation. In this study, we assayed genetic variation in lake trout (Salvelinus namaycush) from Great Bear Lake (GBL), NT and one population outside of this lake (Sandy Lake, NT) at 11 microsatellite loci and the mtDNA control region (d-loop). Overall, population subdivision was low, but significant (global FST θ = 0.025), and pairwise comparisons indicated that significance was heavily influenced by comparisons between GBL localities and Sandy Lake. Our data indicate that there is no obvious genetic structure among the various basins within GBL (global FST = 0.002) despite the large geographic distances between sampling areas. We found evidence of low levels of contemporary gene flow among arms within GBL, but not between Sandy Lake and GBL. Coalescent analyses suggested that some historical gene flow occurred among arms within GBL and between GBL and Sandy Lake. It appears, therefore, that contemporary (ongoing dispersal and gene flow) and historical (historical gene flow and large founding and present-day effective population sizes) factors contribute to the lack of neutral genetic structure in GBL. Overall, our results illustrate the importance of history (e.g., post-glacial colonization) and contemporary dispersal ecology in shaping genetic population structure of Arctic faunas and provide a better understanding of the evolutionary ecology of long-lived salmonids in pristine, interconnected habitats. PMID:23404390

  13. Green turtles (Chelonia mydas) foraging at Arvoredo Island in Southern Brazil: Genetic characterization and mixed stock analysis through mtDNA control region haplotypes.

    PubMed

    Proietti, Maíra Carneiro; Lara-Ruiz, Paula; Reisser, Júlia Wiener; da Silva Pinto, Luciano; Dellagostin, Odir Antonio; Marins, Luis Fernando

    2009-07-01

    We analyzed mtDNA control region sequences of green turtles (Chelonia mydas) from Arvoredo Island, a foraging ground in southern Brazil, and identified eight haplotypes. Of these, CM-A8 (64%) and CM-A5 (22%) were dominant, the remainder presenting low frequencies (< 5%). Haplotype (h) and nucleotide (π) diversities were 0.5570 ± 0.0697 and 0.0021 ± 0.0016, respectively. Exact tests of differentiation and AMOVA Φ(ST) pairwise values between the study area and eight other Atlantic foraging grounds revealed significant differences in most areas, except Ubatuba and Rocas/Noronha, in Brazil (p > 0.05). Mixed Stock Analysis, incorporating eleven Atlantic and one Mediterranean rookery as possible sources of individuals, indicated Ascension and Aves islands as the main contributing stocks to the Arvoredo aggregation (68.01% and 22.96%, respectively). These results demonstrate the extensive relationships between Arvoredo Island and other Atlantic foraging and breeding areas. Such an understanding provides a framework for establishing adequate management and conservation strategies for this endangered species.

  14. Microsatellite and mtDNA analysis of lake trout, Salvelinus namaycush, from Great Bear Lake, Northwest Territories: impacts of historical and contemporary evolutionary forces on Arctic ecosystems.

    PubMed

    Harris, Les N; Howland, Kimberly L; Kowalchuk, Matthew W; Bajno, Robert; Lindsay, Melissa M; Taylor, Eric B

    2012-01-01

    Resolving the genetic population structure of species inhabiting pristine, high latitude ecosystems can provide novel insights into the post-glacial, evolutionary processes shaping the distribution of contemporary genetic variation. In this study, we assayed genetic variation in lake trout (Salvelinus namaycush) from Great Bear Lake (GBL), NT and one population outside of this lake (Sandy Lake, NT) at 11 microsatellite loci and the mtDNA control region (d-loop). Overall, population subdivision was low, but significant (global F(ST) θ = 0.025), and pairwise comparisons indicated that significance was heavily influenced by comparisons between GBL localities and Sandy Lake. Our data indicate that there is no obvious genetic structure among the various basins within GBL (global F(ST) = 0.002) despite the large geographic distances between sampling areas. We found evidence of low levels of contemporary gene flow among arms within GBL, but not between Sandy Lake and GBL. Coalescent analyses suggested that some historical gene flow occurred among arms within GBL and between GBL and Sandy Lake. It appears, therefore, that contemporary (ongoing dispersal and gene flow) and historical (historical gene flow and large founding and present-day effective population sizes) factors contribute to the lack of neutral genetic structure in GBL. Overall, our results illustrate the importance of history (e.g., post-glacial colonization) and contemporary dispersal ecology in shaping genetic population structure of Arctic faunas and provide a better understanding of the evolutionary ecology of long-lived salmonids in pristine, interconnected habitats.

  15. Integrating Art.

    ERIC Educational Resources Information Center

    BCATA Journal for Art Teachers, 1991

    1991-01-01

    These articles focus on art as a component of interdisciplinary integration. (1) "Integrated Curriculum and the Visual Arts" (Anna Kindler) considers various aspects of integration and implications for art education. (2) "Integration: The New Literacy" (Tim Varro) illustrates how the use of technology can facilitate…

  16. The A1555G mutation in the 12S rRNA gene of human mtDNA: recurrent origins and founder events in families affected by sensorineural deafness.

    PubMed

    Torroni, A; Cruciani, F; Rengo, C; Sellitto, D; López-Bigas, N; Rabionet, R; Govea, N; López De Munain, A; Sarduy, M; Romero, L; Villamar, M; del Castillo, I; Moreno, F; Estivill, X; Scozzari, R

    1999-11-01

    The mtDNA variation of 50 Spanish and 4 Cuban families affected by nonsyndromic sensorineural deafness due to the A1555G mutation in the 12S rRNA gene was studied by high-resolution RFLP analysis and sequencing of the control region. Phylogenetic analyses of haplotypes and detailed survey of population controls revealed that the A1555G mutation can be attributed to >/=30 independent mutational events among the 50 Spanish families and that it occurs on mtDNA haplogroups that are common in all European populations. This indicates that the relatively high detection rate of this mutation in Spain is not due to sampling biases or to a single major founder event. Moreover, the distribution of these mutational events on different haplogroups is compatible with a random occurrence of the A1555G mutation and tends to support the conclusion that mtDNA backgrounds do not play a significant role in the expression of the mutation. Overall, these findings appear to indicate that the rare detection of this mutation in other populations is most likely due to inadequacy in patient ascertainment and molecular screening. This probable lack of identification of the A1555G mutation in subjects affected by sensorineural hearing loss implies that their maternally related relatives are not benefiting from presymptomatic detection and information concerning their increased risk of ototoxicity due to aminoglycoside treatments.

  17. The A1555G Mutation in the 12S rRNA Gene of Human mtDNA: Recurrent Origins and Founder Events in Families Affected by Sensorineural Deafness

    PubMed Central

    Torroni, Antonio; Cruciani, Fulvio; Rengo, Chiara; Sellitto, Daniele; López-Bigas, Núria; Rabionet, Raquel; Govea, Nancy; López de Munain, Adolfo; Sarduy, Maritza; Romero, Lourdes; Villamar, Manuela; del Castillo, Ignacio; Moreno, Felipe; Estivill, Xavier; Scozzari, Rosaria

    1999-01-01

    Summary The mtDNA variation of 50 Spanish and 4 Cuban families affected by nonsyndromic sensorineural deafness due to the A1555G mutation in the 12S rRNA gene was studied by high-resolution RFLP analysis and sequencing of the control region. Phylogenetic analyses of haplotypes and detailed survey of population controls revealed that the A1555G mutation can be attributed to ⩾30 independent mutational events among the 50 Spanish families and that it occurs on mtDNA haplogroups that are common in all European populations. This indicates that the relatively high detection rate of this mutation in Spain is not due to sampling biases or to a single major founder event. Moreover, the distribution of these mutational events on different haplogroups is compatible with a random occurrence of the A1555G mutation and tends to support the conclusion that mtDNA backgrounds do not play a significant role in the expression of the mutation. Overall, these findings appear to indicate that the rare detection of this mutation in other populations is most likely due to inadequacy in patient ascertainment and molecular screening. This probable lack of identification of the A1555G mutation in subjects affected by sensorineural hearing loss implies that their maternally related relatives are not benefiting from presymptomatic detection and information concerning their increased risk of ototoxicity due to aminoglycoside treatments. PMID:10521300

  18. Newly identified protein Imi1 affects mitochondrial integrity and glutathione homeostasis in Saccharomyces cerevisiae.

    PubMed

    Kowalec, Piotr; Grynberg, Marcin; Pająk, Beata; Socha, Anna; Winiarska, Katarzyna; Fronk, Jan; Kurlandzka, Anna

    2015-09-01

    Glutathione homeostasis is crucial for cell functioning. We describe a novel Imi1 protein of Saccharomyces cerevisiae affecting mitochondrial integrity and involved in controlling glutathione level. Imi1 is cytoplasmic and, except for its N-terminal Flo11 domain, has a distinct solenoid structure. A lack of Imi1 leads to mitochondrial lesions comprising aberrant morphology of cristae and multifarious mtDNA rearrangements and impaired respiration. The mitochondrial malfunctioning is coupled to significantly decrease the level of intracellular reduced glutathione without affecting oxidized glutathione, which decreases the reduced/oxidized glutathione ratio. These defects are accompanied by decreased cadmium sensitivity and increased phytochelatin-2 level.

  19. Incongruence between mtDNA and nuclear data in the freshwater mussel genus Cyprogenia (Bivalvia: Unionidae) and its impact on species delineation.

    PubMed

    Chong, Jer Pin; Harris, John L; Roe, Kevin J

    2016-04-01

    Accurately identifying species is a crucial step for developing conservation strategies for freshwater mussels, one of the most imperiled faunas in North America. This study uses genetic data to re-examine species delineation in the genus Cyprogenia. Historically, Cyprogenia found west of the Mississippi River have been ascribed to Cyprogenia aberti (Conrad 1850), and those east of the Mississippi River were classified as Cyprogenia stegaria (Rafinesque 1820). Previous studies using mitochondrial DNA sequences indicated that C. aberti and C. stegaria were not reciprocally monophyletic groups, suggesting the need for systematic revision. We generated a novel dataset consisting of 10 microsatellite loci and combined it with sequence data from the mitochondrial ND1 gene for 223 Cyprogenia specimens. Bayesian analysis of the ND1 nucleotide sequences identified two divergent clades that differ by 15.9%. Members of these two clades occur sympatrically across most sampling locations. In contrast, microsatellite genotypes support recognition of three allopatric clusters defined by major hydrologic basins. The divergent mitochondrial lineages are highly correlated with the color of the conglutinate lures used by mussels to attract and infest host fishes, and tests for selection at the ND1 locus were positive. We infer that the incongruence between mtDNA and microsatellite data in Cyprogenia may be the result of a combination of incomplete lineage sorting and balancing selection on lure color. Our results provide further evidence that mitochondrial markers are not always neutral with respect to selection, and highlight the potential problems of relying on a single-locus-marker for delineating species.

  20. Neither philopatric nor panmictic: microsatellite and mtDNA evidence suggests lack of natal homing but limits to dispersal in Pacific lamprey.

    PubMed

    Spice, Erin K; Goodman, Damon H; Reid, Stewart B; Docker, Margaret F

    2012-06-01

    Most species with lengthy migrations display some degree of natal homing; some (e.g. migratory birds and anadromous salmonids) show spectacular feats of homing. However, studies of the sea lamprey (Petromyzon marinus) indicate that this anadromous species locates spawning habitat based on pheromonal cues from larvae rather than through philopatry. Previous genetic studies in the anadromous Pacific lamprey (Entosphenus tridentatus) have both supported and rejected the hypothesis of natal homing. To resolve this, we used nine microsatellite loci to examine the population structure in 965 Pacific lamprey from 20 locations from central British Columbia to southern California and supplemented this analysis with mitochondrial DNA restriction fragment length polymorphism analysis on a subset of 530 lamprey. Microsatellite analysis revealed (i) relatively low but often statistically significant genetic differentiation among locations (97% pairwise F(ST) values were <0.04 but 73.7% were significant); and (ii) weak but significant isolation by distance (r(2) = 0.0565, P = 0.0450) but no geographic clustering of samples. The few moderate F(ST) values involved comparisons with sites that were geographically distant or far upstream. The mtDNA analysis--although providing less resolution among sites (only 4.7%F(ST) values were significant)--was broadly consistent with the microsatellite results: (i) the southernmost site and some sites tributary to the Salish Sea were genetically distinct; and (ii) southern sites showed higher haplotype and private haplotype richness. These results are inconsistent with philopatry, suggesting that anadromous lampreys are unusual among species with long migrations, but suggest that limited dispersal at sea precludes panmixia in this species.

  1. Genetic diversity and phylogeography of highly zoonotic Echinococcus granulosus genotype G1 in the Americas (Argentina, Brazil, Chile and Mexico) based on 8279bp of mtDNA.

    PubMed

    Laurimäe, Teivi; Kinkar, Liina; Andresiuk, Vanessa; Haag, Karen Luisa; Ponce-Gordo, Francisco; Acosta-Jamett, Gerardo; Garate, Teresa; Gonzàlez, Luis Miguel; Saarma, Urmas

    2016-11-01

    Echinococcus granulosus is a taeniid cestode and the etiological agent of an infectious zoonotic disease known as cystic echinococcosis (CE) or hydatid disease. CE is a serious public health concern in many parts of the world, including the Americas, where it is highly endemic in many regions. Echinococcus granulosus displays high intraspecific genetic variability and is divided into multiple genotypes (G1-G8, G10) with differences in their biology and etiology. Of these, genotype G1 is responsible for the majority of human and livestock infections and has the broadest host spectrum. However, despite the high significance to the public and livestock health, the data on genetic variability and regional genetic differences of genotype G1 in America are scarce. The aim of this study was to evaluate the genetic variability and phylogeography of G1 in several countries in America by sequencing a large portion of the mitochondrial genome. We analysed 8279bp of mtDNA for 52 E. granulosus G1 samples from sheep, cattle and pigs collected in Argentina, Brazil, Chile and Mexico, covering majority of countries in the Americas where G1 has been reported. The phylogenetic network revealed 29 haplotypes and a high haplotype diversity (Hd=0.903). The absence of phylogeographic segregation between different regions in America suggests the importance of animal transportation in shaping the genetic structure of E. granulosus G1. In addition, our study revealed many highly divergent haplotypes, indicating a long and complex evolutionary history of E. granulosus G1 in the Americas.

  2. West Eurasian mtDNA lineages in India: an insight into the spread of the Dravidian language and the origins of the caste system.

    PubMed

    Palanichamy, Malliya Gounder; Mitra, Bikash; Zhang, Cai-Ling; Debnath, Monojit; Li, Gui-Mei; Wang, Hua-Wei; Agrawal, Suraksha; Chaudhuri, Tapas Kumar; Zhang, Ya-Ping

    2015-06-01

    There is no indication from the previous mtDNA studies that west Eurasian-specific subclades have evolved within India and played a role in the spread of languages and the origins of the caste system. To address these issues, we have screened 14,198 individuals (4208 from this study) and analyzed 112 mitogenomes (41 new sequences) to trace west Eurasian maternal ancestry. This has led to the identification of two autochthonous subhaplogroups--HV14a1 and U1a1a4, which are likely to have originated in the Dravidian-speaking populations approximately 10.5-17.9 thousand years ago (kya). The carriers of these maternal lineages might have settled in South India during the time of the spread of the Dravidian language. In addition to this, we have identified several subsets of autochthonous U7 lineages, including U7a1, U7a2b, U7a3, U7a6, U7a7, and U7c, which seem to have originated particularly in the higher-ranked caste populations in relatively recent times (2.6-8.0 kya with an average of 5.7 kya). These lineages have provided crucial clues to the differentiation of the caste system that has occurred during the recent past and possibly, this might have been influenced by the Indo-Aryan migration. The remaining west Eurasian lineages observed in the higher-ranked caste groups, like the Brahmins, were found to cluster with populations who possibly arrived from west Asia during more recent times.

  3. New polymorphic mtDNA restriction site in the 12S rRNA gene detected in Tunisian patients with non-syndromic hearing loss

    SciTech Connect

    Mkaouar-Rebai, Emna Tlili, Abdelaziz; Masmoudi, Saber; Charfeddine, Ilhem; Fakhfakh, Faiza

    2008-05-09

    The 12S rRNA gene was shown to be a hot spot for aminoglycoside-induced and non-syndromic hearing loss since several deafness-associated mtDNA mutations were identified in this gene. Among them, we distinguished the A1555G, the C1494T and the T1095C mutations and C-insertion or deletion at position 961. One hundred Tunisian patients with non-syndromic hearing loss and 100 hearing individuals were analysed in this study. A PCR-RFLP analysis with HaeIII restriction enzyme showed the presence of the A1555G mutation in the 12S rRNA gene in only one out of the 100 patients. In addition, PCR-RFLP and radioactive PCR revealed the presence of a new HaeIII polymorphic restriction site in the same gene of 12S rRNA site in 4 patients with non-syndromic hearing loss. UVIDOC-008-XD analyses showed the presence of this new polymorphic restriction site with a variable heteroplasmic rates at position +1517 of the human mitochondrial genome. On the other hand, direct sequencing of the entire mitochondrial 12S rRNA gene in the 100 patients and in 100 hearing individuals revealed the presence of the A750G and A1438G polymorphisms and the absence of the C1494T, T1095C and 961insC mutations in all the tested individuals. Sequencing of the whole mitochondrial genome in the 4 patients showing the new HaeIII polymorphic restriction site revealed only the presence of the A8860G transition in the MT-ATP6 gene and the A4769G polymorphism in the ND2 gene.

  4. mtDNA data indicate a single origin for dogs south of Yangtze River, less than 16,300 years ago, from numerous wolves.

    PubMed

    Pang, Jun-Feng; Kluetsch, Cornelya; Zou, Xiao-Ju; Zhang, Ai-bing; Luo, Li-Yang; Angleby, Helen; Ardalan, Arman; Ekström, Camilla; Sköllermo, Anna; Lundeberg, Joakim; Matsumura, Shuichi; Leitner, Thomas; Zhang, Ya-Ping; Savolainen, Peter

    2009-12-01

    There is no generally accepted picture of where, when, and how the domestic dog originated. Previous studies of mitochondrial DNA (mtDNA) have failed to establish the time and precise place of origin because of lack of phylogenetic resolution in the so far studied control region (CR), and inadequate sampling. We therefore analyzed entire mitochondrial genomes for 169 dogs to obtain maximal phylogenetic resolution and the CR for 1,543 dogs across the Old World for a comprehensive picture of geographical diversity. Hereby, a detailed picture of the origins of the dog can for the first time be suggested. We obtained evidence that the dog has a single origin in time and space and an estimation of the time of origin, number of founders, and approximate region, which also gives potential clues about the human culture involved. The analyses showed that dogs universally share a common homogenous gene pool containing 10 major haplogroups. However, the full range of genetic diversity, all 10 haplogroups, was found only in southeastern Asia south of Yangtze River, and diversity decreased following a gradient across Eurasia, through seven haplogroups in Central China and five in North China and Southwest (SW)Asia, down to only four haplogroups in Europe. The mean sequence distance to ancestral haplotypes indicates an origin 5,400-16,300 years ago (ya) from at least 51 female wolf founders. These results indicate that the domestic dog originated in southern China less than 16,300 ya, from several hundred wolves. The place and time coincide approximately with the origin of rice agriculture, suggesting that the dogs may have originated among sedentary hunter-gatherers or early farmers, and the numerous founders indicate that wolf taming was an important culture trait.

  5. Molecular evolution in space and through time: mtDNA phylogeography of the Olive Sunbird (Nectarinia olivacea/obscura) throughout continental Africa.

    PubMed

    Bowie, Rauri C K; Fjeldså, Jon; Hackett, Shannon J; Crowe, Timothy M

    2004-10-01

    This study constitutes the first investigation of the phylogeographic structure of a forest bird distributed throughout the montane and lowland forest biomes of Africa. The key objective was to investigate the importance of Pleistocene climatic cycles on avian diversification across Africa. The Olive Sunbird is a relatively large polytypic sunbird widely distributed throughout evergreen, montane and coastal forests in Africa. Recently, it was split into two species, the Eastern Olive Sunbird (Nectarinia olivacea) and the Western Olive Sunbird (Nectarinia obscura), based on morphological grounds. Analyses of a 395bp fragment of the mtDNA NADH subunit 3 gene with flanking tRNA sequences, from 196 individuals of N. olivacea and 86 from N. obscura indicate that genetic divergence levels are low (1.0-2.4%) across some 9000km, from Ghana in the northwest of Africa to KwaZulu-Natal in eastern South Africa. Neither currently recognized Olive Sunbird species were monophyletic using either parsimony or likelihood tree-building methods. Phi(ST) values suggested that there was less variation partitioned among species than between most neighboring regions. Genetic diversity within the N. olivacea/obscura complex was dominated by three star-like phylogenies linked to each other by a single mutational step and two subnetworks (IV and V) separated from the core star-like phylogenies (subnetworks I, II, and III) by five to six mutational steps. The dominant evolutionary mechanism shaping genetic variation within the N. olivacea/obscura complex as identified by nested-clade analyses, appears to be one of range expansion possibly out of East Africa associated with a period of forest expansion during the mid-Pleistocene, some 1.1-0.7 million years ago. Mismatch profiles suggested that secondary contact has occurred between eastern and western lineages within the Ufipa Escarpment and possibly Zimbabwe, as well as between eastern lineages in the Kenyan Highlands and northern Eastern Arc

  6. Re-examination of population structure and phylogeography of hawksbill turtles in the wider Caribbean using longer mtDNA sequences.

    PubMed

    Leroux, Robin A; Dutton, Peter H; Abreu-Grobois, F Alberto; Lagueux, Cynthia J; Campbell, Cathi L; Delcroix, Eric; Chevalier, Johan; Horrocks, Julia A; Hillis-Starr, Zandy; Troëng, Sebastian; Harrison, Emma; Stapleton, Seth

    2012-01-01

    Management of the critically endangered hawksbill turtle in the Wider Caribbean (WC) has been hampered by knowledge gaps regarding stock structure. We carried out a comprehensive stock structure re-assessment of 11 WC hawksbill rookeries using longer mtDNA sequences, larger sample sizes (N = 647), and additional rookeries compared to previous surveys. Additional variation detected by 740 bp sequences between populations allowed us to differentiate populations such as Barbados-Windward and Guadeloupe (F (st) = 0.683, P < 0.05) that appeared genetically indistinguishable based on shorter 380 bp sequences. POWSIM analysis showed that longer sequences improved power to detect population structure and that when N < 30, increasing the variation detected was as effective in increasing power as increasing sample size. Geographic patterns of genetic variation suggest a model of periodic long-distance colonization coupled with region-wide dispersal and subsequent secondary contact within the WC. Mismatch analysis results for individual clades suggest a general population expansion in the WC following a historic bottleneck about 100 000-300 000 years ago. We estimated an effective female population size (N (ef)) of 6000-9000 for the WC, similar to the current estimated numbers of breeding females, highlighting the importance of these regional rookeries to maintaining genetic diversity in hawksbills. Our results provide a basis for standardizing future work to 740 bp sequence reads and establish a more complete baseline for determining stock boundaries in this migratory marine species. Finally, our findings illustrate the value of maintaining an archive of specimens for re-analysis as new markers become available.

  7. Single Nucleotides in the mtDNA Sequence Modify Mitochondrial Molecular Function and Are Associated with Sex-Specific Effects on Fertility and Aging.

    PubMed

    Camus, M Florencia; Wolf, Jochen B W; Morrow, Edward H; Dowling, Damian K

    2015-10-19

    Mitochondria underpin energy conversion in eukaryotes. Their small genomes have been the subject of increasing attention, and there is evidence that mitochondrial genetic variation can affect evolutionary trajectories and shape the expression of life-history traits considered to be key human health indicators [1, 2]. However, it is not understood how genetic variation across a diminutive genome, which in most species harbors only about a dozen protein-coding genes, can exert broad-scale effects on the organismal phenotype [2, 3]. Such effects are particularly puzzling given that the mitochondrial genes involved are under strong evolutionary constraint and that mitochondrial gene expression is highly conserved across diverse taxa [4]. We used replicated genetic lines in the fruit fly, Drosophila melanogaster, each characterized by a distinct and naturally occurring mitochondrial haplotype placed alongside an isogenic nuclear background. We demonstrate that sequence variation within the mitochondrial DNA (mtDNA) affects both the copy number of mitochondrial genomes and patterns of gene expression across key mitochondrial protein-coding genes. In several cases, haplotype-mediated patterns of gene expression were gene-specific, even for genes from within the same transcriptional units. This invokes post-transcriptional processing of RNA in the regulation of mitochondrial genetic effects on organismal phenotypes. Notably, the haplotype-mediated effects on gene expression could be traced backward to the level of individual nucleotides and forward to sex-specific effects on fertility and longevity. Our study thus elucidates how small-scale sequence changes in the mitochondrial genome can achieve broad-scale regulation of health-related phenotypes and even contribute to sex-related differences in longevity.

  8. Integration, Resegregation and Integration Maintenance.

    ERIC Educational Resources Information Center

    Peterman, William A.

    Recent increases in black migration to the suburbs and the continuing existence of discrimination in housing have emphasized the issues of integration and resegregation in suburban municipalities. To prevent resegregation, many integrated municipalities have adopted integration maintenance measures such as efforts to inform people that racial…

  9. Comparative mtDNA phylogeography of neotropical freshwater fishes: testing shared history to infer the evolutionary landscape of lower Central America.

    PubMed

    Bermingham, E; Martin, A P

    1998-04-01

    Historical biogeography seeks to explain contemporary distributions of taxa in the context of intrinsic biological and extrinsic geological and climatic factors. To decipher the relative importance of biological characteristics vs. environmental conditions, it is necessary to ask whether groups of taxa with similar distributions share the same history of diversification. Because all of the taxa will have shared the same climatic and geological history, evidence of shared history across multiple species provides an estimate of the role of extrinsic factors in shaping contemporary biogeographic patterns. Similarly, differences in the records of evolutionary history across species will probably be signatures of biological differences. In this study, we focus on inferring the evolutionary history for geographical populations and closely related species representing three genera of primary freshwater fishes that are widely distributed in lower Central America (LCA) and northwestern Colombia. Analysis of mitochondrial gene trees provides the opportunity for robust tests of shared history across taxa. Moreover, because mtDNA permits inference of the temporal scale of diversification we can test hypotheses regarding the chronological development of the Isthmian corridor linking North and South America. We have focused attention on two issues. First, we show that many of the distinct populations of LCA fishes diverged in a relatively brief period of time thus limiting the phylogenetic signal available for tests of shared history. Second, our results provide reduced evidence of shared history when all drainages are included in the analysis because of inferred dispersion events that obscure the evolutionary history among drainage basins. When we restrict the analysis to areas that harbour endemic mitochondrial lineages, there is evidence of shared history across taxa. We hypothesize that there were two to three distinct waves of invasion into LCA from putative source

  10. The mtDNA nt7778 G/T polymorphism augments formation of lymphocytic foci but does not aggravate cerulein-induced acute pancreatitis in mice.

    PubMed

    Müller, Sarah; Krüger, Burkhard; Lange, Falko; Bock, Cristin N; Nizze, Horst; Glass, Änne; Ibrahim, Saleh M; Jaster, Robert

    2014-01-01

    A polymorphism in the ATP synthase 8 (ATP8) gene of the murine mitochondrial genome, G-to-T transversion at position 7778, has been suggested to increase susceptibility to multiple autoimmune diseases, including autoimmune pancreatitis (AIP). The polymorphism also induces mitochondrial reactive oxygen species generation, secretory dysfunction and β-cell mass adaptation. Here, we have used two conplastic mouse strains, C57BL/6N-mtAKR/J (B6-mtAKR; nt7778 G; control) and C57BL/6N-mtFVB/N (B6-mtFVB; nt7778 T), to address the question if the polymorphism also affects the course of cerulein-induced acute pancreatitis in mice. Therefore, two age groups of mice (3 and 12-month-old, respectively) were subjected to up to 7 injections of the secretagogue cerulein (50 µg/kg body weight) at hourly intervals. Disease severity was assessed at time points from 3 hours to 7 days based on pancreatic histopathology, serum levels of α-amylase and activities of myeloperoxidase (MPO) in lung tissue. A comparison of cerulein-induced pancreatic tissue damage and increases of α-amylase and MPO activities showed no differences between the age-matched groups of both strains. Interestingly, histological evaluation of pancreatic tissue of both untreated and cerulein-treated B6-mtAKR and B6-mtFVB mice also revealed the presence of infiltrates of immune cells surrounding ducts and vessels; a finding that is compatible with an early stage of AIP. After recovery from cerulein-induced pancreatitis (day 7 after the injections), 12-month-old B6-mtFVB mice but not B6-mtAKR mice displayed aggravated lymphocytic lesions. A comparison of 12-month-old mice with other age groups of both strains revealed that lymphocytic foci were largely absent in 3-month-old mice, while 24-month-old mice were more affected. Together, our data suggest that the mtDNA nt7778 G/T polymorphism does not aggravate cerulein-induced acute pancreatitis. Autoimmune-like lesions, however, may progress faster if additional tissue

  11. Phylogeography of the common vampire bat (Desmodus rotundus): Marked population structure, Neotropical Pleistocene vicariance and incongruence between nuclear and mtDNA markers

    PubMed Central

    2009-01-01

    Background The common vampire bat Desmodus rotundus is an excellent model organism for studying ecological vicariance in the Neotropics due to its broad geographic range and its preference for forested areas as roosting sites. With the objective of testing for Pleistocene ecological vicariance, we sequenced a mitocondrial DNA (mtDNA) marker and two nuclear markers (RAG2 and DRB) to try to understand how Pleistocene glaciations affected the distribution of intraspecific lineages in this bat. Results Five reciprocally monophyletic clades were evident in the mitochondrial gene tree, and in most cases with high bootstrap support: Central America (CA), Amazon and Cerrado (AMC), Pantanal (PAN), Northern Atlantic Forest (NAF) and Southern Atlantic Forest (SAF). The Atlantic forest clades formed a monophyletic clade with high bootstrap support, creating an east/west division for this species in South America. On the one hand, all coalescent and non-coalescent estimates point to a Pleistocene time of divergence between the clades. On the other hand, the nuclear markers showed extensive sharing of haplotypes between distant localities, a result compatible with male-biased gene flow. In order to test if the disparity between the mitochondrial and nuclear markers was due to the difference in mutation rate and effective size, we performed a coalescent simulation to examine the feasibility that, given the time of separation between the observed lineages, even with a gene flow rate close to zero, there would not be reciprocal monophyly for a neutral nuclear marker. We used the observed values of theta and an estimated mutation rate for the nuclear marker gene to perform 1000 iterations of the simulation. The results of this simulation were inconclusive: the number of iterations with and without reciprocal monophyly of one or more clades are similar. Conclusions We therefore conclude that the pattern exhibited by the common vampire bat, with marked geographical structure for a

  12. Integrated Networks.

    ERIC Educational Resources Information Center

    Robinovitz, Stewart

    1987-01-01

    A strategy for integrated data and voice networks implemented at the University of Michigan is described. These networks often use multi-technologies, multi-vendors, and multi-transmission media that will be fused into a single integrated network. Transmission media include twisted-pair wire, coaxial cable, fiber optics, and microwave. (Author/MLW)

  13. Integrated Learning

    ERIC Educational Resources Information Center

    Gnanakan, Ken

    2012-01-01

    This book upholds the idea of learning and education as a means to individual development and social empowerment. It presents a holistic picture, looking at learning as an integral part of one's social and physical life. Strongly differing from existing classroom perspectives, the book analyses integrated learning at its broadest possible…

  14. Integrative psychotherapy.

    PubMed

    Kozarić-Kovacić, Dragica

    2008-09-01

    The main purposes of the article are to present the history of integration in psychotherapy, the reasons of the development integrative approaches, and the approaches to integration in psychotherapy. Three approaches to integration in psychotherapy exist: theoretical integration, theoretical eclecticism, and common factors in different psychotherapeutic trends. In integrative psychotherapy, the basic epistemology, theory, and clinical practice are based on the phenomenology, field theory, holism, dialogue, and co-creation of dialogue in the therapeutic relationship. The main criticism is that integrative psychotherapy suffers from confusion and many unresolved controversies. It is difficult to theoretically and methodologically define the clinically applied model that is based on such a different epistemological and theoretical presumptions. Integrative psychotherapy is a synthesis of humanistic psychotherapy, object relations theory, and psychoanalytical self psychology. It focuses on the dynamics and potentials of human relationships, with a goal of changing the relations and understanding internal and external resistances. The process of integrative psychotherapy is primarily focused on the developmental-relational model and co-creation of psychotherapeutic relationship as a single interactive event, which is not unilateral, but rather a joint endeavor by both the therapist and the patient/client. The need for a relationship is an important human need and represents a process of attunement that occurs as a response to the need for a relationship, a unique interpersonal contact between two people. If this need is not met, it manifests with the different feelings and various defenses. To meet this need, we need to have another person with whom we can establish a sensitive, attuned relationship. Thus, the therapist becomes this person who tries to supplement what the person did not receive. Neuroscience can be a source of integration through different therapies. We

  15. Trichinella spiralis mtDNA: a nematode mitochondrial genome that encodes a putative ATP8 and normally structured tRNAS and has a gene arrangement relatable to those of coelomate metazoans.

    PubMed Central

    Lavrov, D V; Brown, W M

    2001-01-01

    The complete mitochondrial DNA (mtDNA) of the nematode Trichinella spiralis has been amplified in four overlapping fragments and 16,656 bp of its sequence has been determined. This sequence contains the 37 genes typical of metazoan mtDNAs, including a putative atp8, which is absent from all other nematode mtDNAs examined. The genes are transcribed from both mtDNA strands and have an arrangement relatable to those of coelomate metazoans, but not to those of secernentean nematodes. All protein genes appear to initiate with ATN codons, typical for metazoans. Neither TTG nor GTT start codons, inferred for several genes of other nematodes, were found. The 22 T. spiralis tRNA genes fall into three categories: (i) those with the potential to form conventional "cloverleaf" secondary structures, (ii) those with TPsiC arm + variable arm replacement loops, and (iii) those with DHU-arm replacement loops. Mt-tRNA(R) has a 5'-UCG-3' anticodon, as in most other metazoans, instead of the very unusual 5'-ACG-3' present in the secernentean nematodes. The sequence also contains a large repeat region that is polymorphic in size at the population and/or individual level. PMID:11156984

  16. [The Dynamics of the Composition of mtDNA Haplotypes of the Ancient Population of the Altai Mountains from the Early Bronze Age (3rd Millennium BC) to the Iron Age (2nd-1st Centuries BC)].

    PubMed

    Gubina, M A; Kulikov, I V; Babenko, V N; Chikisheva, T A; Romaschenko, A G; Voevoda, M I; Molodin, V I

    2016-01-01

    The mtDNA polymorphism in representatives of various archaeological cultures of the Developed Bronze Age, Early Scythian, and Hunnish-Sarmatian periods was analyzed (N = 34). It detected the dominance of Western-Eurasian haplotypes (70.6%) in mtDNA samples from the representatives of the ancient population of the Early Bronze Age--Iron Age on the territory of Altai Mountains. Since the 8th to the 7th centuries BC, a sharp increase was revealed in the Eastern-Eurasian haplogroups A, D, C, andZ (43.75%) as compared to previous cultures (16.7%). The presence of haplotype 223-242-290-319 of haplogroup A8 in Dolgans, Itelmens, Evens, Koryaks, and Yakuts indicates the possible long-term presence of its carriers in areas inhabited by these populations. The prevalence of Western-Eurasian haplotypes is observed not only in the Altai Mountains but also in Central Asia (Kazakhstan) and the South of the Krasnoyarsk Krai. All of the three studied samples from the Western-Eurasian haplogroups were revealed to contain U, H, T, and HV. The ubiquitous presence of haplotypes of haplogroup H and some haplogroups of cluster U (U5al, U4, U2e, and K) in the vast territory from the Yenisei River basin to the Atlantic Ocean may indicate the direction of human settlement, which most likely occurred in the Paleolithic Period from Central Asia.

  17. Integrated diagnostics

    NASA Technical Reports Server (NTRS)

    Hunthausen, Roger J.

    1988-01-01

    Recently completed projects in which advanced diagnostic concepts were explored and/or demonstrated are summarized. The projects begin with the design of integrated diagnostics for the Army's new gas turbine engines, and advance to the application of integrated diagnostics to other aircraft subsystems. Finally, a recent project is discussed which ties together subsystem fault monitoring and diagnostics with a more complete picture of flight domain knowledge.

  18. Feedback Integrators

    NASA Astrophysics Data System (ADS)

    Chang, Dong Eui; Jiménez, Fernando; Perlmutter, Matthew

    2016-12-01

    A new method is proposed to numerically integrate a dynamical system on a manifold such that the trajectory stably remains on the manifold and preserves the first integrals of the system. The idea is that given an initial point in the manifold we extend the dynamics from the manifold to its ambient Euclidean space and then modify the dynamics outside the intersection of the manifold and the level sets of the first integrals containing the initial point such that the intersection becomes a unique local attractor of the resultant dynamics. While the modified dynamics theoretically produces the same trajectory as the original dynamics, it yields a numerical trajectory that stably remains on the manifold and preserves the first integrals. The big merit of our method is that the modified dynamics can be integrated with any ordinary numerical integrator such as Euler or Runge-Kutta. We illustrate this method by applying it to three famous problems: the free rigid body, the Kepler problem and a perturbed Kepler problem with rotational symmetry. We also carry out simulation studies to demonstrate the excellence of our method and make comparisons with the standard projection method, a splitting method and Störmer-Verlet schemes.

  19. Classical integrability

    NASA Astrophysics Data System (ADS)

    Torrielli, Alessandro

    2016-08-01

    We review some essential aspects of classically integrable systems. The detailed outline of the sections consists of: 1. Introduction and motivation, with historical remarks; 2. Liouville theorem and action-angle variables, with examples (harmonic oscillator, Kepler problem); 3. Algebraic tools: Lax pairs, monodromy and transfer matrices, classical r-matrices and exchange relations, non-ultralocal Poisson brackets, with examples (non-linear Schrödinger model, principal chiral field); 4. Features of classical r-matrices: Belavin-Drinfeld theorems, analyticity properties, and lift of the classical structures to quantum groups; 5. Classical inverse scattering method to solve integrable differential equations: soliton solutions, spectral properties and the Gel’fand-Levitan-Marchenko equation, with examples (KdV equation, Sine-Gordon model). Prepared for the Durham Young Researchers Integrability School, organised by the GATIS network. This is part of a collection of lecture notes.

  20. The Integrated Hazard Analysis Integrator

    NASA Technical Reports Server (NTRS)

    Morris, A. Terry; Massie, Michael J.

    2009-01-01

    Hazard analysis addresses hazards that arise in the design, development, manufacturing, construction, facilities, transportation, operations and disposal activities associated with hardware, software, maintenance, operations and environments. An integrated hazard is an event or condition that is caused by or controlled by multiple systems, elements, or subsystems. Integrated hazard analysis (IHA) is especially daunting and ambitious for large, complex systems such as NASA s Constellation program which incorporates program, systems and element components that impact others (International Space Station, public, International Partners, etc.). An appropriate IHA should identify all hazards, causes, controls and verifications used to mitigate the risk of catastrophic loss of crew, vehicle and/or mission. Unfortunately, in the current age of increased technology dependence, there is the tendency to sometimes overlook the necessary and sufficient qualifications of the integrator, that is, the person/team that identifies the parts, analyzes the architectural structure, aligns the analysis with the program plan and then communicates/coordinates with large and small components, each contributing necessary hardware, software and/or information to prevent catastrophic loss. As viewed from both Challenger and Columbia accidents, lack of appropriate communication, management errors and lack of resources dedicated to safety were cited as major contributors to these fatalities. From the accident reports, it would appear that the organizational impact of managers, integrators and safety personnel contributes more significantly to mission success and mission failure than purely technological components. If this is so, then organizations who sincerely desire mission success must put as much effort in selecting managers and integrators as they do when designing the hardware, writing the software code and analyzing competitive proposals. This paper will discuss the necessary and

  1. Numerical Integration

    ERIC Educational Resources Information Center

    Sozio, Gerry

    2009-01-01

    Senior secondary students cover numerical integration techniques in their mathematics courses. In particular, students would be familiar with the "midpoint rule," the elementary "trapezoidal rule" and "Simpson's rule." This article derives these techniques by methods which secondary students may not be familiar with and an approach that…

  2. Information Integrity

    ERIC Educational Resources Information Center

    Graves, Eric

    2013-01-01

    This dissertation introduces the concept of Information Integrity, which is the detection and possible correction of information manipulation by any intermediary node in a communication system. As networks continue to grow in complexity, information theoretic security has failed to keep pace. As a result many parties whom want to communicate,…

  3. Conservation genetics of high-arctic Gull species at risk: I. Diversity in the mtDNA control region of circumpolar populations of the Endangered Ivory Gull (Pagophila eburnea).

    PubMed

    Royston, Stephanie R; Carr, Steven M

    2016-11-01

    The high-arctic Ivory Gull (Pagophila eburnea) has recently undergone a sharp decline in numbers, and in Canada it is listed as "Endangered" under the Species-At-Risk Act. To test for circumpolar genetic distinctiveness, we examined 264 bp of the mtDNA Control Region Domain I from 127 museum specimens collected during the breeding season from northern Canada, Greenland, and Norway, and during the non-breeding season from adjacent overwintering grounds in Canada, Greenland, and a disjunct area in Alaska adjacent to the Bering Sea. Partition of genetic variance according to various phylogeographic and breeding ground models indicates no strong population structure, except that Alaska birds are consistently differentiated from other locations, and there are significant temporal shifts in haplotype frequencies. The evidence suggests that Ivory Gulls in Canada, Greenland, and Norway are a single genetic entity, in contrast to Alaska birds, which may represent a distinctive Siberian population.

  4. Integrated nanocatalysts.

    PubMed

    Zeng, Hua Chun

    2013-02-19

    Despite significant advancements in catalysis research, the prevailing catalyst technology remains largely an art rather than a science. Rapid development in the fields of nanotechnology and materials chemistry in the past few decades, however, provides us with a new capacity to re-examine existing catalyst design and processing methods. In recent years, "nanocatalysts" has become a term often used by the materials chemistry and catalysis community. It refers to heterogeneous catalysts at nanoscale dimensions. Similar to homogeneous catalysts, freestanding (unsupported) nanocatalysts are difficult to separate after use. Because of their small sizes, they are also likely to be cytotoxic and pose a threat to the environment and therefore may not be practical for industrial use. On the other hand, if they are supported on ordinary catalyst carriers, the nanocatalysts would then revert to act as conventional heterogeneous catalysts, since chemists have known active metal clusters or oxide particles in the nanoscale regime long before the nanotechnology era. To resolve this problem, we need new research directions and synthetic strategies. Important advancements in catalysis research now allow chemists to prepare catalytic materials with greater precision. By controlling particle composition, structure, shape, and dimension, researchers can move into the next phase of catalyst development if they can bridge these old and new technologies. In this regard, one way seems to be to integrate active nanostructured catalysts with boundary-defined catalyst supports that are "not-so-nano" in dimension. However, these supports still have available hierarchical pores and cavity spaces. In principle, these devices keep the essence of traditional "catalyst-plus-support" type systems. They also have the advantages of nanoscale engineering, which involves both high level design and integration processes in their fabrication. Besides this, the active components in these devices are

  5. Human maternal heritage in Andalusia (Spain): its composition reveals high internal complexity and distinctive influences of mtDNA haplogroups U6 and L in the western and eastern side of region

    PubMed Central

    2014-01-01

    Background The archeology and history of the ancient Mediterranean have shown that this sea has been a permeable obstacle to human migration. Multiple cultural exchanges around the Mediterranean have taken place with presumably population admixtures. A gravitational territory of those migrations has been the Iberian Peninsula. Here we present a comprehensive analysis of the maternal gene pool, by means of control region sequencing and PCR-RFLP typing, of autochthonous Andalusians originating from the coastal provinces of Huelva and Granada, located respectively in the west and the east of the region. Results The mtDNA haplogroup composition of these two southern Spanish populations has revealed a wide spectrum of haplogroups from different geographical origins. The registered frequencies of Eurasian markers, together with the high incidence and diversification of African maternal lineages (15% of the total mitochondrial variability) among Huelva Andalusians when compared to its eastwards relatives of Granada and other Iberian populations, constitute relevant findings unknown up-to-date on the characteristics of mtDNA within Andalusia that testifies a female population substructure. Therefore, Andalusia must not be considered a single, unique population. Conclusions The maternal legacy among Andalusians reflects distinctive local histories, pointing out the role of the westernmost territory of Peninsular Spain as a noticeable recipient of multiple and diverse human migrations. The obtained results underline the necessity of further research on genetic relationships in both sides of the western Mediterranean, using carefully collected samples from autochthonous individuals. Many studies have focused on recent North African gene flow towards Iberia, yet scientific attention should be now directed to thoroughly study the introduction of European genes in northwest Africa across the sea, in order to determine its magnitude, timescale and methods, and to compare them to

  6. Integrated Fluorescence

    NASA Technical Reports Server (NTRS)

    Tuma, Margaret (Inventor); Gruhlke, Russell W. (Inventor)

    1998-01-01

    A detection method is integrated with a filtering method and an enhancement method to create a fluorescence sensor that can be miniaturized. The fluorescence sensor comprises a thin film geometry including a waveguide layer, a metal film layer and sensor layer. The thin film geometry of the fluorescence sensor allows the detection of fluorescent radiation over a narrow wavelength interval. This enables wavelength discrimination and eliminates the detection of unwanted light from unknown or spurious sources.

  7. The Agrocybe aegerita mitochondrial genome contains two inverted repeats of the nad4 gene arisen by duplication on both sides of a linear plasmid integration site.

    PubMed

    Ferandon, C; Chatel, S El Kirat; Castandet, B; Castroviejo, M; Barroso, G

    2008-03-01

    The Agrocybe aegerita mitochondrial genome possesses two polB genes with linear plasmid origin. The cloning and sequencing of the regions flanking Aa-polB P1 revealed two large inverted repeats (higher than 2421 nt) separated by a single copy region of 5834 nt. Both repeats contain identical copies of the nad4 gene. The single copy region contains two disrupted genes with plasmid origin Aa-polB P1 and a small ORF homologous to a small gene described in two basidiomycete linear plasmids. The phylogenetic analyses argue in favor of a same plasmid origin for both genes but, surprisingly, these genes were separated by a mitochondrial tRNA-Met. Both strands of the complete region containing the two nad4 inverted copies and the tRNA-Met appear to be transcribed on large polycistronic mRNAs. A model summarizing the events that would have occurred is proposed: (1) capture of the tRNA by the plasmid before its integration in the mtDNA or acquisition of the tRNA gene by recombination after the plasmid integration, (2) integration of the plasmid in the mtDNA, accompanied by a large duplication containing the nad4 gene and (3) erosion of the plasmid sequences by large deletions and mutations.

  8. ACCELERATION INTEGRATOR

    DOEpatents

    Pope, K.E.

    1958-01-01

    This patent relates to an improved acceleration integrator and more particularly to apparatus of this nature which is gyrostabilized. The device may be used to sense the attainment by an airborne vehicle of a predetermined velocitv or distance along a given vector path. In its broad aspects, the acceleration integrator utilizes a magnetized element rotatable driven by a synchronous motor and having a cylin drical flux gap and a restrained eddy- current drag cap deposed to move into the gap. The angular velocity imparted to the rotatable cap shaft is transmitted in a positive manner to the magnetized element through a servo feedback loop. The resultant angular velocity of tae cap is proportional to the acceleration of the housing in this manner and means may be used to measure the velocity and operate switches at a pre-set magnitude. To make the above-described dcvice sensitive to acceleration in only one direction the magnetized element forms the spinning inertia element of a free gyroscope, and the outer housing functions as a gimbal of a gyroscope.

  9. [Genetic variation and phylogeography of the bank vole (Clethrionomys glareolus, Arvicolinae, Rodentia) in Russia with special reference to the introgression of the mtDNA of a closely related species, red-backed vole (C. rutilus)].

    PubMed

    Abramson, N I; Rodchenkova, E N; Kostygov, A Iu

    2009-05-01

    Totally, 294 bank voles (Clethrionomys glareolus) and 18 red-backed voles (C. rutilus) from 62 sites of European Russia were studied. Incomplete sequences (967 bp) of the mitochondrial cytochrome b gene were determined for 93 C. glareolus individuals from 56 sites and 18 C. rutilus individuals from the same habitats. Analysis of the cytochrome b gene variation has demonstrated that practically the entire European part of Russia, Ural, and a considerable part of Western Europe are inhabited by bank voles of the same phylogroup, displaying an extremely low genetic differentiation. Our data suggest that C. glareolus very rapidly colonized over the presently occupied territory in the post-Pleistocene period from no more than two (central European and western European) refugia for ancestral populations with a small efficient size. PCR typing of the mitochondrial cytochrome b gene allowed us to assess the scale of mtDNA introgression from a closely related species, C. rutilus, and to outline the geographical zone of this introgression. Comparison with the red-backed vole haplotypes in the habitats shared by both species favors the hypothesis of an ancient hybridization event (mid-Holocene) and a subsequent introgression. These results suggest that the hybridization took place in the southern and middle Pre-Ural region.

  10. Phylogenetic analysis of the Pacific cutthroat trout (Oncorhynchus clarki ssp.: Salmonidae) based on partial mtDNA ND4 sequences: a closer look at the highly fragmented inland species.

    PubMed

    Wilson, Wade D; Turner, Thomas F

    2009-08-01

    The genus Oncorhynchus includes Pacific salmon and trout (anadromous and land-locked) species of the western United States and Mexico. All species and subspecies in this group are threatened, endangered, sensitive, or species of conservation concern in portions of their native ranges. To examine the relationships of the species within Oncorhynchus we sequenced a 768 bp fragment of the protein-encoding ND4 mtDNA region. We included all six recognized subspecies of O. clarki (cutthroat trout), O. gilaegilae (Gila trout) and O. g. apache (Apache trout). Gene trees from likelihood and Bayesian phylogenetic analyses revealed that Salvelinus was the sister group to Oncorhynchus, and as expected based on previous studies, O. clarki was sister to a clade that consisted of O. mykiss plus O. g. gilae and O. g. apache. Within the cutthroat clade (O. clarki), the coastal form O. c. clarki was basal with the Rio Grande cutthroat (O. c. virginalis) most derived. Divergence dating based on a fossil calibration molecular clock showed the oldest clade (mean node age) was O. masou ssp., which diverged roughly 7.6 MYA. Highest probability density intervals for divergence of O. masou overlapped with divergence (6.3 MYA) of Pacific salmon clades ((O. gorbuscha + O. nerka) and (O. tshawytscha + O. kisutch)). The Pacific trout clade ((O. mykiss + O. gilae ssp.) + (O. clarki ssp.)) diverged from the Pacific salmon around 6.3 MYA, with most of the diversification within the O. clarki clade occurring in the last 1 MY.

  11. The Genetic Integrity of the Ex Situ Population of the European Wildcat (Felis silvestris silvestris) Is Seriously Threatened by Introgression from Domestic Cats (Felis silvestris catus)

    PubMed Central

    Witzenberger, Kathrin A.; Hochkirch, Axel

    2014-01-01

    Studies on the genetic diversity and relatedness of zoo populations are crucial for implementing successful breeding programmes. The European wildcat, Felis s. silvestris, is subject to intensive conservation measures, including captive breeding and reintroduction. We here present the first systematic genetic analysis of the captive population of Felis s. silvestris in comparison with a natural wild population. We used microsatellites and mtDNA sequencing to assess genetic diversity, structure and integrity of the ex situ population. Our results show that the ex situ population of the European wildcat is highly structured and that it has a higher genetic diversity than the studied wild population. Some genetic clusters matched the breeding lines of certain zoos or groups of zoos that often exchanged individuals. Two mitochondrial haplotype groups were detected in the in situ populations, one of which was closely related to the most common haplotype found in domestic cats, suggesting past introgression in the wild. Although native haplotypes were also found in the captive population, the majority (68%) of captive individuals shared a common mtDNA haplotype with the domestic cat (Felis s. catus). Only six captive individuals (7.7%) were assigned as wildcats in the STRUCTURE analysis (at K = 2), two of which had domestic cat mtDNA haplotypes and only two captive individuals were assigned as purebred wildcats by NewHybrids. These results suggest that the high genetic diversity of the captive population has been caused by admixture with domestic cats. Therefore, the captive population cannot be recommended for further breeding and reintroduction. PMID:25162450

  12. The genetic integrity of the ex situ population of the European wildcat (Felis silvestris silvestris) is seriously threatened by introgression from domestic cats (Felis silvestris catus).

    PubMed

    Witzenberger, Kathrin A; Hochkirch, Axel

    2014-01-01

    Studies on the genetic diversity and relatedness of zoo populations are crucial for implementing successful breeding programmes. The European wildcat, Felis s. silvestris, is subject to intensive conservation measures, including captive breeding and reintroduction. We here present the first systematic genetic analysis of the captive population of Felis s. silvestris in comparison with a natural wild population. We used microsatellites and mtDNA sequencing to assess genetic diversity, structure and integrity of the ex situ population. Our results show that the ex situ population of the European wildcat is highly structured and that it has a higher genetic diversity than the studied wild population. Some genetic clusters matched the breeding lines of certain zoos or groups of zoos that often exchanged individuals. Two mitochondrial haplotype groups were detected in the in situ populations, one of which was closely related to the most common haplotype found in domestic cats, suggesting past introgression in the wild. Although native haplotypes were also found in the captive population, the majority (68%) of captive individuals shared a common mtDNA haplotype with the domestic cat (Felis s. catus). Only six captive individuals (7.7%) were assigned as wildcats in the STRUCTURE analysis (at K = 2), two of which had domestic cat mtDNA haplotypes and only two captive individuals were assigned as purebred wildcats by NewHybrids. These results suggest that the high genetic diversity of the captive population has been caused by admixture with domestic cats. Therefore, the captive population cannot be recommended for further breeding and reintroduction.

  13. Integrating mitochondriomics in children’s environmental health

    PubMed Central

    Brunst, Kelly J.; Baccarelli, Andrea A.; Wright, Rosalind J.

    2016-01-01

    The amount of scientific research linking environmental exposures and childhood health outcomes continues to grow; yet few studies have teased out the mechanisms involved in environmentally-induced diseases. Cells can respond to environmental stressors in many ways: inducing oxidative stress/inflammation, changes in energy production and epigenetic alterations. Mitochondria, tiny organelles that each retains their own DNA, are exquisitely sensitive to environmental insults and are thought to be central players in these pathways. While it is intuitive that mitochondria play an important role in disease processes, given that every cell of our body is dependent on energy metabolism, it is less clear how environmental exposures impact mitochondrial mechanisms that may lead to enhanced risk of disease. Many of the effects of the environment are initiated in utero and integrating mitochondriomics into children’s environmental health studies is a critical priority. This review will highlight (i) the importance of exploring environmental mitochondriomics in children’s environmental health, (ii) why environmental mitochondriomics is well suited to biomarker development in this context, and (iii) how molecular and epigenetic changes in mitochondria and mitochondrial DNA (mtDNA) may reflect exposures linked to childhood health outcomes. PMID:26046650

  14. RECQL4 LOCALIZES TO MITOCHONDRIA AND PRESERVES MITOCHONDRIAL DNA INTEGRITY

    PubMed Central

    Croteau, Deborah L.; Rossi, Marie L.; Canugovi, Chandrika; Tian, Jane; Sykora, Peter; Ramamoorthy, Mahesh; Wang, ZhengMing; Singh, Dharmendra Kumar; Akbari, Mansour; Kasiviswanathan, Rajesh; Copeland, William C.; Bohr, Vilhelm A.

    2012-01-01

    SUMMARY RECQL4 is associated with Rothmund-Thomson Syndrome (RTS), a rare autosomal recessive disorder characterized by premature aging, genomic instability and cancer predisposition. RECQL4 is a member of the RecQ-helicase family, and has many similarities to WRN protein, which is also implicated in premature aging. There is no information about whether any of the RecQ helicases play roles in mitochondrial biogenesis, which is strongly implicated in the aging process. Here, we used microscopy to visualize RECQL4 in mitochondria. Fractionation of human and mouse cells also showed that RECQL4 was present in mitochondria. Q-PCR amplification of mitochondrial DNA demonstrated that mtDNA damage accumulated in RECQL4-deficient cells. Microarray analysis suggested that mitochondrial bioenergetic pathways might be affected in RTS. Measurements of mitochondrial bioenergetics showed a reduction in the mitochondrial reserve capacity after lentiviral knockdown of RECQL4 in two different primary cell lines. Additionally, biochemical assays with RECQL4, mitochondrial transcription factor A and mitochondrial DNA polymerase γ showed that the polymerase inhibited RECQL4’s helicase activity. RECQL4 is the first 3′ to 5′ RecQ helicase to be found in both human and mouse mitochondria and the loss of RECQL4 alters mitochondrial integrity. PMID:22296597

  15. Evaluating Simultaneous Integrals

    ERIC Educational Resources Information Center

    Kwong, Harris

    2012-01-01

    Many integrals require two successive applications of integration by parts. During the process, another integral of similar type is often invoked. We propose a method which can integrate these two integrals simultaneously. All we need is to solve a linear system of equations.

  16. Thermionic integrated circuits

    SciTech Connect

    MacRoberts, M.; Brown, D.R.; Dooley, R.; Lemons, R.; Lynn, D.; McCormick, B.; Mombourquette, C.; Sinah, D.

    1986-01-01

    Thermionic integrated circuits combine vacuum-tube technology with integrated-circuit techniques to form integrated vacuum circuits. These circuits are capable of extended operation in both high-temperature and high-radiation environments.

  17. Relations Between Hyperelliptic Integrals

    NASA Astrophysics Data System (ADS)

    Pakuliak, S.; Perelomov, A.

    A simple property of the integrals over the hyperelliptic surfaces of arbitrary genus is observed. Namely, the derivatives of these integrals with respect to the branching points are given by the linear combination of the same integrals. We check that this property is responsible for the solution to the level zero Knizhnik-Zamolodchikov equation given in terms of hyperelliptic integrals.

  18. Slimplectic Integrators: Variational Integrators for Nonconservative systems

    NASA Astrophysics Data System (ADS)

    Tsang, David

    2016-05-01

    Symplectic integrators are widely used for long-term integration of conservative astrophysical problems due to their ability to preserve the constants of motion; however, they cannot in general be applied in the presence of nonconservative interactions. Here we present the “slimplectic” integrator, a new type of numerical integrator that shares many of the benefits of traditional symplectic integrators yet is applicable to general nonconservative systems. We utilize a fixed-time-step variational integrator formalism applied to a newly developed principle of stationary nonconservative action (Galley, 2013, Galley et al 2014). As a result, the generalized momenta and energy (Noether current) evolutions are well-tracked. We discuss several example systems, including damped harmonic oscillators, Poynting-Robertson drag, and gravitational radiation reaction, by utilizing our new publicly available code to demonstrate the slimplectic integrator algorithm. Slimplectic integrators are well-suited for integrations of systems where nonconservative effects play an important role in the long-term dynamical evolution. As such they are particularly appropriate for cosmological or celestial N-body dynamics problems where nonconservative interactions, e.g., gas interactions or dissipative tides, can play an important role.

  19. Information integration without awareness.

    PubMed

    Mudrik, Liad; Faivre, Nathan; Koch, Christof

    2014-09-01

    Information integration and consciousness are closely related, if not interdependent. But, what exactly is the nature of their relation? Which forms of integration require consciousness? Here, we examine the recent experimental literature with respect to perceptual and cognitive integration of spatiotemporal, multisensory, semantic, and novel information. We suggest that, whereas some integrative processes can occur without awareness, their scope is limited to smaller integration windows, to simpler associations, or to ones that were previously acquired consciously. This challenges previous claims that consciousness of some content is necessary for its integration; yet it also suggests that consciousness holds an enabling role in establishing integrative mechanisms that can later operate unconsciously, and in allowing wider-range integration, over bigger semantic, spatiotemporal, and sensory integration windows.

  20. Buried waste integrated demonstration technology integration process

    SciTech Connect

    Ferguson, J.S.; Ferguson, J.E.

    1992-04-01

    A Technology integration Process was developed for the Idaho National Energy Laboratories (INEL) Buried Waste Integrated Demonstration (BWID) Program to facilitate the transfer of technology and knowledge from industry, universities, and other Federal agencies into the BWID; to successfully transfer demonstrated technology and knowledge from the BWID to industry, universities, and other Federal agencies; and to share demonstrated technologies and knowledge between Integrated Demonstrations and other Department of Energy (DOE) spread throughout the DOE Complex. This document also details specific methods and tools for integrating and transferring technologies into or out of the BWID program. The document provides background on the BWID program and technology development needs, demonstrates the direction of technology transfer, illustrates current processes for this transfer, and lists points of contact for prospective participants in the BWID technology transfer efforts. The Technology Integration Process was prepared to ensure compliance with the requirements of DOE`s Office of Technology Development (OTD).

  1. Buried waste integrated demonstration technology integration process

    SciTech Connect

    Ferguson, J.S.; Ferguson, J.E.

    1992-04-01

    A Technology integration Process was developed for the Idaho National Energy Laboratories (INEL) Buried Waste Integrated Demonstration (BWID) Program to facilitate the transfer of technology and knowledge from industry, universities, and other Federal agencies into the BWID; to successfully transfer demonstrated technology and knowledge from the BWID to industry, universities, and other Federal agencies; and to share demonstrated technologies and knowledge between Integrated Demonstrations and other Department of Energy (DOE) spread throughout the DOE Complex. This document also details specific methods and tools for integrating and transferring technologies into or out of the BWID program. The document provides background on the BWID program and technology development needs, demonstrates the direction of technology transfer, illustrates current processes for this transfer, and lists points of contact for prospective participants in the BWID technology transfer efforts. The Technology Integration Process was prepared to ensure compliance with the requirements of DOE's Office of Technology Development (OTD).

  2. Integrated design of integral liquid fuel ramjet

    NASA Astrophysics Data System (ADS)

    Gu, Liangxian; Yang, Jianxin; Ma, Jia; Liu, Jingchun

    1993-04-01

    Integrated design of integral liquid fuel ramjet (ILFR) is regarded as a system of the combination of missile and ILFR, which aims at obtaining the optimum performance of the system and optimizing the parameters of both missile and ramjet. In this paper, supersonic cruise missile of medium range is taken as a calculation example. In accordance with the features of integrated ramjet, the integrated design of missile and integral ramjet are discussed here. Missile configuration and ramjet parameters are optimized and then the maximum range is obtained based on two typical cases in medium and low height cruising. Some problems related to choosing missile and ramjet parameters are also, discussed and analyzed for application in different cruise heights.

  3. Alternative and Integrative Medicine

    MedlinePlus

    ... Alternative & Integrative Medicine Clinical Trials GBM AGILE TTFields – Optune™ Brain Tumor Treatment Locations Treatment Side Effects & their ... Alternative & Integrative Medicine Clinical Trials GBM AGILE TTFields – Optune™ Brain Tumor Treatment Locations Treatment Side Effects & their ...

  4. The universal path integral

    NASA Astrophysics Data System (ADS)

    Lloyd, Seth; Dreyer, Olaf

    2016-02-01

    Path integrals calculate probabilities by summing over classical configurations of variables such as fields, assigning each configuration a phase equal to the action of that configuration. This paper defines a universal path integral, which sums over all computable structures. This path integral contains as sub-integrals all possible computable path integrals, including those of field theory, the standard model of elementary particles, discrete models of quantum gravity, string theory, etc. The universal path integral possesses a well-defined measure that guarantees its finiteness. The probabilities for events corresponding to sub-integrals can be calculated using the method of decoherent histories. The universal path integral supports a quantum theory of the universe in which the world that we see around us arises out of the interference between all computable structures.

  5. Discovering Integrals with Geometry.

    ERIC Educational Resources Information Center

    Alexopoulos, John; Barb, Cynthia

    2001-01-01

    Presents problems to find the integrals of logarithmic and inverse trigonometric functions early in the calculus sequence by using the Fundamental Theorem of Calculus and the concept of area, and without the use of integration by parts. (Author/ASK)

  6. Two Related Parametric Integrals

    ERIC Educational Resources Information Center

    Dana-Picard, T.

    2007-01-01

    Two related sequences of definite integrals are considered. By mixing hand-work, computer algebra system assistance and websurfing, fine connections can be studied between integrals and a couple of interesting sequences of integers. (Contains 4 tables.)

  7. Boolean integral calculus

    NASA Technical Reports Server (NTRS)

    Tucker, Jerry H.; Tapia, Moiez A.; Bennett, A. Wayne

    1988-01-01

    The concept of Boolean integration is developed, and different Boolean integral operators are introduced. Given the changes in a desired function in terms of the changes in its arguments, the ways of 'integrating' (i.e. realizing) such a function, if it exists, are presented. The necessary and sufficient conditions for integrating, in different senses, the expression specifying the changes are obtained. Boolean calculus has applications in the design of logic circuits and in fault analysis.

  8. Integrated Modeling Systems

    DTIC Science & Technology

    1989-01-01

    Summer 1979). WMSI Working Paper No. 291A. 173 Dyer , J. and R. Sarin. "Measurable Multiattribute Value Functions," Operations Research. 27:4 (July...J. McCall. "Expected Utility Maximizing Job Search," Chapter 7 of Studies in the Economics of Search, 1979, North-Holland. WMSI Working Paper No. 274...model integration, solver integration, and integration of various utilities . Model integration is further divided into four subtypes based on a four-level

  9. Integrated optics technology study

    NASA Technical Reports Server (NTRS)

    Chen, B.

    1982-01-01

    The materials and processes available for the fabrication of single mode integrated electrooptical components are described. Issues included in the study are: (1) host material and orientation, (2) waveguide formation, (3) optical loss mechanisms, (4) wavelength selection, (5) polarization effects and control, (6) laser to integrated optics coupling,(7) fiber optic waveguides to integrated optics coupling, (8) souces, (9) detectors. The best materials, technology and processes for fabrication of integrated optical components for communications and fiber gyro applications are recommended.

  10. Enumeration of Integral Tetrahedra

    NASA Astrophysics Data System (ADS)

    Kurz, Sascha

    2007-09-01

    We determine the number of integral tetrahedra with diameter d, up to isomorphism, for all d<=1000, via computer enumeration. We give an algorithm that enumerates the integral tetrahedra with diameter at most d in O(d^5) time and an algorithm that can check the canonicity of a given integral tetrahedron with at most 6 integer comparisons. For the number of isomorphism classes of integral 4x4 matrices with diameter d fulfilling the triangle inequalities we derive an exact formula.

  11. Integrated optics technology study

    NASA Technical Reports Server (NTRS)

    Chen, B.; Findakly, T.; Innarella, R.

    1982-01-01

    The status and near term potential of materials and processes available for the fabrication of single mode integrated electro-optical components are discussed. Issues discussed are host material and orientation, waveguide formation, optical loss mechanisms, wavelength selection, polarization effects and control, laser to integrated optics coupling fiber optic waveguides to integrated optics coupling, sources, and detectors. Recommendations of the best materials, technology, and processes for fabrication of integrated optical components for communications and fiber gyro applications are given.

  12. Optimizing Computer Technology Integration

    ERIC Educational Resources Information Center

    Dillon-Marable, Elizabeth; Valentine, Thomas

    2006-01-01

    The purpose of this study was to better understand what optimal computer technology integration looks like in adult basic skills education (ABSE). One question guided the research: How is computer technology integration best conceptualized and measured? The study used the Delphi method to map the construct of computer technology integration and…

  13. Sledge-Hammer Integration

    ERIC Educational Resources Information Center

    Ahner, Henry

    2009-01-01

    Integration (here visualized as a pounding process) is mathematically realized by simple transformations, successively smoothing the bounding curve into a straight line and the region-to-be-integrated into an area-equivalent rectangle. The relationship to Riemann sums, and to the trapezoid and midpoint methods of numerical integration, is…

  14. Integrated Education. Feature Issue.

    ERIC Educational Resources Information Center

    York, Jennifer, Ed.; Vandercook, Terri, Ed.

    1988-01-01

    This "feature issue" provides various perspectives on a number of integrated education topics, including successful integration practices and strategies, the changing roles of teachers, the appropriate role of research, the history and future of integrated education, and the realization of dreams of life in the mainstream for children with severe…

  15. Parametric Differentiation and Integration

    ERIC Educational Resources Information Center

    Chen, Hongwei

    2009-01-01

    Parametric differentiation and integration under the integral sign constitutes a powerful technique for calculating integrals. However, this topic is generally not included in the undergraduate mathematics curriculum. In this note, we give a comprehensive review of this approach, and show how it can be systematically used to evaluate most of the…

  16. Integrating Writing and Mathematics

    ERIC Educational Resources Information Center

    Wilcox, Brad; Monroe, Eula Ewing

    2011-01-01

    Teachers often find it difficult to integrate writing and mathematics while honoring the integrity of both disciplines. In this article, the authors present two levels of integration that teachers may use as a starting point. The first level, writing without revision, can be worked into mathematics instruction quickly and readily. The second…

  17. Photonic Integrated Circuits

    NASA Technical Reports Server (NTRS)

    Merritt, Scott; Krainak, Michael

    2016-01-01

    Integrated photonics generally is the integration of multiple lithographically defined photonic and electronic components and devices (e.g. lasers, detectors, waveguides passive structures, modulators, electronic control and optical interconnects) on a single platform with nanometer-scale feature sizes. The development of photonic integrated circuits permits size, weight, power and cost reductions for spacecraft microprocessors, optical communication, processor buses, advanced data processing, and integrated optic science instrument optical systems, subsystems and components. This is particularly critical for small spacecraft platforms. We will give an overview of some NASA applications for integrated photonics.

  18. Faces of integration

    PubMed Central

    Williams, Paul; Sullivan, Helen

    2009-01-01

    Theme Two central themes permeate this paper—the interplay between structure and agency in integration processes and the extent to which this is mediated through sensemaking by individual actors. Case study The empirical base for the paper is provided by case study research from Wales which draws on examples of different types of integration in health and social care. The individual case studies highlight different interpretations of integration set against a background of the resources involved, processes employed and outcomes achieved. Discussion A wide ranging discussion exposes the complex interplay and dynamics between structural factors and the manner in which they enable or constrain integration, and individual actors realising their potential agency through leadership, professionalism and boundary spanning to influence outcomes. The importance of structure and agency complementing each other to determine effective integration is emphasised, together with the scope that is available for interpretation and meaning by individual actors within the contested discourse of integration. PMID:20087420

  19. SEMP Integration Project

    DTIC Science & Technology

    2006-05-24

    Prabhu R. 2000. Development of a methodology for selecting criteria and indicators of sustainable forest management: A case study on participatory ...integration framework development efforts focused on two dilemmas—integrating across field studies and relating science and practice. We summarize results from...areas, than to ecologically meaningful boundaries. 5. Discussion We sought to develop a consensus-based framework to guide the integration of varied

  20. Integrated Sensitivity Analysis Workflow

    SciTech Connect

    Friedman-Hill, Ernest J.; Hoffman, Edward L.; Gibson, Marcus J.; Clay, Robert L.

    2014-08-01

    Sensitivity analysis is a crucial element of rigorous engineering analysis, but performing such an analysis on a complex model is difficult and time consuming. The mission of the DART Workbench team at Sandia National Laboratories is to lower the barriers to adoption of advanced analysis tools through software integration. The integrated environment guides the engineer in the use of these integrated tools and greatly reduces the cycle time for engineering analysis.

  1. Path Integrals and Hamiltonians

    NASA Astrophysics Data System (ADS)

    Baaquie, Belal E.

    2014-03-01

    1. Synopsis; Part I. Fundamental Principles: 2. The mathematical structure of quantum mechanics; 3. Operators; 4. The Feynman path integral; 5. Hamiltonian mechanics; 6. Path integral quantization; Part II. Stochastic Processes: 7. Stochastic systems; Part III. Discrete Degrees of Freedom: 8. Ising model; 9. Ising model: magnetic field; 10. Fermions; Part IV. Quadratic Path Integrals: 11. Simple harmonic oscillators; 12. Gaussian path integrals; Part V. Action with Acceleration: 13. Acceleration Lagrangian; 14. Pseudo-Hermitian Euclidean Hamiltonian; 15. Non-Hermitian Hamiltonian: Jordan blocks; 16. The quartic potential: instantons; 17. Compact degrees of freedom; Index.

  2. Avionics systems integration technology

    NASA Technical Reports Server (NTRS)

    Stech, George; Williams, James R.

    1988-01-01

    A very dramatic and continuing explosion in digital electronics technology has been taking place in the last decade. The prudent and timely application of this technology will provide Army aviation the capability to prevail against a numerically superior enemy threat. The Army and NASA have exploited this technology explosion in the development and application of avionics systems integration technology for new and future aviation systems. A few selected Army avionics integration technology base efforts are discussed. Also discussed is the Avionics Integration Research Laboratory (AIRLAB) that NASA has established at Langley for research into the integration and validation of avionics systems, and evaluation of advanced technology in a total systems context.

  3. Designing for STEM Integration

    ERIC Educational Resources Information Center

    Berland, Leema K.

    2013-01-01

    We are increasingly seeing an emphasis on STEM integration in high school classrooms such that students will learn and apply relevant math and science content while simultaneously developing engineering habits of mind. However, research in both science education and engineering education suggests that this goal of truly integrating STEM is rife…

  4. Integration by Hyperbolic Substitution

    ERIC Educational Resources Information Center

    Price, David

    2012-01-01

    Mathematics teachers constantly encourage their students to think independently. The study of integration in calculus provides an excellent opportunity to encourage inventive investigation. In contrast to differentiation, which is predominately mechanical, integration is a more creative process. One such possibility is offered by the study of the…

  5. Integration in Hydraulics.

    ERIC Educational Resources Information Center

    Sworder, Steven C.

    This paper presents an application of integration to the field of hydraulics. An integral relation for the time required to drop the fluid contained in a cylindrical tank from one level to another using a hole in the tank wall is derived. Procedures for constructing the experimental equipment and procedures for determining the coefficient of…

  6. Hermeneutics of Integrative Knowledge.

    ERIC Educational Resources Information Center

    Shin, Un-chol

    This paper examines and compares the formation processes and structures of three types of integrative knowledge that in general represent natural sciences, social sciences, and humanities. These three types can be observed, respectively, in the philosophies of Michael Polanyi, Jurgen Habermas, and Paul Ricoeur. These types of integrative knowledge…

  7. Systems Integration (Fact Sheet)

    SciTech Connect

    DOE Solar Energy Technologies Program

    2011-10-13

    The Systems Integration (SI) subprogram works closely with industry, universities, and the national laboratories to overcome technical barriers to the large-scale deployment of solar technologies. To support these goals, the subprogram invests primarily in four areas: grid integration, technology validation, solar resource assessment, and balance of system development.

  8. Intelligent test integration system

    NASA Technical Reports Server (NTRS)

    Sztipanovits, J.; Padalkar, S.; Rodriguez-Moscoso, J.; Kawamura, K.; Purves, B.; Williams, R.; Biglari, H.

    1988-01-01

    A new test technology is described which was developed for space system integration. The ultimate purpose of the system is to support the automatic generation of test systems in real time, distributed computing environments. The Intelligent Test Integration System (ITIS) is a knowledge based layer above the traditional test system components which can generate complex test configurations from the specification of test scenarios.

  9. Integrity in Student Development

    ERIC Educational Resources Information Center

    Roberts, Dennis C.; Banta, Trudy W.

    2011-01-01

    The quest for integrity in practice and theory has been part of the evolution of student personnel work all the way back to the turn of the 20th century. This chapter seeks to take stock of the question of integrity in relation to one of the core knowledge bases used by those engaged in student affairs work today--student development. The authors…

  10. Systems Integration (Fact Sheet)

    SciTech Connect

    Not Available

    2011-10-01

    The Systems Integration (SI) subprogram works closely with industry, universities, and the national laboratories to overcome technical barriers to the large-scale deployment of solar technologies. To support these goals, the subprogram invests primarily in four areas: grid integration, technology validation, solar resource assessment, and balance of system development.

  11. System integration report

    NASA Technical Reports Server (NTRS)

    Badler, N. I.; Korein, J. D.; Meyer, C.; Manoochehri, K.; Rovins, J.; Beale, J.; Barr, B.

    1985-01-01

    Several areas that arise from the system integration issue were examined. Intersystem analysis is discussed as it relates to software development, shared data bases and interfaces between TEMPUS and PLAID, shaded graphics rendering systems, object design (BUILD), the TEMPUS animation system, anthropometric lab integration, ongoing TEMPUS support and maintenance, and the impact of UNIX and local workstations on the OSDS environment.

  12. ESPC Integrated Skill Diagnostics

    DTIC Science & Technology

    2015-09-30

    monitoring systems for gauging performance of the ESPC. This is an integral part of the overall ESPC goal of developing a global coupled system between...1 DISTRIBUTION STATEMENT A. Approved for public release; distribution is unlimited. ESPC Integrated Skill Diagnostics Maria Flatau Naval...quantitative skill metrics to assess the advancements in the Earth System Prediction Capability (ESPC). This work will also implement automated

  13. An Integrated Teaching Module.

    ERIC Educational Resources Information Center

    Samuel, Marie R.; Seiferth, Berniece B.

    This integrated teaching module provides elementary and junior high school teachers with a "hands-on" approach to studying the Anasazi Indian. Emphasis is on creative exploration that focuses on integrating art, music, poetry, writing, geography, dance, history, anthropology, sociology, and archaeology. Replicas of artifacts,…

  14. Integrated Modeling Environment

    NASA Technical Reports Server (NTRS)

    Mosier, Gary; Stone, Paul; Holtery, Christopher

    2006-01-01

    The Integrated Modeling Environment (IME) is a software system that establishes a centralized Web-based interface for integrating people (who may be geographically dispersed), processes, and data involved in a common engineering project. The IME includes software tools for life-cycle management, configuration management, visualization, and collaboration.

  15. Undulator Field Integral Measurements

    SciTech Connect

    Wolf, Zachary

    2010-12-07

    The LCLS undulator field integrals must be very small so that the beam trajectory slope and offset stay within tolerance. In order to make accurate measurements of the small field integrals, a long coil will be used. This note describes the design of the coil measurement system.

  16. Academic Research Integration System

    ERIC Educational Resources Information Center

    Surugiu, Iula; Velicano, Manole

    2008-01-01

    This paper comprises results concluding the research activity done so far regarding enhanced web services and system integration. The objective of the paper is to define the software architecture for a coherent framework and methodology for enhancing existing web services into an integrated system. This document presents the research work that has…

  17. Integrating Module - NEMS Documentation

    EIA Publications

    2014-01-01

    Provides an overview of the complete National Energy Modeling System (NEMS) model, and includes brief descriptions of the modules with which the Integrating Module interacts. The emphasis and focus, however, is on the structure and function of the Integrating Module of NEMS.

  18. The Fresnel Integrals Revisited

    ERIC Educational Resources Information Center

    Chen, Hongwei

    2009-01-01

    This note presents another elementary method to evaluate the Fresnel integrals. It is interesting to see that this technique is also strong enough to capture a number of pairs of parameter integrals. The main ingredients of the method are the consideration of some related derivatives and linear differential equations.

  19. Integrated Marketing Communications

    ERIC Educational Resources Information Center

    Black, Jim

    2004-01-01

    Integration has become a cliche in enrollment management and student services circles. The term is used to describe everything from integrated marketing to seamless services. Often, it defines organizational structures, processes, student information systems, and even communities. In Robert Sevier's article in this issue of "College and…

  20. Linear integrated circuits

    NASA Astrophysics Data System (ADS)

    Young, T.

    This book is intended to be used as a textbook in a one-semester course at a variety of levels. Because of self-study features incorporated, it may also be used by practicing electronic engineers as a formal and thorough introduction to the subject. The distinction between linear and digital integrated circuits is discussed, taking into account digital and linear signal characteristics, linear and digital integrated circuit characteristics, the definitions for linear and digital circuits, applications of digital and linear integrated circuits, aspects of fabrication, packaging, and classification and numbering. Operational amplifiers are considered along with linear integrated circuit (LIC) power requirements and power supplies, voltage and current regulators, linear amplifiers, linear integrated circuit oscillators, wave-shaping circuits, active filters, DA and AD converters, demodulators, comparators, instrument amplifiers, current difference amplifiers, analog circuits and devices, and aspects of troubleshooting.

  1. Retroviral integration: Site matters

    PubMed Central

    Demeulemeester, Jonas; De Rijck, Jan

    2015-01-01

    Here, we review genomic target site selection during retroviral integration as a multistep process in which specific biases are introduced at each level. The first asymmetries are introduced when the virus takes a specific route into the nucleus. Next, by co‐opting distinct host cofactors, the integration machinery is guided to particular chromatin contexts. As the viral integrase captures a local target nucleosome, specific contacts introduce fine‐grained biases in the integration site distribution. In vivo, the established population of proviruses is subject to both positive and negative selection, thereby continuously reshaping the integration site distribution. By affecting stochastic proviral expression as well as the mutagenic potential of the virus, integration site choice may be an inherent part of the evolutionary strategies used by different retroviruses to maximise reproductive success. PMID:26293289

  2. Integrated terahertz optoelectronics

    NASA Astrophysics Data System (ADS)

    Liang, Guozhen; Wang, Qi Jie

    2016-11-01

    Currently, terahertz (THz) optical systems are based on bulky free-space optics. This is due to the lack of a common platform onto which different THz components, e.g., source, waveguide, modulator and detector, can be monolithically integrated. With the development of THz quantum cascade laser (QCL), it has been realized that the QCL chip may be such a platform for integrated THz photonics. Here, we report our recent works where the THz QCL is integrated with passive or optoelectronic components. They are: 1) integrated graphene modulator with THz QCL achieving 100% modulation depth and fast speed; 2) phase-locked THz QCL with integrated plasmonic waveguide and subwavelength antennas realizing dynamically widely tunable polarizations.

  3. Integrated assessment briefs

    SciTech Connect

    1995-04-01

    Integrated assessment can be used to evaluate and clarify resource management policy options and outcomes for decision makers. The defining characteristics of integrated assessment are (1) focus on providing information and analysis that can be understood and used by decision makers rather than for merely advancing understanding and (2) its multidisciplinary approach, using methods, styles of study, and considerations from a broader variety of technical areas than would typically characterize studies produced from a single disciplinary standpoint. Integrated assessment may combine scientific, social, economic, health, and environmental data and models. Integrated assessment requires bridging the gap between science and policy considerations. Because not everything can be valued using a single metric, such as a dollar value, the integrated assessment process also involves evaluating trade-offs among dissimilar attributes. Scientists at Oak Ridge National Laboratory (ORNL) recognized the importance and value of multidisciplinary approaches to solving environmental problems early on and have pioneered the development of tools and methods for integrated assessment over the past three decades. Major examples of ORNL`s experience in the development of its capabilities for integrated assessment are given.

  4. GMRES and integral operators

    SciTech Connect

    Kelley, C.T.; Xue, Z.Q.

    1994-12-31

    Many discretizations of integral equations and compact fixed point problems are collectively compact and strongly convergent in spaces of continuous functions. These properties not only lead to stable and convergent approximations but also can be used in the construction of fast multilevel algorithms. Recently the GMRES algorithm has become a standard coarse mesh solver. The purpose of this paper is to show how the special properties of integral operators and their approximations are reflected in the performance of the GMRES iteration and how these properties can be used to strengthen the norm in which convergence takes place. The authors illustrate these ideas with composite Gauss rules for integral equations on the unit interval.

  5. On Quantum Integrable Systems

    SciTech Connect

    Danilov, Viatcheslav; Nagaitsev, Sergei; /Fermilab

    2011-11-01

    Many quantum integrable systems are obtained using an accelerator physics technique known as Ermakov (or normalized variables) transformation. This technique was used to create classical nonlinear integrable lattices for accelerators and nonlinear integrable plasma traps. Now, all classical results are carried over to a nonrelativistic quantum case. In this paper we have described an extension of the Ermakov-like transformation to the Schroedinger and Pauli equations. It is shown that these newly found transformations create a vast variety of time dependent quantum equations that can be solved in analytic functions, or, at least, can be reduced to time-independent ones.

  6. Space Station design integration

    NASA Technical Reports Server (NTRS)

    Carlisle, Richard F.

    1988-01-01

    This paper discusses the top Program level design integration process which involves the integration of a US Space Station manned base that consists of both US and international Elements. It explains the form and function of the Program Requirements Review (PRR), which certifies that the program is ready for preliminary design, the Program Design Review (PDR), which certifies the program is ready to start the detail design, and the Critical Design Review (CDR), which certifies that the program is completing a design that meets the Program objectives. The paper also discusses experience, status to date, and plans for continued system integration through manufacturing, testing and final verification of the Space Station system performance.

  7. The Integration Paradox

    PubMed Central

    Verkuyten, Maykel

    2016-01-01

    The integration paradox refers to the phenomenon of the more highly educated and structurally integrated immigrants turning away from the host society, rather than becoming more oriented toward it. This article provides an overview of the empirical evidence documenting this paradox in the Netherlands. In addition, the theoretical arguments and the available findings about the social psychological processes involved in this paradox are considered. The existing evidence for the integration paradox and what might explain it form the basis for making suggestion for future theoretical work and empirical research, and for discussing possible policy implications. PMID:27152028

  8. Vehicle/engine integration

    NASA Astrophysics Data System (ADS)

    Cooper, L. P.; Vinopal, T. J.; Florence, D. E.; Michel, R. W.; Brown, J. R.; Bergeron, R. P.; Weldon, V. A.

    1984-04-01

    VEHICLE/ENGINE Integration Issues are explored for orbit transfer vehicles (OTV's). The impact of space basing and aeroassist on VEHICLE/ENGINE integration is discussed. The AOTV structure and thermal protection subsystem weights were scaled as the vehicle length and surface was changed. It is concluded that for increased allowable payload lengths in a ground-based system, lower length-to-diameter (L/D) is as important as higher mixture ration (MR) in the range of mid L/D ATOV's. Scenario validity, geometry constraints, throttle levels, reliability, and servicing are discussed in the context of engine design and engine/vehicle integration.

  9. PEV Integration with Renewables (Prese