What is DNA?: MedlinePlus Genetics Nuclear DNA Tissues were stored at 80C and transported to Cambridge, UK on dry ice for analysis. Quantitative image analysis was performed using the Metamorph platform (Molecular Devices)25. Mitochondrial DNA:mtDNA encodes each and every tRNA and rRNA required by mitochondria. (CC BY-SA 3.0) via Commons Wikimedia, Lakna, a graduate in Molecular Biology & Biochemistry, is a Molecular Biologist and has a broad and keen interest in the discovery of nature related things, Difference Between Mitochondrial DNA and Nuclear DNA, What is the difference between Mitochondrial DNA and Nuclear DNA. Nuclear and mitochondrial DNA repair: Similar pathways? Nuclear DNA: nDNA consists of the cells genome, including the mitochondrial DNA. Mitochondrial DNA:mtDNA has a less contribution to the individuals fitness among the population. Studies in mice show that the mitochondrial transcription factor A (TFAM, mtTFA), which belongs to the high mobility group (HMG) protein family is critical for maintaining a stable mtDNA number (Ekstrand et al., 2004).In mouse embryos the number of mtDNA copies correlates with the . Cell-free DNA (cfDNA) is released into the bloodstream from cells in various physiological and pathological conditions. The MRS analysis revealed that mature BL/6NZB adults (40 weeks) had higher tissue lipid content despite their lower body weight (Fig. The number of mtDNA copies per cell depends on the number of mtDNA copies per mitochondria as well as the size and the number of mitochondria per cell. How are mitochondrial DNA and nuclear similar? Calculation of statistical weights of each quantitation at the spectrum level was performed according to the WSPP model. (XLSX 116 kb), Data compiling the transcripts differentially expressed in liver and heart between conplastic mouse strains. Mice were euthanized by cervical dislocation and the left ventricle apex was immediately dissected (12 weeks old, n=3 per genotype and 80 weeks old, n=2 per genotype). 3e, f). Mitochondrial DNA:mtDNA is maternally inherited. Throughout the 24h measurement period, oxygen consumption and carbon dioxide production rates were measured at 24-min intervals, with a 4min sample period and a 1min purge; simultaneous measurements were made in four metabolic chambers. Conversely, the opposite could also be true. But, some proteins, which are encoded by nuclear DNA are imported from the cytosol. Abstract. 4. Molecular Poltergeists: Mitochondrial DNA Copies This theory is called the endosymbiotic theory. Solved Mitochondrial DNA is/are A) similar to nuclear DNA - Chegg Data are given as meanss.e.m., non-parametric KruskalWalls test (not normal distribution), *P<0.05; **P<0.01; ***P<0.001; ****P<0.00001; NS, not significant. b, Heatmap and hierarchical clustering of enrichment (log10 BenjaminiHochberg (BH)-adjusted P values) of the functions defined by the ingenuity pathway analysis (IPA) in set of genes differentially expressed between conplastic mice in heart (H) (top) and liver (L) (bottom). Nuclear DNA damage signalling to mitochondria in ageing List of Genetic Diseases: Definitions, Types, & Examples. MedicineNet. Mitochondrial DNA: The rate of mutations in mtDNA is comparatively high. Nuclear vs. mitochondrial DNA - Understanding Science Nuclear DNA and Mitochondrial Damage of the Cooked Meat Carcinogen 2 Consistent with this, the proteomic analysis revealed liver content changes in glycolytic and -oxidization enzymes (Extended Data Fig. Mice were bled from a tail clip. F.S.-C. and C.T. Mitochondrial DNA (mtDNA) alterations are implicated in a broad range of human diseases and alterations of the mitochondrial genome are assumed to be a result of its high susceptibility to oxidative damage and its limited DNA repair compared to nuclear DNA (nDNA). Variants were called using the Torrent Variant Caller (TVC) version 5.0.7, applying a minimum allele frequency threshold of 0.001 and reducing the coverage to 10,000 in over-sampled locations (keeping default values for somatic mutations for the rest of parameters) and then filed into variant call format (VCF) reports. Significance was assessed by nonparametric MannWhitney U-test. Therefore, per cell, more than 1,000 copies of mtDNA can be found. Experiments were performed in an independent group of 12 mice per genotype. Nature 535, 561565 (2016). Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. The mtDNA is composed of a double-stranded, circular DNA molecule, which is arranged into a single chromosome. For more information on ageing parameters see Extended Data Fig. The DDR involves primarily DNA repair which can be combined with or replaced by cell cycle control mechanisms, tolerance to DNA damage including replication bypass, and eventually to triggering cellular death mechanisms: apoptosis, autophagy, and/or mitotic catastrophe [ ]. Properties of average score distributions of SEQUEST: the probability ratio method. U.S. National Library of Medicine, 01 Jan. 1970. c, Activity profiles (BL/6NZB, BL/6C57, and NZBNZB separated by sex, 10-week-old mice, n=10 per group). 5. Characterization of DNA repair mechanisms has generally focused on these processes in nDNA but increasing interest and research . Nuclear DNA (nDNA) is composed of several linear chromosomes, which encodes almost all the proteins required by the cell. Mitochondria consists of multiple mtDNA molecules. Feature. Mice aged ~2 years old were scored for a variety of ageing markers (reduced hair density, greying hair, kyphosis, body weight reduction and development of systemic neoplasias) as previously described10. h, Representative heart TEM images illustrating differences in mitochondria and lipid droplets between 20-week-old conplastic mice (n=3 per genotype). Genome Res. Each peptide was assigned only to the best protein proposed by the Proteome Discoverer algorithm. 5b). performed the telomere analysis. Nuclear DNA: The nDNA is used to in paternity testing. Mitochondrial DNA:mtDNA is not enclosed by the nuclear envelope. a, Two-year-old mice were scored for conspicuous signs of the indicated ageing parameters (0 (none) to 3 (high))10. b, Representative image of 2-year-old animals. On the other hand, inheritance of diseases is also characteristic to the parents. Studies in conplastic animals7,8,9 allow comparison of individuals with the same nuclear genome but different mtDNA variants, and have provided both supporting and refuting evidence that mtDNA variation influences organismal physiology. Telomere length was measured in tail skin samples by quantitative fluorescence in situ hybridization (Q-FISH). the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Correspondence to The first diurnal phase (12h) was considered part of the acclimatization period and was eliminated from the final result. Organelle DNAs. Molecular Cell Biology. When indicated, mice were treated with 1% NAC in drinking water for 8 weeks before MitoB injection. A test using modular kinetic analysis of coupling in mitochondria from cybrid cell lines. An exponential line broadening (3Hz for proton) was applied before Fourier transformation. mtDNA is the mitochondrial DNA that differs from nuclear DNA in a number of characteristics (Table 1). f, Tumour incidence in animals dying from natural causes (n=14 for BL/6NZB, n=20 for BL/6C57; **P<0.01, Fishers exact test). Total RNA was extracted with TRIzol reagent and then purified on RNeasy spin columns (Qiagen). Raw reads and TMM-normalized batch corrected counts have been deposited in GEO with the accession number GSE56933. Mitochondrial DNA (mtDNA) is a double-stranded, circular DNA found inside the mitochondria. However, BL/6NZB mice of all ages showed a slightly but consistently lower level of CI:CIII superassembly (Extended Data Fig. Nature 497, 451457 (2013), Kelso, G. F. et al. 28 Mar. i, Quantification of lipid content by 1H MRS in skeletal muscle (soleus) of 80-week-old animals (n=4 per genotype). 22, 654667 (2008), Robinson, M. D., McCarthy, D. J. This difference correlated with a lower capacity of BL/6C57 mice to regulate insulin levels (Fig. False discovery rate and overfitting were avoided by using a leave-one-out cross-validation, performed with the calibration data set, to determine the number of latent variables for each fold and to construct a model. In parallel with the age-related decline in respiration in BL/6C57 mice (Fig. CAS Proteomics 15, 17401760 (2016). Biochem. (XLSX 234 kb), Compilation of the iTRAQ proteomic analysis. Four days after birth, respiration and ATP synthesis were lower in liver mitochondria from BL/6NZB mice. In humans, mitochondrial DNA spans about 16,500 DNA building blocks (base pairs), representing a small fraction of the total DNA in cells. Breaking Down Cell-Free DNA Fragmentation: A Markov Model Approach What is Mitochondrial DNA Definition, Structure and Composition, Function 2. mitochondrial repair and recombination activities. It is composed of around 0.25% of the genetic makeup of the cell. Chem. Thus non-pathological mitochondrial DNA variants have a broad effect on metabolism, with the differences more pronounced later in life. 4e). 1f and Extended Data Fig. 35, 6569 (2003), Yu, X. et al. The conplastic strains showed differences in critical components of the apparatus involved in mitochondrial dynamics (Fig. Reference:1. Many studies suggest that mtDNA variants may be associated with ageing or diseases2,3,4, although mechanistic evidence at the molecular level is lacking5,6. Mice found dead at each daily inspection were considered as censored deaths, and were necropsied to tumour inspection. and JavaScript. Human somatic cells are diploid, containing two copies of nDNA, which are called homologous chromosomes. Data from the Next generation sequencing of mtDNA from both conplastic strains at three different ages. The mtDNAs of C57BL/6 and NZB/OlaHsd mice differ by 12 missense mutations, 4 transfer RNA (tRNA) mutations, 8 ribosomal RNA (rRNA) mutations, and 10 non-coding-region mutations (Extended Data Fig. Nuclear DNA: nDNA contains non-coding regions of DNA like introns and untranslated regions. Liver mtDNA sequencing revealed no age-related increase in mtDNA mutations in either mtDNA backgrounds (Extended Data Table 2, Supplementary Data 1). In liver, the major mitochondria-located redox regulators Glrx2, Glrx5 and Txnrd2 were increased in young and old BL/6NZB mice, whereas cytosolic gamma-glutamyltranspeptidase 1 (involved in glutathione pool maintenance) and four mitochondrial redox regulators (Prdx3, Txnrd2, Sod2 and Nnt) were decreased in young BL/6NZB mice but then strongly increased on ageing (Fig. Slides from liver necropsies were digitalized and analysed with NDP.view2 viewing (Hamamatsu). 2d. What is the difference between Mitochondrial DNA and Nuclear DNA. 3a); equalized mtDNA copy number (Fig. Male BL/6NZB and BL/6C57 mice (80 weeks old (n=45), 20 weeks old (n=68)) weighing 3050g each were housed in groups of 4 with unrestricted access to food and water. The mtDNA is more susceptible to mutations when compared to nuclear DNA. Cell 153, 11941217 (2013), Soga, T. et al. 4f) and had a decreased mitochondrial area (Fig. Top: complex I, (Ndufa9); middle: complex III (core-2); bottom: complex IV (Cox5b) and Tom20. Nuclear DNA is coiled around histones, but mitochondrial DNA, together with associated proteins, is located in mitochondrial pseudocompartments called . These changes were due to a steady decline in BL/6C57 respiration, with BL/6NZB respiration remaining constant between days 20 and 300 (Fig. Based on this, we selected only those metabolites that appear in at least 50% of the repeated analysis. Selective targeting of a redox-active ubiquinone to mitochondria within cells: antioxidant and antiapoptotic properties. The nuclear DNA is conventionally used to assess the diversity and relatedness among different species, but variations at the DNA genome level has also been used to study the relationship among different organisms. The DAPI images were signal-intensity thresholded and segmented using ImageJ. e, f, Heat maps and hierarchical clustering of enrichment (Zq differences between indicated genotypes and/or ages) of the proteins quantified by iTRAQ involved in ROS metabolism in either liver (e) or heart (f). 2nd edition. mtDNA consists of 37 genes that are essential for regular mitochondrial functions. Nuclear mitochondrial DNA segment - Wikipedia We report that (1) mitochondrial principal component analysis (PCA) captures ethnic variation to a similar or slightly greater degree than nuclear PCA in Blacks and Hispanics, (2) nuclear and mitochondrial DNA classify self-reported ethnicity to a high degree but with a similar level of error, and 3) mitochondrial principal components can be . Nature Genet. d, Representative haematoxylin and eosin stained paraffin sections of liver adenoma, carcinoma, histiocytic sarcoma and hemangiosarcoma. A moderated t-test, also implemented in the LIMMA package, was used to calculate log fold-differences between male BL/6NZB and BL/6C57 mice for liver and plasma samples separately, together with raw and BenjaminiHochberg adjusted P values. It encodes for the majority of the genome in eukaryotes, with mitochondrial DNA and plastid DNA coding for the rest. Get the most important science stories of the day, free in your inbox. 2a, b), with marginal differences in activity observed in metabolic chambers (Extended Data Fig. 4c, d). Levels of serum cholesterol (ChoT), low-density lipoprotein (LDL), and high-density lipoprotein (HDL) were determined by biochemical analysis of submandibular blood samples. Similarities between the DNA of mitochondria and chloroplasts and the DNA of bacteria are an important line of evidence supporting the endosymbiont theory, which suggests that mitochondria and chloroplasts originated as free-living prokaryotic cells. Mitochondrial DNA: mtDNA is double-stranded and circular. Nuclear DNA:nDNA is tightly packed with histone proteins. 3b), CI was less abundant in liver of young BL/6NZB mice (Extended Data Fig. Long-range PCRs were carried out using Takara Taq DNA Polymerase (Clontech). Which of the following is defined as "heat content"? Nature Rev. 38, 12611268 (2006), Lapuente-Brun, E. et al. d, Area under the curve analysis of the activities shown in c, providing estimated activity intensities of the different strains. These genes are encoded for almost all the characters exhibited by the organism. Each data represent mean of 4 technical replicates. The CNIC is supported by the MEyC and the Pro-CNIC Foundation and is a SO-Center of Excellence (SEV-2015-0505). Conplastic strains were obtained by backcrossing females (mitochondrial donors) with males of the parental recipient strain over 20 generations to create a new line harbouring the nuclear genome of one strain and the mtDNA of the other. 8, 17921796 (2009), Garca-Marqus, F. et al. 2e). Mitochondrial DNA:mtDNA is arranged into a single chromosome. Heat maps are accompanied by MSEA assessment of significant (red) or nonsignificant differences (FDR). 276, 45884596 (2001), Tachibana, M. et al. 1a, b, f) were done in the same group of animals. Biochim. Nuclear and mitochondrial DNA are thought to be of separate evolutionary origin, with the mtDNA being derived from the circular genomes of bacteria engulfed by the early ancestors of today's eukaryotic cells. of mitochondrial DNA (mtDNA) are remarkably similar. Internet Explorer). Nuclear-mitochondrial DNA segments resemble paternally inherited This may reflect the accelerated deterioration of older BL/6C57 mice, with replacement of muscle mass by fat. In yeast, inheritance of mitochondria is biparental. 1g). After 9 months, BL/6NZB mice gained less weight (Fig. Bioinformatics 26, 139140 (2010), Subramanian, A. et al. b, Organ-weight to body-weight ratios separated by sex (n=10 per group, ANOVA test). 1ce). Ultra-thin sections (60nm) were then mounted on copper grids and stained with lead citrate. Based on key structural and functional properties, these differences affect how they operate within eukaryotic organisms. c, d, Detected proteases involved in the mitochondrial UPR and mitochondrial dynamics. A.G.-G., M.L.B.-M. and E.R. Serum biochemistry was conducted in a Dimension RxL Max automated analyser. E.A. Unless specified, statistical analyses and graphics were produced with GraphPad Prism 6 software. For example, human nDNA is arranged into 46 chromosomes. Respiratory exchange rate (RER, or respiratory quotient, RQ), a measure of metabolic substrate choice, was calculated as the ratio between CO2 production and O2 consumption. 3a. We developed a conplastic mouse strain (Extended Data Fig. Extended Data Figure 7 Lipid metabolism phenotype. Because of their relatively small size and ease of purification, mtDNAs have been well character-ized in a number of species, and for some of them the 1b was generated with Geneious version 9.1.2, created by Biomatters. Nuclear DNA: Cystic fibrosis, sickle cell anemia, hemochromatosis and Huntingtons disease are the examples of genetic diseases caused by the mutations in nDNA. 2d and Extended Data Fig. The mice were fed a standard chow diet (5K67 LabDiet) or, when indicated, a high-fat diet (D12492 Open Source Diets). Genes with at least one count per million in at least three samples were considered for downstream analysis. Most DNA is located in the cell nucleus (where it is called nuclear DNA), but a small amount of DNA can also be found in the mitochondria (where it is called mitochondrial DNA or mtDNA). To avoid confusion, we call C57BL/6JOlaHsd mice C57BL/6 throughout the manuscript. 110, 130138 (2002), Baudouin, S. V. et al. http://www.bu.edu/jlab/wp-assets/ComBat/Download.html. Template preparation and Ion PI Chip loading were performed on the Ion Chef Instrument. Data were analysed with Metabolism v2.2 (Panlab). Phylomitogenomics reveals mitonuclear concordance in social wasps: The As shown in cultured cells14, high levels of mitochondrial ROS correlated with mtDNA copy number (Fig. BenjaminiHochberg adjusted P values are reported for differential gene expression and IPA functional analysis. Mice fed the chow diet were fasted for 6 or 16h with free access to water. The authors declare no competing financial interests. Peptides were eluted from the RP nano-column at a flow rate of ~200nlmin1 to an emitter nanospray needle for real-time ionization and peptide fragmentation in a Q-Exactive HF mass spectrometer (Thermo Fisher). 5 and Supplementary Data 3). If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate. Heart and liver protein extracts from 12- or 80-week-old BL/6C57 and BL/6NZB mice (n=3 per genotype and age) were reducted, alkylated with iodoacetamide and digested with trypsin and the resulting peptides were labelled with iTRAQ8-plex, according to the manufacturers instructions. Genes are expressed into proteins according to the universal genetic code through transcription and translation. *P<0.05, two-tailed t-test). The nDNA contains huge variations of the traits they exhibit due to the presence of various alleles per a particular gene. Investigators were not blinded to the group allocation when assessing the outcome. However, mitochondrial ROS production was inverted in animals above 30 weeks of age, with BL/6NZB liver mitochondria from middle-aged mice producing similar levels of ROS to young animals, whereas BL/6C57 mitochondria showed a sharp, age-related increase in ROS (Fig. The nDNA is less prone to mutations. a, Relative amount of H2O2NAC. Rates of Nucleotide Substitution in Drosophila Mitochondrial DNA and Centro Nacional de Investigaciones Cardiovasculares Carlos III, Madrid, 28029, Spain, Ana Latorre-Pellicer,Ana Victoria Lechuga-Vieco,Ftima Snchez-Cabo,Carlos Torroja,Rebeca Acn-Prez,Enrique Calvo,Esther Aix,Andrs Gonzlez-Guerra,Sara Cogliati,Jess Ruz-Cabello,Ignacio Flores,Jess Vzquez&Jos Antonio Enrquez, Grupo de Medicina Xenmica, CIBERER, Universidad de Santiago de Compostela, Santiago de Compostela, 15782, Spain, Ana Latorre-Pellicer,Raquel Cruz&ngel Carracedo, Departamento de Bioqumica y Biologa Molecular y Celular, Universidad de Zaragoza, Zaragoza, 50009, Spain, Raquel Moreno-Loshuertos,Acisclo Prez-Martos,Patricio Fernndez-Silva&Jos Antonio Enrquez, CIBERES, C/ Melchor Fernndez-Almagro 3, Madrid, 28029, Spain, Ana Victoria Lechuga-Vieco&Jess Ruz-Cabello, Medical Research Council Mitochondrial Biology Unit, Hills Road, Cambridge, CB2 0XY, UK, SAI de Biomedicina y Biomateriales & Phenotypic Unit, Instituto Aragons de Ciencias de la salud, Zaragoza, 50009, Spain, Mara Luisa Bernad-Miana&Eduardo Romanos, Fundacin Pblica Gallega Medicina Xenmica, SERGAS, Complexo Hospitalario Universitario de Santiago, Santiago de Compostela, 15706, Spain, Center of Excellence in Genomic Medicine Research, King Abdulaziz University, Jeddah, 21589, Saudi Arabia, Universidad Complutense de Madrid, Madrid, 28606, Spain, You can also search for this author in 7b, c). The C57BL/6JOlaHsd strain does not harbour the nicotinamide nucleotide transhydrogenase (NNT) spontaneous mutation that renders the encoded enzyme undetectable, and which is characteristic of the C57BL/6J strain provided by Jackson Laboratories. 2e, f and Supplementary Data 4). 1a). Samples of liver and plasma from 10-week-old mice (n=6 per genotype) were collected, frozen in liquid nitrogen and sent to Metabolon (Durham, NC, USA) for metabolomics analysis according to their proprietary methodology. We show that mtDNA haplotype profoundly influences mitochondrial proteostasis and reactive oxygen species generation, insulin signalling, obesity, and ageing parameters including telomere shortening and mitochondrial dysfunction, resulting in profound differences in health longevity between conplastic strains. 2017. See also Extended Data Table 1. c, Cluster dendrogram based on the expressed genome of the indicated mouse strain and the RNA-seq-derived expressed genome of conplastic animals. 1History 2Mechanism of NUMT insertion 3General characteristics of NUMT 4Consequences of de novo integration of NUMT inserts Morphological and molecular analysis of Mitochondrial DNA:mtDNA encodes for most of the proteins, which are required by mitochondria. The ligated DNA was purified using Agencourt AMPure XP Reagent. A) energy output B) heat loss C) entropy. Twelve 10-week-old males per genotype were killed by cervical decapitation, and liver (median lobe) and heart (left ventricle) tissues were dissected and immediately frozen in liquid nitrogen. c, Relative liver mitochondrial H2O2 generation (126 days old, n=2 per genotype; 210 days old, n=6 per genotype). Heart samples were fixed in 2.5% glutaraldehyde, 4% formaldehyde in 0.1M HEPES buffer for 45h. After buffer washes, samples were post-fixed for 1h at room temperature in a 1:1 solution of 1% osmium tetroxide and 3% aqueous potassium ferrocyanide. Dissecting the effects of mtDNA variations on complex traits using mouse conplastic strains. Proton chemical shifts were expressed relative to the water signal (4.7p.p.m.). J Mol Biol 80 (1):155-175. Heart transmission electron microscopy (TEM) revealed between-strain differences in mitochondrial aspect and dynamics, affecting density, morphology and cristae area (Fig. To calculate growth curves, mice were weighed at the starting age and every week/month thereafter for the period indicated in each experiment. Jos Antonio Enrquez and colleagues look into the effects of mitochondrial DNA sequence variation by using congenic mice strains that share the same nuclear genome, but have different mitochondrial DNA. Association between Chloroplast and Mitochondrial DNA sequences in Mol. The inheritance of nDNA is biparental. Understanding Science 101 What is science? Purple text denotes mitochondrial location (n=3 per genotype and age). Web. (XLSX 71 kb), This zipped file contains the original gel data for Extended Data Figure 5a. Cell 151, 333343 (2012), Ross, J. M. et al. 1a) with the C57BL/6 nuclear genome and the NZB/OlaHsd mtDNA, hereafter referred to as BL/6NZB. 1. A scientific approach to life: A science toolkit For Educators Prepare and plan Guide to US 101 Conceptual framework Both the nuclear ITS2 and mitochondrial CO1 genes were amplified with universal primers of 3 S (forward) and A28 (reverse) for ITS2 (Blair et al. Chronic treatment of mice with N-acetyl cysteine (NAC) reduced the BL/6NZB MitoP:MitoB ratio (Fig. Mitochondrial DNA-like sequences in the nucleus (NUMTs - PubMed and I.F. ISSN 0028-0836 (print). Wallace, D. C. Mitochondrial DNA variation in human radiation and disease. Briefly, 25nmol MitoB was injected into the tail vein between 8 a.m. and 10 a.m. After 6h, mice were euthanized by cervical dislocation and tissues were harvested and flash frozen in liquid nitrogen. Colour-coding in all heat maps represents the log fold difference between BL/6NZB and BL/6C57 mice (black, not detected; white, no change (log fc=1); red, trend for enrichment in BL/6NZB samples (log fc >1); yellow, trend for depletion in BL/6NZB samples (log fc <1). The original X matrix contains the metabolic variables, while the Y matrix contains the class variable for which values are chosen to be the class descriptor. Mitochondrial and Nuclear DNA Damage and Repair in Age-Related Macular Mitochondrial DNA: Lebers hereditary optic neuropathy, Kearns-Sayre syndrome and chronic progressive external ophthalmoplegia are the examples of the genetic diseases caused by the mutations of mtDNA. Nuclear DNA: nDNA is composed of 99.75% of the cells genetic makeup in animal cells. Extended Data Figure 5 Differentially regulated metabolites and metabolic pathways in liver and plasma. A single mitochondrion consists of dozens of mtDNA copies.

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