{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T05:44:36Z","timestamp":1772171076436,"version":"3.50.1"},"reference-count":65,"publisher":"Public Library of Science (PLoS)","issue":"11","license":[{"start":{"date-parts":[[2009,11,20]],"date-time":"2009-11-20T00:00:00Z","timestamp":1258675200000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ploscompbiol.org"],"crossmark-restriction":false},"short-container-title":["PLoS Comput Biol"],"DOI":"10.1371\/journal.pcbi.1000572","type":"journal-article","created":{"date-parts":[[2009,11,19]],"date-time":"2009-11-19T17:46:53Z","timestamp":1258652813000},"page":"e1000572","update-policy":"https:\/\/doi.org\/10.1371\/journal.pcbi.corrections_policy","source":"Crossref","is-referenced-by-count":33,"title":["Stochastic Drift in Mitochondrial DNA Point Mutations: A Novel Perspective Ex Silico"],"prefix":"10.1371","volume":"5","author":[{"given":"Suresh Kumar","family":"Poovathingal","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan","family":"Gruber","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Barry","family":"Halliwell","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudiyanto","family":"Gunawan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2009,11,20]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"44784","DOI":"10.1074\/jbc.M207217200","article-title":"Topology of superoxide production from different sites in the mitochondrial electron transport chain.","volume":"277","author":"J St-Pierre","year":"2002","journal-title":"J Biol Chem"},{"key":"ref2","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0014-5793(91)80347-6","article-title":"DNA damage by oxygen-derived species. Its mechanism and measurement in mammalian systems.","volume":"281(1\u20132)","author":"B Halliwell","year":"1991","journal-title":"FEBS lett"},{"key":"ref3","doi-asserted-by":"crossref","first-page":"839","DOI":"10.1093\/ajcn\/25.8.839","article-title":"Free radical theory of aging: dietary implication.","volume":"25","author":"D Harman","year":"1972","journal-title":"Am J Clin Nutr"},{"key":"ref4","doi-asserted-by":"crossref","first-page":"6554","DOI":"10.2741\/3174","article-title":"The mitochondrial free radical theory of ageing - Where do we stand?","volume":"13","author":"J Gruber","year":"2008","journal-title":"Front Biosci"},{"key":"ref5","doi-asserted-by":"crossref","first-page":"1284","DOI":"10.1080\/10715760600913168","article-title":"Mitochondrial DNA damage and the aging process: facts and imaginations.","volume":"40(12)","author":"RJ Wiesner","year":"2006","journal-title":"Free Rad Res"},{"key":"ref6","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1126\/science.1106653","article-title":"Extension of murine life span by overexpression of catalase targeted to mitochondria.","volume":"308","author":"SE Schriner","year":"2005","journal-title":"Science"},{"key":"ref7","doi-asserted-by":"crossref","first-page":"392","DOI":"10.1038\/ng.95","article-title":"DNA deletions and clonal mutations drive premature aging in mitochondrial mutator mice.","volume":"40","author":"M Vermulst","year":"2008","journal-title":"Nat Genet"},{"key":"ref8","doi-asserted-by":"crossref","first-page":"481","DOI":"10.1126\/science.1112125","article-title":"Mitochondrial DNA mutations, Oxidative stress, and Apoptosis in mammalian aging.","volume":"309","author":"GC Kujoth","year":"2005","journal-title":"Science"},{"key":"ref9","doi-asserted-by":"crossref","first-page":"417","DOI":"10.1038\/nature02517","article-title":"Premature ageing in mice expressing defective mitochondrial DNA polymerase.","volume":"429","author":"A Trifunovic","year":"2004","journal-title":"Nature"},{"key":"ref10","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/S0027-5107(99)00007-X","article-title":"Endogenous oxidative damage of mtDNA.","volume":"424","author":"KB Beckman","year":"1999","journal-title":"Mutat Res"},{"key":"ref11","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1080\/10715760290019246","article-title":"Inter-laboratory validation of procedures for measuring 8-oxo-7,8-dihydroguanine\/8-oxo-7,8-dihydro-2\u2032-deoxyguanosine in DNA.","volume":"36","year":"2002","journal-title":"Free Radic Res"},{"key":"ref12","doi-asserted-by":"crossref","first-page":"540","DOI":"10.1038\/ng1988","article-title":"Mitochondrial point mutations do not limit the natural lifespan of mice.","volume":"39(4)","author":"M Vermulst","year":"2007","journal-title":"Nat Genet"},{"key":"ref13","doi-asserted-by":"crossref","first-page":"10469","DOI":"10.1073\/pnas.171202698","article-title":"Does oxidative damage to DNA increase with age?","volume":"98","author":"ML Hamilton","year":"2001","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref14","doi-asserted-by":"crossref","first-page":"18891","DOI":"10.1016\/S0021-9258(17)46710-X","article-title":"Mitochondrial DNA remains intact during Drosophila aging, but the levels of mitochondrial transcripts are significantly reduced.","volume":"268","author":"M Calleja","year":"1993","journal-title":"J Biol Chem"},{"key":"ref15","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1038\/nmeth751","article-title":"Quantification of random genomic mutations.","volume":"2","author":"JH Bielas","year":"2005","journal-title":"Nat Methods"},{"key":"ref16","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1016\/S0168-9525(98)01659-X","article-title":"It&apos;s a noisy business! Genetic regulation at the nanomolar scale.","volume":"15","author":"HH McAdams","year":"1999","journal-title":"Trends Genet"},{"key":"ref17","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1038\/ng1769","article-title":"High levels of mitochondrial DNA deletions in substantia nigra neurons in aging and Parkinson disease.","volume":"38","author":"A Bender","year":"2006","journal-title":"Nat Genet"},{"key":"ref18","doi-asserted-by":"crossref","first-page":"322","DOI":"10.1096\/fj.00-0320com","article-title":"Mitochondrial DNA deletion mutations colocalize with segmental electron transport system abnormalities, muscle fiber atrophy, fiber splitting, and oxidative damage in sarcopenia.","volume":"15","author":"J Wanagat","year":"2001","journal-title":"FASEB J"},{"key":"ref19","doi-asserted-by":"crossref","first-page":"808","DOI":"10.1038\/nature01135","article-title":"Stochastic and genetic factors influence tissue-specific decline in ageing C. elegans.","volume":"419","author":"LA Herndon","year":"2002","journal-title":"Nature"},{"key":"ref20","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-662-05389-8","article-title":"Handbook of Stochastic Methods: for Physics, Chemistry and the Natural Sciences (Springer Series in Synergetics).","author":"CW Gardiner","year":"2004"},{"key":"ref21","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1016\/0006-291X(92)90517-O","article-title":"Counting target molecules by exponential polymerase chain reaction: copy number of mitochondrial DNA in rat tissue.","volume":"183(2)","author":"RJ Wiesner","year":"1992","journal-title":"Biochem Bioph Res Co"},{"key":"ref22","doi-asserted-by":"crossref","first-page":"R283","DOI":"10.1093\/hmg\/ddi270","article-title":"Emerging functions of mammalian mitochondrial fusion and fission.","volume":"14 Spec No. 2","author":"H Chen","year":"2005","journal-title":"Hum Mol Genet"},{"key":"ref23","doi-asserted-by":"crossref","first-page":"1158","DOI":"10.1086\/302311","article-title":"Relaxed replication of mtDNA: A model with implications for the expression of disease.","volume":"64","author":"PF Chinnery","year":"1999","journal-title":"Am J Hum Genet"},{"key":"ref24","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1146\/annurev.genet.40.110405.090613","article-title":"Mitochondrial retrograde signaling.","volume":"40","author":"Z Liu","year":"2006","journal-title":"Annu Rev Genet"},{"key":"ref25","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1086\/318801","article-title":"Random Intracellular Drift Explains the Clonal Expansion of Mitochondrial DNA Mutations with Age.","volume":"68","author":"JL Elson","year":"2001","journal-title":"Am J Hum Genet"},{"key":"ref26","doi-asserted-by":"crossref","first-page":"693","DOI":"10.1016\/0092-8674(82)90049-6","article-title":"Replication of animal mitochondrial DNA.","volume":"28","author":"DA Clayton","year":"1982","journal-title":"Cell"},{"key":"ref27","article-title":"Applied Statistics and Probability for Engineers.","author":"DC Montgomery","year":"2006"},{"key":"ref28","doi-asserted-by":"crossref","first-page":"18251","DOI":"10.1016\/S0021-9258(19)36949-2","article-title":"DNA Replication Fidelity.","volume":"267(26)","author":"TA Kunkel","year":"1992","journal-title":"J Biol Chem"},{"key":"ref29","doi-asserted-by":"crossref","first-page":"404","DOI":"10.1016\/0378-4371(92)90283-V","article-title":"A rigorous derivation of the chemical master equation.","volume":"188","author":"DT Gillespie","year":"1992","journal-title":"Physica A"},{"key":"ref30","article-title":"Markov Processes: An Introduction for Physical Scientists: Academic Press.","author":"DT Gillespie","year":"1991"},{"key":"ref31","doi-asserted-by":"crossref","first-page":"2340","DOI":"10.1021\/j100540a008","article-title":"Exact Stochastic Simulation of Coupled Chemical Reactions.","volume":"81","author":"DT Gillespie","year":"1977","journal-title":"J Phys Chem"},{"key":"ref32","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1017\/S0967199400001003","article-title":"Quantification of mtDNA in single oocytes, polar bodies and subcellular components by real-time rapid cycle fluorescence monitored PCR.","volume":"8","author":"N Steuerwald","year":"2000","journal-title":"Zygote"},{"key":"ref33","doi-asserted-by":"crossref","DOI":"10.1002\/9780470720226","article-title":"Embryogenesis in mammals (Ciba Foundation symposium; 40): Elsevier.","author":"K Elliott","year":"1976"},{"key":"ref34","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/0012-1606(87)90395-2","article-title":"Amounts of mitochondrial DNA and abundance of some mitochondrial gene transcripts in early mouse embryos.","volume":"123","author":"L Piko","year":"1987","journal-title":"Dev Biol"},{"key":"ref35","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1146\/annurev.ge.29.120195.001055","article-title":"Molecular genetic aspects of human mitochondrial disorders.","volume":"29","author":"NG Larsson","year":"1995","journal-title":"Annu Rev Genet"},{"key":"ref36","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1038\/ng0398-199","article-title":"An essential guide to mtDNA maintenance.","volume":"18","author":"DM Turnbull","year":"1998","journal-title":"Nat Genet"},{"key":"ref37","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/ng0398-231","article-title":"Mitochondrial transcription factor A is necessary for mtDNA maintenance and embryogenesis in mice.","volume":"18","author":"NG Larsson","year":"1998","journal-title":"Nat Genet"},{"key":"ref38","doi-asserted-by":"crossref","first-page":"199","DOI":"10.1016\/S0168-9525(01)02238-7","article-title":"What regulates mitochondrial DNA copy number in animal cells?","volume":"17(4)","author":"CT Moraes","year":"2001","journal-title":"Trends Genet"},{"key":"ref39","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/0002-9149(70)90575-8","article-title":"Developmental Landmarks in Cardiac Morphogenesis: Comparative Chronology.","volume":"25","author":"NJ Sissman","year":"1970","journal-title":"Am J Cardiol"},{"key":"ref40","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1242\/jcs.65.1.163","article-title":"Kinetics of in vitro ageing of mouse embryo fibroblasts.","volume":"65","author":"C Karatza","year":"1984","journal-title":"J Cell Sci"},{"key":"ref41","doi-asserted-by":"crossref","first-page":"3586","DOI":"10.1073\/pnas.062527199","article-title":"Embryonic stem cells and somatic cells differ in mutation frequency and type.","volume":"99(6)","author":"RB Cervantes","year":"2002","journal-title":"Proc Natl Acad Sci USA"},{"key":"ref42","doi-asserted-by":"crossref","first-page":"409","DOI":"10.1146\/annurev.biochem.66.1.409","article-title":"Mitochondrial DNA Maintenance in vertebrates.","volume":"66","author":"GS Shadel","year":"1997","journal-title":"Ann Rev Biochem"},{"key":"ref43","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1006\/geno.2000.6333","article-title":"Construction of Transgenic Mice with Tissue-Specific Acceleration of Mitochondrial DNA Mutagenesis.","volume":"69","author":"D Zhang","year":"2000","journal-title":"Genomics"},{"key":"ref44","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.cardiores.2005.08.014","article-title":"Autophagy in cardiac myocyte homeostasis, aging, and pathology.","volume":"68","author":"A Terman","year":"2005","journal-title":"Cardiovasc Res"},{"key":"ref45","doi-asserted-by":"crossref","first-page":"2203","DOI":"10.1152\/japplphysiol.00691.2002","article-title":"Measurement of mitochondrial DNA synthesis in vivo using a stable isotope-mass spectrometric technique.","volume":"94","author":"ML Collins","year":"2003","journal-title":"J Appl Physiol"},{"key":"ref46","doi-asserted-by":"crossref","first-page":"1552","DOI":"10.1016\/S0021-9258(18)91795-3","article-title":"Apparent turnover of mitochondrial Deoxyribonucleic acid and mitochondrial phospholipids in the tissues of the rat.","volume":"244(6)","author":"NJ Gross","year":"1969","journal-title":"J Biol Chem"},{"key":"ref47","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1126\/science.276.5309.60","article-title":"Liver regeneration.","volume":"276","author":"GK Michalopoulos","year":"1997","journal-title":"Science"},{"key":"ref48","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1016\/1357-4310(96)88743-0","article-title":"Hepatic cell division and tissue repair: a key to survival after liver injury.","volume":"2","author":"S Chanda","year":"1996","journal-title":"Mol Med Today"},{"key":"ref49","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1590\/S0100-879X1998000200012","article-title":"Mitochondrial DNA synthesis studied autoradiographically in various cell types in vivo.","volume":"31","author":"H Korr","year":"1998","journal-title":"Braz J Med Biol Res"},{"key":"ref50","doi-asserted-by":"crossref","first-page":"2425","DOI":"10.1016\/S0021-9258(18)62305-1","article-title":"The turnover of mitochondria in a variety of tissues of young adult and aged rats.","volume":"246","author":"RA Menzies","year":"1971","journal-title":"J Biol Chem"},{"key":"ref51","doi-asserted-by":"crossref","first-page":"920","DOI":"10.1111\/j.1474-9726.2008.00426.x","article-title":"Mitochondrial turnover in liver is fast in vivo and is accelerated by dietary restriction: application of a simple dynamic model.","volume":"7","author":"S Miwa","year":"2008","journal-title":"Aging Cell"},{"key":"ref52","doi-asserted-by":"crossref","first-page":"751","DOI":"10.1042\/bj20021594","article-title":"Mitochondrial threshold effects.","volume":"370","author":"R Rossigol","year":"2003","journal-title":"Biochem J"},{"key":"ref53","doi-asserted-by":"crossref","first-page":"883","DOI":"10.1083\/jcb.135.4.883","article-title":"In Situ Localization of Mitochondrial DNA Replication in Intact Mammalian Cells.","volume":"135","author":"AF Davis","year":"1996","journal-title":"J Cell Biol"},{"key":"ref54","first-page":"57","article-title":"Are we sure we know how to measure 8-oxo-7,8-dihydroguanine in DNA from human cells?","volume":"423(1)","author":"ARJ Cadet","year":"2004","journal-title":"Arch Biochem Biophys"},{"key":"ref55","doi-asserted-by":"crossref","first-page":"2129","DOI":"10.1093\/carcin\/23.12.2129","article-title":"Comparative analysis of baseline 8-oxo-7,8-dihydroguanine in mammalian cell DNA, by different methods in different laboratories: an approach to consensus.","volume":"23","year":"2002","journal-title":"Carcinogenesis"},{"key":"ref56","doi-asserted-by":"crossref","first-page":"99","DOI":"10.1016\/S0027-5107(98)00066-9","article-title":"Mutagenicity and repair of oxidative DNA damage: insights from studies using defined lesions.","volume":"400","author":"D Wang","year":"1998","journal-title":"Mutat Res"},{"key":"ref57","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1196\/annals.1338.023","article-title":"Oxidative damage in mitochondrial DNA is not extensive.","volume":"1042","author":"KS Lim","year":"2005","journal-title":"Ann N Y Acad Sci"},{"key":"ref58","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1042\/BJ20061131","article-title":"Oxidative stress and cancer: have we moved forward?","volume":"401","author":"B Halliwell","year":"2007","journal-title":"Biochem J"},{"key":"ref59","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1016\/0921-8734(93)90011-Q","article-title":"Mitochondrial mutations, cellular instability and ageing: modelling the population dynamics of mitochondria.","volume":"295","author":"A Kowald","year":"1993","journal-title":"Mutat Res"},{"key":"ref60","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1006\/jtbi.1999.1046","article-title":"Accumulation of Defective Mitochondria through delayed degradation of damaged organelles and its possible role in the ageing of post-mitotic and dividing cells.","volume":"202","author":"A Kowald","year":"2000","journal-title":"J Theor Biol"},{"key":"ref61","first-page":"163","article-title":"Changes in the weights of various organs and systems of young rats maintained on a low-protein diet.","volume":"5(2)","author":"M Limson","year":"1931","journal-title":"J Nutr"},{"key":"ref62","doi-asserted-by":"crossref","first-page":"17993","DOI":"10.1073\/pnas.0508886102","article-title":"Somatic mtDNA mutations cause aging phenotypes without affecting reactive oxygen species production.","volume":"102","author":"A Trifunovic","year":"2005","journal-title":"Proc Natl Acad Sci U S A"},{"key":"ref63","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1089\/rej.2004.7.171","article-title":"Mitochondrial mutations in mammalian aging: An over-hasty about-turn.","volume":"7(3)","author":"ADNJ Grey","year":"2004","journal-title":"Rejuv Res"},{"key":"ref64","doi-asserted-by":"crossref","first-page":"364","DOI":"10.1016\/0012-1606(87)90395-2","article-title":"Amounts of Mitochondrial DNA and Abundance of Some Mitochondrial Gene Transcripts in Early Mouse Embryos.","volume":"123","author":"L Piko","year":"1987","journal-title":"Dev Bio"},{"key":"ref65","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1096\/fasebj.11.11.9285481","article-title":"The Hill equation revisited: uses and misuses.","volume":"11","author":"JN Weiss","year":"1997","journal-title":"FASEB"}],"container-title":["PLoS Computational Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000572","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,10,14]],"date-time":"2021-10-14T09:06:07Z","timestamp":1634202367000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pcbi.1000572"}},"subtitle":[],"editor":[{"given":"Joel S.","family":"Bader","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2009,11,20]]},"references-count":65,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2009,11,20]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pcbi.1000572","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1260961.728060","asserted-by":"object"}]},"ISSN":["1553-7358"],"issn-type":[{"value":"1553-7358","type":"electronic"}],"subject":[],"published":{"date-parts":[[2009,11,20]]}}}