Stochastic drift in mitochondrial DNA point mutations: a novel perspective ex silico.

PLoS Computational Biology
Suresh Kumar PoovathingalRudiyanto Gunawan

Abstract

The mitochondrial free radical theory of aging (mFRTA) implicates Reactive Oxygen Species (ROS)-induced mutations of mitochondrial DNA (mtDNA) as a major cause of aging. However, fifty years after its inception, several of its premises are intensely debated. Much of this uncertainty is due to the large range of values in the reported experimental data, for example on oxidative damage and mutational burden in mtDNA. This is in part due to limitations with available measurement technologies. Here we show that sample preparations in some assays necessitating high dilution of DNA (single molecule level) may introduce significant statistical variability. Adding to this complexity is the intrinsically stochastic nature of cellular processes, which manifests in cells from the same tissue harboring varying mutation load. In conjunction, these random elements make the determination of the underlying mutation dynamics extremely challenging. Our in silico stochastic study reveals the effect of coupling the experimental variability and the intrinsic stochasticity of aging process in some of the reported experimental data. We also show that the stochastic nature of a de novo point mutation generated during embryonic development is a major c...Continue Reading

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Citations

Oct 1, 2013·Journal of Theoretical Biology·Erica J Graham, Frederick R Adler
Apr 5, 2011·Nucleic Acids Research·Jocelyn H WrightJean S Campbell
Dec 20, 2011·Nucleic Acids Research·Suresh Kumar PoovathingalRudiyanto Gunawan
Dec 15, 2010·Biogerontology·S SchafferB Halliwell
Aug 7, 2012·Biogerontology·Suresh Kumar PoovathingalRudiyanto Gunawan
May 23, 2015·PLoS Computational Biology·Zhi Yang TamRudiyanto Gunawan
Nov 16, 2016·American Journal of Human Genetics·Iain G Johnston, Nick S Jones
Apr 10, 2015·Nucleic Acids Research·Lakshmi Narayanan LakshmananRudiyanto Gunawan
Jun 30, 2019·Genetics·Juvid AryamanIain G Johnston
Aug 4, 2019·Scientific Reports·Alexander HübnerMark Stoneking
Sep 6, 2019·Biochemical Society Transactions·Iain G Johnston, Joerg P Burgstaller
Feb 12, 2019·Frontiers in Genetics·Juvid AryamanNick S Jones
Mar 6, 2021·IScience·Lakshmi Narayanan LakshmananRudiyanto Gunawan
Aug 1, 2019·Genetics·Juvid AryamanIain G Johnston

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Methods Mentioned

BETA
transgenic
PCR

Software Mentioned

CentOS Linux
mFRTA
G77
GNU
SSA

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