Posts Tagged “mtDNA”

Mitochondria contain their own DNA  which is about 17,000 bp. Mutation in mtDNA can lead to a series of disorders known as  mitochondrial disorders which will be very vivid in organs requiring high energy supply as brain, heart, eye & skeletal muscles. Owing to its oxidative function, mitochondria are having a high rate of mutations estimated to be 10 times that of nuclear DNA . However, mitochondrial disorders  result also from mutations in nuclear DNA in the  regions coding for mitochondrial components . For individuals having mitochondrial disorders resulting from mtDNA mutations , they have a mixture of mutated  mtDNA & normal mtDNA  which is a pattern of distribution known as mitochondrial DNA heteroplasmy. The proportion as well as the distribution of defective mtDNA influence the  location , onset as well as severity of diseases.



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                     Conventional treatment of mitochondrial disorders is mainly supportive where patients are treated with co-enzyme Q10, which is a cofactor required for electron transfer from complexes I & II to complex III. However Gene Therapy & Modern Targetting Systems stepped in offering a radical & permenant cure for mitochondrial disorders. One of  most promising strategies of Gene Therapy is allotropic expression which involves the  engineering of normal genes then their introduction to nucleus. This method showed success in a mitochondrial disorder characterized by respiratory deficient phenotypes caused by a mutant MATP8 gene , where the engineered ATP gene has succeeded in production of ATPase 8 protein.

Modern targetting systems have developed offering a unique solution to mitochondrial disorders & overcoming the dilemma of heteroplasmy as well. Cell membarne Crossing Oligopolymers (CMCO’s) are molecules  that are capable of penetrating cell membrane & selectively bind to mutated mtDNA inhibiting its replication. This technique has been successful in handling Oxidative Phosphorylation deficiency (OXPHOS deficiency).

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Reconstruction of a NeanderthaI child from GibraltarTwo years ago, the project of sequencing the Neanderthal genome started. They (Max Planck Institute & 454 Life sequencing) promised to end by this year. Well, they kept their promise. Frankly, some mitochondrial DNA sequences (mtDNA) have been published but contamination was the major defect in those published sequences. They collected more than 60 bone specimens from museums (We’re talking about 38,000-year-old bone); they repeated the sequencing for 35 times in the same clean room of extraction to avoid contamination with human DNA.


From the total 13 protein-encoding genes of the sequenced mtDNA, they identified only one with amino acids difference than the human sapien version. It is cytochrome c oxidase subunit 2 (COX2 – part of the respiratory chain), but even this difference has no significant effect on the functional domain of COX2. They hope to answer this questions in a few months: Why Neanderthals died out & human didn’t?!

We already know that Neanderthals & humans share 99.5% of the sequence, but answering questions about having a common ancestor & extinction through absorption (bred with humans) needs lots & lots of researches, collecting & sequencing samples at different time intervals to come with hypotheses. The mtDNA is not enough as Trinkaus (an expert on Neanderthal biology and human evolution) said: “The genome sequence data may tell us something about the selection of a couple of proteins, but it tells us nothing about language or social behavior.”

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Reconstruction of a Neanderthal child from Gibraltar:
First complete Neanderthal genome sequenced:

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