Mitochondrial DNA vs Nuclear DNA

Mitochondrial DNA vs Nuclear DNA – detailed comparison:

Mitochondrial DNA

Mitochondrial DNA (mtDNA) is the DNA located in mitochondria, which are cellular organelles within eukaryotic cells which transform chemical energy from food into adenosine triphosphate.

Each cell contains hundreds to thousands of mitochondria, that are located in the fluid which surrounds the cytoplasm (the nucleus). Along with plastids in plants, mitochondria are the only cytoplasmic organelles in the eukaryotic cell that transport genetic elements.

In humans, mtDNA spans approximately 16,500 DNA building blocks, representing a small fraction of the total DNA in cells. Human mtDNA was the 1st important part of the human genome to be sequenced.

Interestingly, the presence of totally separate mtDNA has led many researchers to think that mitochondria are separate bacteria that live inside the cells.

Paternal mitochondria are degraded by autophagy in C. elegans mechanism in mammals. However, mtDNA is only inherited maternally in most animals. Because mitochondrial DNA comes from the mother, it does not change very much, from generation to generation.

Hence, an individual’s mitochondrial DNA is most likely identical to that of her or his direct maternal ancestor many generations ago, and this interesting fact can be used to link individuals across decades.


Mitochondrial DNA is vital for numerous reasons. It has 37 genes. 24 of these genes are involved in the creation of ribosomal RNA and transfer RNA that help to turn amino acids into proteins.

The remainder 13 of its 37 genes are involved in the process known as oxidative phosphorylation. This is the metabolic pathway in which adenosine triphosphate is created as a result of the transfer of electrons from NADH or FADH2 to O2 by a series of electron transporters.

Moreover, mtDNA replication is important for maintaining mitochondrial DNA copy numbers to generate proper cellular energy, which is needed for growth and for functional cells.

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There is some evidence linking somatic mutations in mtDNA with some types of cancers, including colon, stomach, liver, kidney, and breast tumors. Also, these mutations might be linked with cancer of immune system cells (lymphoma) and cancer of blood-forming tissue (leukemia).

The types of disorders that are inherited through mutations of the mtDNA tend to involve disorders of nerve function, as neurons need significant amounts of energy to function correctly.

The best known of the mitochondrial disorders is Leber hereditary optic neuropathy, an inherited form of vision loss characterized by vision loss, especially in young males.


Human mtDNA has become a useful tool in forensic investigations. Its maternal inheritance and polymorphic nature are characteristics that have enabled investigators to identify war casualties, missing persons, and individuals involved in mass criminal cases and disasters.

Many cold cases (a crime that has not yet been fully solved) have been re-opened in hopes that mitochondrial DNA profiling of evidentiary material may identify new leads and new suspects or strengthen a case against an existing but weak suspect.

Additionally, it is thought that mitochondrial DNA is responsible for the explosion of studies in molecular phylogenetics (the branch of phylogeny, which analyzes genetic and hereditary molecular differences) and population genetics in the last decades.

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Nuclear DNA

Nuclear DNA (nDNA) encodes the main structure of proteins, consisting of the basic amino acid sequence. It is inherited from both parents.

Nuclear DNA is composed of a few linear chromosomes that encode almost all the proteins needed by the cell.

It resides only in the membrane-bound cell nucleus, whereas mtDNA molecules are found in the mitochondria that are scattered throughout the cell cytoplasm.

Another feature of nDNA is that it is regulated by RNA systems and proteins that control the rate of transcription into messenger RNA. Therefore, most of the cell products are adjusted according to the circumstances.

Interesting Facts

Harvard scientists and the FBI have succeeded in sequencing a degraded mitochondrial genome, and pieces of nDNA, from an Egyptian mummy’s head.

In 2018, the Moroccan culture ministry announced the discovery of the oldest nDNA from Africa in Morocco, adding new hints to a better understanding of human history.

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Mitochondrial DNA vs Nuclear DNA – Differences

Similar to the nuclear genome, the mitochondrial genome is built of double-stranded DNA, and it encodes genes. But, the mitochondrial genome differs from the nuclear genome in a few ways, including the following:

  • mitochondrial genes on both DNA strands are transcribed in a polycistronic manner: large mRNAs contain the instructions to build numerous proteins, that are encoded one after the next along the mitochondrial RNA. In contrast, nuclear genes are generally transcribed one at a time from their own mRNA;
  • nuclear genomes are inherited equally from both parents, whereas the mitochondrial mode of inheritance is strictly maternal. Hence, mitochondria-associated disease mutations are always inherited maternally;
  • some mitochondrial nucleotide bases exhibit functional overlap between 2 genes;
  • some mitochondrial coding sequences do not follow the universal codon usage rules when they are translated into proteins;
  • the mitochondrial genome contains few noncoding DNA sequences (whereas 93 percent of the nuclear genome is noncoding DNA, whereas about 3% of the mitochondrial genome is noncoding DNA);
  • the mitochondrial genome is not packaged and enveloped into chromatin (a complex of macromolecules found in cells, consisting of protein, DNA, and RNA);
  • mtDNA molecules are found in the mitochondria that are scattered throughout the cell cytoplasm whereas nDNA resides only in the membrane-bound cell nucleus;
  • 1 mitochondrion contains many copies of its mitochondrial genome. Furthermore, each cell contains numerous mitochondria. Hence, a given cell can contain a few thousand copies of its mitochondrial genome, however, only one copy of its nuclear genome;
  • the small mitochondrial genome is not able to independently produce all of the proteins required for functionality; therefore, mitochondria rely on imported nuclear gene products;
  • the nuclear genome is made of 3.3 billion DNA base pairs, whereas the mitochondrial genome is built of 16,569 DNA base pairs;
  • the nuclear genome is linear, whereas the mitochondrial genome is circular.

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