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Difference between Mitochondrial DNA and Nuclear DNA

Difference between Mitochondrial DNA and Nuclear DNA

What is DNA?

Deoxyribonucleic acid (DNA) carries genetic information that is used as a set of instructions for growth and development, as well as the ultimate functioning and reproduction of living organisms. It is a nucleic acid and is one of the four major types of macromolecules that are known to be essential for all forms of life1.

Each DNA molecule is comprised of two biopolymer strands coiling around each other to form a double helix. These two DNA strands are called polynucleotides, as they are made of simpler monomer units called nucleotides2.

Each individual nucleotide is composed of one of four nitrogen-containing nucleobases – Cytosine (C), Guanine (G), Adenine (A) or Thymine (T) – along with a sugar called deoxyribose and a phosphate group.

Nucleotides are joined to one another by covalent bonds, between the phosphate of one nucleotide and the sugar of the next. This creates a chain, resulting in an alternating sugar-phosphate backbone. Nitrogenous bases of the two polynucleotide strands are bound together by hydrogen bonds, to make double stranded DNA according to strict base pairings (A to T and C to G)3.

Within eukaryotic cells, DNA is organised into structures called chromosomes, with each cell having 23 pairs of chromosomes. During cell division, chromosomes are duplicated through the process of DNA replication, as long as each cell has its own complete set of chromosomes. Eukaryotic organisms such as animals, plants and fungi, store the majority of their DNA inside the cell nucleus and some of their DNA in organelles such as mitochondria4.

Being located in different regions of the eukaryotic cell, there are a number of fundamental differences between mitochondrial DNA (mtDNA) and nuclear DNA (nDNA). Based on key structural and functional properties, these differences affect how they operate within eukaryotic organisms.

Organization and structural differences of  Mitochondrial DNA and Nuclear DNA

  • Location → Located exclusively in the mitochondria, mtDNA contains 100-1,000 copies per somatic cell. Nuclear DNA is located within the nucleus of every eukaryotic cell (with some exceptions such as nerve and red blood cells) and usually only has two copies per somatic cell5.
  • Structure Both types of DNA are double stranded. However, nDNA has a linear, open ended structure that is enclosed by a nuclear membrane. This differs from mtDNA, which usually has a closed, circular structure and is not enveloped by any membrane6
  • Genome sizes → Both mtDNA and nDNA have their own genomes but are very different sizes. In humans, the size of the mitochondrial genome consists of only 1 chromosome that contains 16,569 DNA base pairs7. The nuclear genome is significantly larger than the mitochondrial, consisting of 46 chromosomes that contain 3.3 billion nucleotides.
  • Gene encoding The singular mtDNA chromosome is much shorter than the nuclear chromosomes. It contains 36 genes that encode for 37 proteins, all of which are specific proteins used in the metabolic processes mitochondria undertake (such as citrate acid cycle, ATP synthesis and fatty acid metabolism). The nuclear genome is much larger, with 20,000-25,000 genes coding for all the proteins required for its function, which also includes mitochondrial genes. Being semi-autonomous organelles, mitochondrion cannot code for all of its own proteins. However, they can encode for 22 tRNAs and 2 rRNAs, which nDNA lacks the capability to do6.

Functional differences

  • Translation process The translation process between nDNA and mtDNA can vary. nDNA follows the universal codon pattern, however this is not always the case for mtDNA. Some mitochondrial coding sequences (triplet codons) do not follow the universal codon pattern when they are translated into proteins. For example, AUA codes for methionine in mitochondrion (not Isoleucine). UGA also codes for tryptophan (not a stop codon as in mammalian genome)6.
  • Transcription process → Gene transcription within mtDNA is polycistronic, meaning an mRNA is formed with sequences that code for many proteins. For nuclear gene transcription the process is monocistronic, where the mRNA formed has sequences coding for only a single protein8.
  • Genome inheritance → Nuclear DNA is diploid, meaning it inherits DNA both maternally and paternally (23 chromosomes from each of the mother and father). However, mitochondrial DNA is haploid, with the single chromosome being inherited down the maternal side and does not undergo genetic recombination9.
  • Mutation rate As nDNA undergoes genetic recombination, it is a shuffle of the parent’s DNA and is therefore altered during inheritance from the parents to their offspring. However, as mtDNA is only inherited from the mother, there is no alteration during transmission, meaning any DNA changes come from mutations. The mutation rate in mtDNA is much higher than in nDNA, which is normally less than 0.3%10.

Differences in the application of mtDNA and nDNA within science

The different structural and functional properties of mtDNA and nDNA, have led to differences in their applications within science. With its significantly greater mutation rate, mtDNA has been utilized as a powerful tool for tracking ancestry and lineage through females (matrilineage). Methods have been developed that are used to track the ancestry of many species back through hundreds of generations and has become the mainstay of phylogenetics and evolutionary biology.

Difference between Mitochondrial DNA and Nuclear DNA-1

Due to the higher mutation rate, mtDNA evolves much faster than nuclear genetic markers11. There are many variations among the codes used by mtDNA that arise from mutations, many of which are not harmful to their organisms. Utilizing this greater mutation rate and these non-harmful mutations, scientists determine mtDNA sequences and compare them from different individuals or species.

A network of relationships among these sequences is then constructed which provides an estimate of the relationships among either the individuals or species from which the mtDNA was taken. This gives an idea of how closely and distantly related each is – the more mtDNA mutations that are the same in each of their mitochondrial genomes, the more related they are.

Due to the lower mutation rate of nDNA, it has a more restricted application in the field of phylogenetics. However, given the genetic instructions it holds for the development of all living organisms, scientists have recognised its use in forensics.

Every single person has a unique genetic blueprint, even identical twins12. Forensic departments are able to use polymerase chain reaction (PCR) techniques, using nDNA, to compare samples in a case. This involves using small amounts of nDNA to make copies of targeted regions called short tandem repeats (STRs) on the molecule13. From these STRs, a ‘profile’ is obtained from items of evidence, which can then be compared to known samples taken from the individuals involved in the case.

Human mtDNA can also be used to help identify individuals using forensics, however unlike nDNA, it is not specific to one individual but can be used in combination with other evidence (such as anthropological and circumstantial evidence) to establish identification. Because mtDNA has a greater number of copies per cell than nDNA, it has the ability to identify much smaller, damaged or degraded biological samples14. The greater number of mtDNA copies per cell than nDNA, also makes it is possible to obtain a DNA match with a living relative, even if numerous maternal generations separate them from the skeletal remains of a relative15.

Tabular comparison of key differences between Mitochondrial and Nuclear DNA

Mitochondrial DNA Nuclear DNA
Location Mitochondria Cell Nucleus
Copies per somatic cell 100-1,000 2
Structure Circular and closed Linear and open ended
Membrane enclosure Not enveloped by a membrane Enclosed by a nuclear membrane
Genome size 1 chromosome with 16,569 base pairs 46 chromosomes with 3.3 billion base pairs
Number of genes 37 genes 20,000-25,000 genes
Method of inheritance Maternal Maternal and Paternal
Method of translation Some codons do not follow universal codon pattern Follows universal codon pattern
Method of transcription Polycistronic Monocistronic

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References :

[0]University, M. S. (2017). Nucleic Acids. Available at: http://www2.chemistry.msu.edu/faculty/reusch/VirtTxtJml/nucacids.htm. (Accessed: 3rd August 2017)

[1]Alberts, B. et al. (2014). Molecular Biology of the Cell.

[2]Yakovchuk, P., Protozanova, E. & Frank-Kamenetskii, M. D. (2006). Base-stacking and base-pairing contributions into thermal stability of the DNA double helix. Nucleic Acids Res. 34(2), 564–574

[3]Russell, P. (Benjamin Cummings, 2001). iGenetics.

[4]Miller, F. J., Rosenfeldt, F. L., Zhang, C., Linnane, A. W. & Nagley, P. (2003). Precise determination of mitochondrial DNA copy number in human skeletal and cardiac muscle by a PCR-based assay: lack of change of copy number with age. Nucleic Acids Res. 31(11), e61

[5]Taanman, J.-W. (1999). The mitochondrial genome: structure, transcription, translation and replication. Biochim. Biophys. Acta - Bioenerg. 1410(2), 103–123

[6]Anderson, S. et al. (1981). Sequence and organization of the human mitochondrial genome. Nature 290(5806), 457–65

[7]Clayton, D. A. (2000). Transcription and replication of mitochondrial DNA. Hum. Reprod. 15(Suppl 2), 11–17

[8]Sato, M. & Sato, K. (2013). Maternal inheritance of mitochondrial DNA by diverse mechanisms to eliminate paternal mitochondrial DNA. Biochim. Biophys. Acta - Mol. Cell Res. 1833(8), 1979–1984

[9]Brown, W. M., George, M. & Wilson, A. C. (1979). Rapid evolution of animal mitochondrial DNA. Proc. Natl. Acad. Sci. U. S. A. 76(4), 1967–71

[10]Orlando, F. (Academic Press, 1993). Molecular phylogenetics and evolution. Molecular phylogenetics and evolution

[11]Casselman, A. Identical Twins’ Genes Are Not Identical. Scientific American Available at: https://www.scientificamerican.com/article/identical-twins-genes-are-not-identical/. (Accessed: 3rd August 2017)

[12]Apprehension, B. of C. (2017). Forensic Science - Nuclear DNA. Available at: https://dps.mn.gov/divisions/bca/bca-divisions/forensic-science/Pages/dna-nuclear.aspx. (Accessed: 3rd August 2017)

[13]Budowle, B., Allard, M. W., Wilson, M. R. & Chakraborty, R. (2003). FORENSICS AND MITOCHONDRIAL DNA: Applications, Debates, and Foundations. Annu. Rev. Genomics Hum. Genet. 4(1), 119–141

[14]National Institute of Justice. (2017). Forensic DNA: Mitochondrial DNA. Available at: https://www.nij.gov/topics/forensics/evidence/dna/research/pages/mitochondrial.aspx. (Accessed: 3rd August 2017)



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