Table of Contents > Genomics > Mitochondrial genome Print

Mitochondrial genome


Related terms
Future research
Author information

Related Terms
  • Adenosine triphosphate, ATP, autoradiography, biogenesis, biomarker, deoxyribonucleic acid, DNA, electrophoresis, endosymbiotic theory, evolution, fluorescent imaging, forensic studies, maternal lineage test, migration patterns, mitochondria, mtDNA, mutation, oligonucleotide, organelle, oxidative phosphorylation, PCR, phylogenetic tool, polymerase chain reaction, polymorphism, primer, restriction fragment length polymorphism, RFLP, sequencing, single nucleotide polymorphism, somatic mutation, SNP.

  • Genes, or segments of deoxyribonucleic acid/DNA, are considered the building blocks of life because they provide instructions for all of the cells in the body. They are located inside cells, and they control an organism's development and functions by instructing cells to make new molecules, usually proteins. Proteins are organic compounds composed of amino acids, and the sequence of the amino acids in a protein is defined by a gene. Genes are passed down from parents to their children. A genome is the sum total of the genetic information in an organism.
  • DNA is a long, thread-like molecule made up of many nucleotides. The sequence of bases in DNA serves as the carrier of genetic (hereditary) information. Nucleotides are molecules composed of a nitrogen-containing base, a 5-carbon sugar, and one or more phosphate groups. Long strands of nucleotides form nucleic acids. A chromosome is a long DNA molecule that carries the hereditary information of an organism. Ribonucleic acid, or RNA, is a nucleic acid that helps in protein synthesis, which is important for the growth and maintenance of the body. RNA is formed under the direction of DNA, and both help to form amino acids, which are the building blocks of protein.
  • Mitochondria are rod-shaped organelles (subunits of cells) that are often called the powerhouse of the cell. Mitochondria convert nutrients into energy for the cell through a process called oxidative phosphorylation. They are the energy-producing structures of the cell. Oxidative phosphorylation uses oxygen, enzymes, and simple sugars to form adenosine triphosphate (ATP), the main energy source of the cell. Most organisms, except bacteria and blue-green algae, have mitochondria inside their cells. Every cell contains hundreds to thousands of mitochondria, which are located in the fluid that surrounds the nucleus, called the cytoplasm. Mitochondria possess two sets of membranes: a smooth continuous outer membrane and an inner membrane arranged in folds.
  • Apart from energy production, mitochondria also play a part in several cellular activities, such as the regulation of the self-destruction of cells, known as apoptosis (a normal process), and they also help produce of substances like cholesterol and heme (a component of hemoglobin, the molecule that carries oxygen in the blood).
  • Structure: A mitochondrial genome is the genetic material of the mitochondria. Although most of the DNA is contained in the chromosomes within the nucleus, mitochondria also have a small amount of their own DNA; the DNA present in mitochondria is known as mitochondrial DNA or mtDNA.
  • The human mitochondrial genome is a circular DNA that contains 37 genes and is 16,569 base pairs (bp) in length, which is less than the DNA present in the nucleus (33,400,000 bp). Thirteen of the 37 genes provide instructions for making enzymes involved in energy production, and the remaining genes provide instructions for making molecules known as transfer RNA (tRNA) and ribosomal RNA (rRNA). These types of RNA help assemble amino acids into functioning proteins and thus help in protein synthesis.
  • Evolution: Evolution is the process of change in the inherited traits of an organism from one generation to another. Some researchers have suggested endosymbiotic theory as the reason for the mitochondria having their own genome. According to this theory, mitochondria originated or developed from bacteria. The theory suggests that mitochondria were independent living cells similar to bacteria millions of years ago. The bacteria invaded primitive amoeboid cells and established a mutually beneficial relationship known as symbiosis. The primitive amoeboid cells are the ancestors of today's eukaryotic cells, which are cells organized into complex structures contained within a membrane. Millions of years later, some of the redundant genes were no longer present in the bacteria. As a result, they became dependent on their hosts. A host is an animal or plant on which or in which another organism lives. Thus, the mitochondria containing few genes ceased to exist as independent life forms.
  • Uses: The high concentration of mtDNA in cells makes it useful for analyzing samples that have low nuclear DNA concentrations (when only small sample is available) or are old and degraded, such as those that have lost most of the nuclear DNA. Hence, mtDNA is used in forensic studies, which involve the relation and application of medical facts to legal matters.
  • Studying the mitochondrial genome is important because a number of rare diseases are caused by mutations, or abnormalities, in mtDNA. The tissues most commonly affected are the brain and nervous system, muscles, kidneys, and liver. The clinical manifestations of the diseases may vary depending on the proportion of abnormal mtDNA present.
  • Mitochondrial diseases are passed from the mother to the child, or maternally inherited, because all of the mitochondria in the developing human embryo come from the egg. Although the sperm contains mitochondria in its tail, the tail falls off when the sperm attaches to the egg during fertilization. Hence, the embryo does not contain the mitochondria from sperm and mitochondrial diseases are maternally inherited.
  • Although a mother with an mtDNA mutation passes that mutation to all her children, not all of them may necessarily become symptomatic (exhibit symptoms of the mutation/disease). Also, depending on the percentage of mutant mtDNA acquired by each child, the disease can manifest itself in different forms.
  • Analyzing the maternal genome helps in the early identification of mitochondrial diseases in high-risk individuals. This type of research also aids in the development of new therapies for mitochondrial diseases.
  • Mitochondrial DNA sequencing provides researchers with a useful tool for studying human migration patterns (geographic locations), human diseases, evolution, maternally-linked relationships, and human identification in criminal cases and the identification of remains of victims of mass disaster (forensic testing).

  • General: Mitochondrial genome analysis requires a patient's DNA sample, which is obtained from blood or tissues such as hair, bone, teeth, etc. Studying the mitochondrial genome helps in the early detection and monitoring of disease progression because a number of rare diseases are caused by mutations in mitochondrial DNA (mtDNA).
  • Mutations or polymorphisms of the mtDNA increase the risk of developing several diseases. A permanent variation in a DNA sequence of a gene is called as mutation. Genetic changes or mutations that occur in more than 1% of the general population are called polymorphisms. Gene mutations may occur in two ways: mutations that are passed on from parents to children are called hereditary mutations, and mutations occurring in the DNA of individual cells at some time during a person's life are called acquired or somatic mutations. A somatic mutation may occur in the general body cells as opposed to the germ cells (also called sex cells). Therefore, somatic mutations are not transmitted to offspring.
  • Sample preparation and mtDNA extraction: The patient's DNA sample is placed in a solution containing some chemicals, such as sucrose, hydrochloric acid, ethylene glycol, and tetraacetic acid, which break down the mitochondria, leading to the release of mtDNA. A sample preparation is done to isolate the mtDNA by removing the potential contaminants in the sample. The solution is separated using certain chemicals and then filtered, leaving the mtDNA completely free of the mitochondria and other biological molecules such as proteins. Then, several copies of the extracted mtDNA are produced (amplification) using polymerase chain reaction (PCR) to help detect any mutation(s) in the mtDNA.
  • Polymerase chain reaction (PCR): PCR is an efficient and sensitive enzymatic laboratory technique used to amplify a specific sequence of DNA into billions of its copies in the presence of sequence-specific oligonucleotide primers and Taq DNA polymerase (enzyme). Oligonucleotide primer is a sequence of nucleotides, usually of 20-50 bases, which is complementary to a specific DNA sequence and serves as a starting point for DNA replication. Taq DNA polymerase is an enzyme that synthesizes new DNA strands using preexisting DNA strands as a template, thereby replicating the DNA.
  • Taq DNA polymerase, a type of DNA polymerase, is named after the bacterium, Thermus aquaticus. It can withstand the high temperature used in PCR and is thus the enzyme usually used in PCR. A DNA-binding dye (e.g., SYBR Green) that binds to mtDNA is also added, causing fluorescence (illumination) of the dye, thereby facilitating easier detection. Fluorescent dye is a substance that selectively combines with certain components and then illuminates upon irradiation with ultraviolet or violet-blue light.
  • DNA sequencing: Some of the polymorphisms associated with mtDNA are as a result of single nucleotide polymorphisms (SNPs), which are DNA sequence variations that occur when a single nucleotide in the genome sequence is altered. DNA sequencing is a process in which the precise sequence of nucleotides in a sample of DNA is determined. Nucleotides are the building blocks of DNA in a sequence, and they are made of nitrogenous bases, sugars, and phosphates. DNA sequencing as a scanning method for SNPs has become popular with the development of automated DNA sequencers and newer detection methods. Usually, Sanger's (dideoxy or chain termination method) automated method is used to analyze the DNA sequences. The steps involved in the process are described below.
  • The initial step involves the extraction of high-quality DNA from the sample of interest, followed by polymerase chain reaction (PCR) in the presence of fluorescent labeled (attached) dideoxynucleotide triphosphate (ddNTP). DNA purification is the process of rendering the DNA pure (i.e. clean of foreign elements). A high-quality DNA is one in which all the contaminants, such as other proteins, are removed from the sample, thereby ensuring the production of accurate results. ddNTPs are synthetic nucleotides that are structurally somewhat different from the regular nucleotides and function as DNA chain terminators during the synthesis of a DNA sequence. The end reaction product is a set of DNA sequences differing in length by one nucleotide, and the last nucleotide base in each sequence is the unique fluorescent labeled ddNTP.
  • The reaction products are run on the electrophoresis, which separates the DNA fragments based on their size. During this process, the fluorescent signals produced by the labeled nucleotides are detected by the fluorescent detection systems, thereby identifying the nucleotide base. These fluorescent signals are fed and analyzed by a computer, giving out the exact sequence of DNA. The whole process is automated and the resultant DNA sequence is compared with other sequences by various computer programs, thereby spotting the mutations in the sample DNA sequence.
  • The automated DNA sequencers are efficient in detecting gene mutations. The advantage of direct DNA sequencing is that it provides the complete information about the DNA sequence in a single experiment such as the type of the mutation and the exact location of the mutation on the DNA sequence.
  • Restriction fragment length polymorphism (RFLP): RFLP may be used in combination with PCR or directly on the purified DNA for analyzing the DNA sequence. RFLP is a molecular laboratory technique in which the mitochondrial DNA from a sample is cut (cleaved) into fragments of DNA sequence by enzymes called restriction endonucleases. These enzymes cleave the DNA sequences at specific sites (recognition restriction sites), resulting in characteristic fragments of DNA of different length and strand orientation.
  • The fragmented DNA are put on gel electrophoresis and separated based on their size and electric charges as they migrate through the gel to form distinct bands. The separated DNA fragments are then paired with (hybridized) complementary sequence of DNA called probes. The probes have specific sequences of nucleotides, which are complementary to specific DNA fragments (target sequences) to which they get hybridized. A complementary strand is a nucleic acid sequence that can form a double-stranded structure by matching base pairs (adenine (A) with guanine (G); cytosine (C) with thymine (T)); for example, the complementary strand for G-T-A-C is C-A-T-G. These special probes are tagged with a radioactive dye, facilitating their detection by autoradiography. Autoradiography is a technique where the PCR products are labeled with radioactive molecules that can be visualized upon exposure to X-rays.
  • The RFLP analysis technique is a slow and cumbersome method requiring a large sample DNA. However, with the development of PCR and its automation, certain limitations of RFLP have been overcome, as PCR can amplify minute quantities of biologic material to provide adequate specimens (PCR products) for further analysis. Also, the advancement in detection techniques such as fluorescent imaging has made RFLP more efficient in the detection of mitochondrial DNA mutations.

  • General: A broad spectrum of disease manifestations have been associated with systemic mitochondrial DNA (mtDNA) mutations. A permanent variation in a DNA sequence of a gene is called as mutation. These mutations can be either single-point mutations or large rearrangements (deletions and/or duplications), both of which may lead to the development of diseases. A single-point mutation involves changes in a single nucleotide and may consist of the loss of a nucleotide, substitution of one nucleotide for another, or the insertion of an additional nucleotide. Nucleotides, the building blocks of DNA, are made of nitrogenous bases, sugars, and phosphate. Nitrogenous bases are of two types: purines, such as adenine (A) and guanine (G), and pyrimidines, such as cytosine (C) and thymine (T). Mitochondrial DNA mutations may occur if the mitochondrial DNA polymerase makes errors during DNA replication. Because genes outside of the mitochondria (in the nuclear chromosomes) control mitochondrial growth and division, nuclear DNA mutations may also cause mutations in mitochondrial DNA. Large rearrangements are also possible through DNA recombination events, though mitochondrial DNA typically only recombines with other mitochondrial DNA (and not with chromosomal DNA). Regardless of how they occur, mutations in mitochondrial DNA are usually maternally inherited.
  • Currently, research is being carried out to examine the role of mtDNA in the development of several diseases.
  • Multiple sclerosis: Multiple sclerosis (MS) is a chronic (long-term), progressive, degenerative disorder that affects nerve fibers in the brain and spinal cord. Multiple sclerosis is widely believed to be an autoimmune disease, a condition in which the immune system attacks components of the body as if they are foreign. Scientists have conducted studies to investigate if the mitochondrial genetic factors influence the susceptibility to MS. They have found evidence that variation in mtDNA may act as a risk factor for the future development of MS.
  • Depression: Previous studies have indicated that adults, who have mitochondrial disorders, have a high risk of developing depression later in their life. More recently, researchers have found that individuals between 10 and 20 years of age with major depression have been later identified to have a mitochondrial disorder. Further research is required to examine the association between depression and mitochondrial disorder.

  • General: Studying the mitochondrial genome is important because a number of rare diseases are caused by mutations in mitochondrial DNA (mtDNA). A mutation is a change in the sequence of base pairs in the DNA that makes up a gene.
  • A broad spectrum of disease manifestations has been associated with mitochondrial DNA (mtDNA) mutations. Mitochondrial disorders are most commonly manifested as neuromuscular disorders, including developmental delay, seizure disorders, skeletal muscle weakness, and cardiomyopathy (a disease of the heart muscle). Some of the mitochondrial disorders are inherited, but most are not because few mitochondrial mutations occur when the embryo is developing in the womb. Examples of inherited mitochondrial diseases include Leber's hereditary optic neuropathy (LHON) and Kearns-Sayre syndrome. LHON causes progressive vision loss and is often combined with heart problems. Kearns-Sayre syndrome involves paralysis of the eye muscles, dementia, and seizures. Mutations in mtDNA may also lead to diseases/disorders such as deafness, sudden-onset (acute) liver failure, diabetes mellitus, and hormonal deficiencies.
  • Age-related mtDNA somatic mutations: A somatic mutation is a mutation occurring in the general body cells as opposed to the germ cells (sex cells). Therefore, these mutations are not transmitted to progeny/offspring. These mutations in mtDNA may enhance the production of potentially harmful molecules called reactive oxygen free radicals. Free radicals are formed when oxygen reacts with certain molecules in the body. Previous studies have suggested that 2-15% of the total oxygen intake during rest and exercise may convert into free radicals. They may be formed as a byproduct of normal oxygen metabolism. The presence of the radicals increases during times of environmental stress such as during heat exposure.
  • Metabolism is the sum of anabolism, the process by which energy is produced and maintained, and catabolism, the process by which energy is made available to an organism. Oxygen free radicals damage mtDNA, causing modifications of DNA bases and rearrangements. A free radical is a very reactive atom or molecule typically possessing a single unpaired electron. Free oxygen radicals are reactive due to the unpaired electron and may cause damage to proteins, fats, and DNA. The accumulation of these somatic mutations during life may cause certain changes leading to cell death, or apoptosis, and normal aging. Deletions and mutations due to free radicals have been associated with the aging process involved in oxygen-dependent tissues such as the brain, heart, muscles, and kidneys. Also, oxidative stress has been implicated in degenerative nervous system diseases such as Alzheimer's (a type of dementia) and Parkinson's disease (a progressive nervous system disease). Oxidative stress is a physiological stress on the body that is caused by the cumulative damage done by free radicals. Thus, the identification of mitochondrial mutations may help in the early diagnosis of these diseases; consequently, treatment could be started at an early stage, providing better outcomes.
  • Biomarkers: Genetic biomarkers provide estimates of how genetic variations, also called mutations or polymorphisms, make individuals susceptible to environmental agents. They can help predict disease susceptibility, prognosis, and treatment response and toxicity. There are several biological characteristics of the mitochondrial genome (mtgenome) that make it suitable for early detection and monitoring of cancer. A genome is the sum total of the genetic information in an organism.
  • The mtgenome has an accelerated mutation rate in comparison to the nuclear genome. The mitochondrial genome has a high copy number; there are potentially thousands of mtgenomes per cell that assist in the easy identification of important biomarkers, even when only low amounts of samples are available. In the absence of mutations, all the mtgenomes are identical.
  • Identification of the single nucleotide polymorphisms (SNP), which are DNA sequence variations that occur when a single nucleotide in the genome sequence is altered, is important. Nucleotides are building blocks of DNA. SNPs may act as biological markers. In this way, they help locate genes that are associated with disease. SNPs may also be used to track the inheritance of disease genes within families, thereby assisting in the evaluation of an individual's risk of developing a disease.
  • Phylogenetic tool: The mtDNA sequence variation may be used to construct a phylogenetic or evolutionary tree (a diagram/tree showing the evolutionary relationship between individual sequences). It serves as a phylogenetic tool to analyze the events in human prehistory. The theory of evolution is the process of change in the inherited traits of an organism from one generation to another. Moreover, the geographical distribution of the lineages on a tree may be used to detect prehistoric movements from one region to another facilitating the study of the migration of humans over time.
  • Maternal lineage test: Maternal lineage is a test done to examine the relationship of an individual to relatives or ancestors. It may also be used to determine the biological mother if there is a question of maternity. It is commonly used as a maternal lineage test for legal purposes.
  • Forensic marker: The analysis of mtDNA, like the DNA present in the nucleus, helps confirm the identification of human remains. It may assist in criminal cases because it may also be used to provide evidence about the identity of the crime victims and the perpetrators of crime who leave any biological material, such as hair shafts, at crime scenes.
  • Additionally, mtgenome analysis may aid in the identification of the remains of victims of mass disaster. For example, the Armed Forces DNA Identification Laboratory (AFDIL) has used it to help identify the remains of soldiers from the Vietnam War, as well as victims of plane crashes and other disasters.

  • One major limitation of mitochondrial genome sequencing to determine maternal lineage (blood-related members of the family) is that maternal relatives will not always show identical mtDNA sequences. Also, different tissues from a single individual (e.g., hair versus blood) may have different mtDNA sequences. Hence, the test results may not always be accurate. Because of this, the mtDNA analysis is done mainly for investigation and exclusion purposes and is later confirmed with other forensic analysis tests. Forensic study involves the relation and application of medical facts to legal matters.
  • In forensic studies, contamination is a crucial issue for mtDNA analysis because there are no standardizations regarding the frequency and level of contamination necessary to invalidate sequence comparisons. Hence, researchers are not sure as to how often they might expect errors in mtDNA comparisons. This is a common problem and generally difficult to avoid, even if the samples are from the same tissue type since there may be external causes of DNA contamination (due to chemicals).
  • The disadvantage of using DNA sequencing to detect single nucleotide polymorphisms (SNP), which are DNA sequence variations that occur when a single nucleotide in the genome sequence is altered, is that it requires very high-quality DNA and is expensive. This has been overcome by automation.
  • Another major drawback with this method is that only about 400 base pairs (bp) of sequencing data can be generated by DNA sequencing in a series of experiments, restricting it to smaller fragments sizes, thereby increasing the cost and time.


Future research
  • Evolution: The mitochondrial genome sequences from extinct Neanderthal specimens are being studied to learn about the possible evolution of modern-day humans. Neanderthals are specimens of the Homo genus, the same as humans, which inhabited Europe and Central Asia as early as 350,000-500,000 years ago. According to the theory of evolution, the genetic makeup of a population changes during successive generations as a result of natural selection.
  • A complete mitochondrial (mt) genome sequence was reconstructed from a 38,000-year-old Neanderthal individual. Since the scientists found evidence that Neanderthal mtDNA was decreased in comparison with other primate lineages, it was speculated that the effective population size of Neandertals was small.
  • Mitochondrial biogenesis: Biogenesis means that a living organism can only originate from a living organism similar to itself. Mitochondrial biogenesis is the process by which mitochondria increase their ability to make adenosine triphosphate (ATP), the main energy source of the cell, by synthesizing additional respiratory enzyme complexes anywhere in the body. Although several studies have been conducted, the sites of mitochondria biogenesis remain uncertain. Some studies have suggested that mitochondrial DNA (mtDNA) replication/multiplication occurs mainly in the cell body, while certain recent studies have indicated that biogenesis of mitochondria is not limited to the cell body and can take place in axons (parts of nerve cell). Further research is required to examine the findings.

Author information
  • This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (

  1. Amiri M, Hollenbeck PJ. Mitochondrial biogenesis in the axons of vertebrate peripheral neurons. Dev Neurobiol. 2008 Jul 29;doi 10.1002/dneu.20668.
  2. Ban M, Elson J, Walton A, et al. Investigation of the role of mitochondrial DNA in multiple sclerosis susceptibility. PLoS ONE. 2008 Aug 6;3(8):e2891.
  3. Clark AG. Genome sequences from extinct relatives. Cell. 2008 Aug 8;134(3):388-9.
  4. DNA Bioscience.
  5. Genetics Home Reference.
  6. Green RE, Malaspinas AS, Krause J, et al. A complete neandertal mitochondrial genome sequence determined by high-throughput sequencing. Cell. 2008 Aug 8;134(3):416-26.
  7. Jakupciak JP, Maggrah A, Maragh S, et al. Facile whole mitochondrial genome resequencing from nipple aspirate fluid using MitoChip v2.0. BMC Cancer. 2008 Apr 10;8:95.
  8. Koene S, Kozicz TL, Rodenburg RJ, et al. Major depression in adolescent children consecutively diagnosed with mitochondrial disorder. J Affect Disord. 2008 Aug 8;doi 10.1016/j.jad.2008.06.023.
  9. Natural Standard: The Authority on Integrative Medicine. .
  10. The Human Genome.

Copyright © 2011 Natural Standard (

The information in this monograph is intended for informational purposes only, and is meant to help users better understand health concerns. Information is based on review of scientific research data, historical practice patterns, and clinical experience. This information should not be interpreted as specific medical advice. Users should consult with a qualified healthcare provider for specific questions regarding therapies, diagnosis and/or health conditions, prior to making therapeutic decisions.

Search Site