Mitochondrial Genome: Evolution


Mitochondria, organelles that are responsible for producing energy for cell metabolism and also involved in cell death and ageing, contain their own genome. This genome has several unusual properties including a high copy number, a maternal and haploid mode of inheritance and a rapid rate of evolution. Recent advances in next‐generation sequencing methods have made it feasible to obtain complete mitochondrial deoxyribonucleic acid (mtDNA) genome sequences quickly and at low‐cost, providing new insights into human mtDNA variation and evolution. These methods also enable much more detailed studies of heteroplasmy across the entire mtDNA genome, which may be important in mtDNA‐associated diseases and cancer. It is also feasible to obtain complete mtDNA genome sequences from Neanderthals and other archaic humans, thereby providing further insights into human evolution.

Key Concepts:

  • Mitochondria have their own genome, which has a separate origin from the nuclear genome.

  • The mitochondrial genome has several unusual properties compared with the nuclear genome, including high copy number, maternal and haploid mode of inheritance and a rapid rate of evolution.

  • Next‐generation sequencing and other technical advances make it feasible to obtain complete mtDNA genome sequences rapidly and at low cost from large samples of individuals and are providing new insights into mtDNA variation and heteroplasmy.

  • MtDNA analyses support the hypothesis of a recent African origin of modern humans.

  • Archaic humans, such as Neandertals and Denisovans, did not contribute mtDNA to modern humans.

Keywords: mitochondrial DNA; evolution; human mtDNA variation; human origins; heteroplasmy; rate of mtDNA evolution; archaic humans; maternal inheritance

Figure 1.

The human mtDNA genome, with functional regions indicated as follows: two rRNA genes (12S and 16S); three genes for subunits of cytochrome oxidase (COI–COIII); seven genes for subunits of reduced form of nicotinamide adenine dinucleotide (NADH) dehydrogenase (N1–N6, N4L); two genes for subunits of F1 adenosine triphosphatase (ATPase) (6 and 8); the cytochrome b gene; 22 tRNA genes (designated by the standard single‐letter code); two origins of replication (OH and OL) and the control region (the major noncoding region).

Figure 2.

Schematic depiction of the phylogenetic relationships of mtDNA sequences from modern humans, Neanderthals and the Denisovan individual. Note that for modern humans, the phylogenetic tree divides into two primary branches, one consisting exclusively of African mtDNA types and the other consisting of some African mtDNA types and all non‐African mtDNA types. Numbers on branches indicate approximate divergence times (Ma, million years ago; Ka, thousand years ago).



Anderson S, Bankier AT, Barrell BG et al. (1981) Sequence and organization of the human mitochondrial genome. Nature 290: 457–465.

Awadalla P, Eyre‐Walker A and Smith JM (1999) Linkage disequilibrium and recombination in hominid mitochondrial DNA. Science 286: 2524–2525.

Barbieri C, Whitten M, Beyer K et al. (2012) Contrasting maternal and paternal histories in the linguistic context of Burkina Faso. Molecular Biology and Evolution 29: 1213–1223.

Barrell B, Bankier A and Drouin J (1979) A different genetic code in human mitochondria. Nature 282: 189–194.

Behar DM, Villems R, Soodyall H et al. (2008) The dawn of human matrilineal diversity. American Journal of Human Genetics 82: 1130–1140.

Briggs AW, Good JM, Green RE et al. (2009) Targeted retrieval and analysis of five Neandertal mtDNA genomes. Science 325: 318–321.

Brown W, George M and Wilson A (1979) Rapid evolution of animal mitochondrial DNA. Proceedings of the National Academy of Sciences of the USA 76: 1967–1971.

Cann RL, Stoneking M and Wilson AC (1987) Mitochondrial DNA and human evolution. Nature 325: 31–36.

Elson JL, Turnbull DM and Howell N (2004) Comparative genomics and the evolution of human mitochondrial DNA: assessing the effects of selection. American Journal of Human Genetics 74: 229–238.

Emerson BC (2007) Alarm bells for the molecular clock? No support for Ho et al's model of time‐dependent molecular rate estimates. Systematic Biology 56: 337–345.

Gray M, Burger G and Lang B (1999) Mitochondrial evolution. Science 283: 1476–1481.

Green RE, Krause J, Briggs AW et al. (2010) A draft sequence of the Neandertal genome. Science 328: 710–722.

Gunnarsdottir ED, Li M, Bauchet M, Finstermeier K and Stoneking M (2011) High‐throughput sequencing of complete human mtDNA genomes from the Philippines. Genome Research 21: 1–11.

Hasegawa M, Di Rienzo A, Kocher TD and Wilson AC (1993) Toward a more accurate time scale for the human mitochondrial DNA tree. Journal of Molecular Evolution 37: 347–354.

He Y, Wu J, Dressman DC et al. (2010) Heteroplasmic mitochondrial DNA mutations in normal and tumour cells. Nature 464: 610–614.

Ho SYW, Philipps MJ, Cooper A and Drummond AJ (2005) Time dependency of molecular rate estimates and systematic overestimation of recent divergence times. Molecular Biology and Evolution 22: 1561–1568.

Howell N, Smejkal CB, Mackey DA et al. (2003) The pedigree rate of sequence divergence in the human mitochondrial genome: there is a difference between phylogenetic and pedigree rates. American Journal of Human Genetics 72: 659–670.

Ingman M and Gyllensten U (2007) Rate variation between mitochondrial domains and adaptive evolution in humans. Human Molecular Genetics 16: 2281–2287.

Ingman M, Kaessmann H, Pääbo S and Gyllensten U (2000) Mitochondrial genome variation and the origin of modern humans. Nature 408: 708–713.

Jazin E, Soodyall H, Jalonen P et al. (1998) Mitochondrial mutation rate revisited: hot spots and polymorphism. Nature Genetics 18: 109–110.

Kaneda H, Hayashi J‐I, Takahama S et al. (1995) Elimination of paternal mitochondrial DNA in intraspecific crosses during early mouse embryogenesis. Proceedings of the National Academy of Sciences of the USA 92: 4542–4546.

Kivisild T, Shen P, Wall DP et al. (2006) The role of selection in the evolution of human mitochondrial genomes. Genetics 172: 373–387.

Krause J, Fu Q, Good JM et al. (2010) The complete mitochondrial DNA genome of an unknown hominin from southern Siberia. Nature 464: 894–897.

Kraytsberg Y, Schwartz M, Brown TA et al. (2004) Recombination of human mitochondrial DNA. Science 304: 981.

Krings M, Stone A, Schmitz RW et al. (1997) Neanderthal DNA sequences and the origin of modern humans. Cell 90: 19–30.

Kumar S, Hedrick PW, Dowling T and Stoneking M (2000) Questioning evidence for recombination in human mitochondrial DNA. Science 288: 1931a.

Leister D (2005) Origin, evolution and genetic effects of nuclear insertions of organelle DNA. Trends in Genetics 21: 655–663.

Li M, Schonberg A, Schaefer M et al. (2010) Detecting heteroplasmy from high‐throughput sequencing of complete human mitochondrial DNA genomes. American Journal of Human Genetics 87: 237–249.

Maricic T, Whitten M and Paabo S (2010) Multiplexed DNA sequence capture of mitochondrial genomes using PCR products. PLoS One 5: e14004.

Mishmar D, Ruiz‐Pesini E, Golik P et al. (2003) Natural selection shaped regional mtDNA variation in humans. Proceedings of the National Academy of Sciences of the USA 100: 171–176.

Nachman M and Crowell S (2000) Estimate of the mutation rate per nucleotide in humans. Genetics 156: 297–304.

Reich D, Green RE, Kircher M et al. (2010) Genetic history of an archaic hominin group from Denisova cave in Siberia. Nature 468: 1053–1060.

Schwartz M and Vissing J (2002) Paternal inheritance of mitochondrial DNA. New England Journal of Medicine 347: 576–580.

Stoneking M (1993) DNA and recent human evolution. Evolutionary Anthropology 2: 60–73.

Stoneking M and Krause J (2011) Learning about human population history from ancient and modern genomes. Nature Reviews Genetics 12: 603–614.

Sutovsky P, Moreno R, Ramalho‐Santos J et al. (2000) Ubiquitinated sperm mitochondria, selective proteolysis, and the regulation of mitochondrial inheritance in mammalian embryos. Biology of Reproduction 63: 582–590.

Tully LA, Parsons TJ, Steighner RJ et al. (2000) A sensitive denaturing gradient‐gel electrophoresis assay reveals a high frequency of heteroplasmy in hypervariable region 1 of the human mtDNA control region. American Journal of Human Genetics 67: 432–443.

Vigilant L, Stoneking M, Harpending H, Hawkes K and Wilson AC (1991) African populations and the evolution of human mitochondrial DNA. Science 253: 1503–1507.

Zischler H, Geisert H, von Haeseler A and Pääbo S (1995) A nuclear ‘fossil’ of the mitochondrial D‐loop and the origin of modern humans. Nature 378: 489–492.

Further Reading

Clayton D (2000) Vertebrate mitochondrial DNA – a circle of surprises. Experimental Cell Research 255: 4–9.

Falkenberg M, Larsson NG and Gustafsson CM (2007) DNA replication and transcription in mammalian mitochondria. Annual Review of Biochemistry 76: 679–699.

Garesse R and Vallejo C (2001) Animal mitochondrial biogenesis and function: a regulatory cross‐talk between two genomes. Gene 263: 1–16.

Ho SY and Gilbert MT (2010) Ancient mitogenomics. Mitochondrion 10: 1–11.

Lang B, Gray M and Burger G (1999) Mitochondrial genome evolution and the origin of eukaryotes. Annual Review of Genetics 33: 351–397.

Meikelejohn CD, Montooth KL and Rand DM (2007) Positive and negative selection on the mitochondrial genome. Trends in Genetics 23: 259–263.

Pakendorf B and Stoneking M (2005) Mitochondrial DNA and human evolution. Annual Review of Genomics and Human Genetics 6: 165–183.

Torroni A, Achilli A, Macaulay V, Richards M and Bandelt H‐J (2006) Harvesting the fruit of the human mtDNA tree. Trends in Genetics 22: 339–345.

Wallace DC (2007) Why do we still have a maternally inherited mitochondrial DNA? Insights from evolutionary medicine. Annual Review of Biochemistry 76: 781–821.

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How to Cite close
Stoneking, Mark(Apr 2013) Mitochondrial Genome: Evolution. In: eLS. John Wiley & Sons Ltd, Chichester. [doi: 10.1002/9780470015902.a0005074.pub3]