Evolutionary Biology and Mitochondrial Genomics: 50 000 Mitochondrial DNA Genomes and Counting


Mitochondrial deoxyribonucleic acid (mtDNA) is a small circular piece of deoxyribonucleic acid (DNA) that resides inside of mitochondria in the cytoplasm of most eukaryotic cells. It has been used by evolutionary biologists for nearly four decades as an analytical tool for everything from tracing human lineages and how people moved across the planet to studies about natural selection. More recently, mtDNA has become even more useful in evolutionary biology as a result of the ease with which the entire molecule can be sequenced. Large numbers of fully sequenced mitochondrial genomes have been generated as a result of next‐generation sequencing (NGS) and powerful bioinformatic approaches.

Key Concepts

  • Mitochondrial DNA has been used to study evolutionary biology for nearly four decades.
  • The capacity to sequence whole mitochondrial genomes has become an important part of the expansion of the role of this molecule in evolutionary biology.
  • MtDNA genome information has contributed to the study of human mtDNA haplogroup studies, animal phylogeography and phylogenetic studies, ancient DNA studies, studies of natural selection and studies of nuclear mitochondrial interactions.
  • As of 2017, over 500 ancient human mtDNA genomes have been sequenced.
  • As of 2017, over 100 ancient animal mtDNA genomes have been sequenced.
  • An important new area where mtDNA genomics will contribute in the future is in using DNA sequence analysis of natural history collection specimens.

Keywords: mitochondrial DNA; genomics; natural selection; ancient DNA; evolution; mitonuclear interactions

Figure 1. Global distribution of human paleo mtDNA (mitochondrial deoxyribonucleic acid) genomes. The age of the specimen from which the mtDNA genome was sequences is given in the legend with colours. Each circle represents a single genome from Homo sapiens. Diamonds and squares represent Neanderthal and Denisova, respectively.
Figure 2. Plot of the number of mtDNA genomes in the database for six major groups of animals (orange line). The blue line represents the total number of named described species for the group.
Figure 3. Phylogenetic tree showing the geographic distribution of paleo specimens where mtDNA genomes have been generated. The geographic location is given by the colour of the open circles. The age of the paleo specimen is given by its position in the grid to the right of the tree.
Figure 4. Plots of percentage of sites under selection in 12 protein‐coding genes (listed on the X‐axis) in the mtDNA genome. The percentage of sites under selection were plotted in two ways. The first approach (blue bars) uses the raw number of positions in each gene divided by the number of bases in each gene summed over the 36 animal groups included in the survey. The second approach (orange bars) simply counts the number of animal groups per gene with positively selected sites divided by the number of bases in each gene summed over the 36 animal groups in the survey. The blue dotted box shows the Complex V genes (Atp6 and Atp8) and the red box shows the three Complex I genes (ND2, ND4 and ND5) that are show high levels of positive selection. The green box shows the low‐level positively selected Complex IV genes.
Figure 5. Structure of animal mtDNA genomes. The largest animal mtDNA genomes are circular and more than 40 kb in size, while the smallest are less than 10 kb in size. mtDNA genome linearisation and fragmentations have occurred as a synapomorphy in the Medusozoa but are also found as an exception in some Porifera. With respect to the gene inventory, the most complete mtDNA genomes are found in placozoans, while the derived Ctenophora show the most incomplete genomes. Within the Bilateria, similar secondary fragmentations of the mtDNA genome are observed in some arthropods but with the structure remains circular. Substantial secondary expansions due to duplication events of whole mtDNA genome regions are found in some molluscs. tRNA abbreviations CS (complete set of tRNAs), GCS (generally complete set of tRNAs), IS (incomplete set of tRNAs).


Avise JC, Arnold J, Martin Ball R, et al. (1987) Intraspecific phylogeography: the mitochondrial DNA bridge between population genetics and systematics. Annual Review of Ecology and Systematics 18 (1): 489–522.

Bar‐Yaacov D, Blumberg A and Mishmar D (2012) Mitochondrial‐nuclear co‐evolution and its effects on OXPHOS activity and regulation. Biochimica et Biophysica Acta 1819 (9): 1107–1111.

Baris TZ, Wagner DN, Dayan DI, et al. (2017) Evolved genetic and phenotypic differences due to mitochondrial‐nuclear interactions. PLoS Genetics 13 (3): e1006517.

Bernt M, Braband A, Schierwater B and Stadler PF (2013a) Genetic aspects of mitochondrial genome evolution. Molecular Phylogenetics and Evolution 69: 328–338.

Bernt M, Donath A, Jühling F, et al. (2013b) MITOS: improved de novo metazoan mitochondrial genome annotation. Molecular Phylogenetics and Evolution 69 (2): 313–319.

Boyer F, Mercier C, Bonin A, et al. (2016) Obitools: a unix‐inspired software package for DNA metabarcoding. Molecular Ecology Resources 16 (1): 176–182.

Bridge D, Cunningham CW, Schierwater B, DeSalle R and Buss LW (1992) Class‐level relationships in the phylum Cnidaria: evidence from mitochondrial genome structure. Proceedings of the National Academy of Sciences 89 (18): 8750–8753.

Buerki S and Baker WJ (2016) Collections‐based research in the genomic era. Biological Journal of the Linnean Society 117: 5–10.

Cameron SL (2014) Insect mitochondrial genomics: implications for evolution and phylogeny. Annual Review of Entomology 59: 95–117.

Cann RL, Stoneking M and Wilson AC (1987) Mitochondrial DNA and human evolution. Nature 325 (3): 31–36.

Coissac E, Hollingsworth PM, Lavergne S and Taberlet P (2016) From barcodes to genomes: extending the concept of DNA barcoding. Molecular Ecology 25 (7): 1423–1428.

Corlett RT (2017) A bigger toolbox: biotechnology in biodiversity conservation. Trends in Biotechnology 35 (1): 55–65.

Crampton‐Platt A, Yu DW, Zhou X and Vogler AP (2016) Mitochondrial metagenomics: letting the genes out of the bottle. GigaScience 5: 1–15.

DeSalle R, Egan MG and Siddall M (2005) The unholy trinity: taxonomy, species delimitation and DNA barcoding. Philosophical Transactions of the Royal Society, B: Biological Sciences 360 (1462): 1905–1916.

DeSalle R (2016) Comments on Smith (2015). ‘The past, present and future of mitochondrial genomics: have we sequenced enough mtDNAs’. Briefings in Functional Genomics 2015: elv052.

Desalle R, Schierwater B and Hadrys H (2017) MtDNA: the small workhorse of evolutionary studies. Frontiers in Bioscience (Landmark Edition) 22: 873.

da Fonseca RR, Johnson WE, O'Brien SJ, Ramos MJ and Antunes A (2008) The adaptive evolution of the mammalian mitochondrial genome. BMC Genomics 9: 119.

Garvin MR, Bielawski JP, Sazanov LA and Gharrett AJ (2015) Review and meta‐analysis of natural selection in mitochondrial complex I in metazoans. Journal of Zoological Systematics and Evolutionary Research 53 (1): 1–17.

Goldstein PZ and DeSalle R (2011) Integrating DNA barcode data and taxonomic practice: determination, discovery, and description. Bioessays 33: 135–147.

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

Haig D (2016) Intracellular evolution of mitochondrial DNA (mtDNA) and the tragedy of the cytoplasmic commons. BioEssays 38 (6): 549–555.

Hajibabaei M, Baird DJ, Fahner NA, Beiko R and Brian Golding G (2016) A new way to contemplate Darwin's tangled bank: how DNA barcodes are reconnecting biodiversity science and biomonitoring. Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences 371 (1702): 20150330.

Hebert PDN, Cywinska A and Ball SL (2003) Biological identifications through DNA barcodes. Proceedings of the Royal Society of London B: Biological Sciences 270 (1512): 313–321.

Hill GE (2017) The mitonuclear compatibility species concept. The Auk 134 (2): 393–409.

Hoffmann C, Schubert G and Calvignac‐Spencer S (2016) Aquatic biodiversity assessment for the lazy. Molecular Ecology 25 (4): 846–848.

Holmes MW, Hammond TT, Wogan GOU, et al. (2016) Natural history collections as windows on evolutionary processes. Molecular Ecology 25 (4): 864–881.

Jacobsen MW, da Fonseca RR, Bernatchez L and Hansen MM (2016) Comparative analysis of complete mitochondrial genomes suggests that relaxed purifying selection is driving high nonsynonymous evolutionary rate of the NADH2 gene in whitefish (Coregonus ssp.). Molecular Phylogenetics and Evolution 95: 161–170.

James JE, Piganeau G and Eyre‐Walker A (2016) The rate of adaptive evolution in animal mitochondria. Molecular Ecology 25: 67–78.

Kocher TD, Thomas WK, Meyer A, et al. (1989) Dynamics of mitochondrial DNA evolution in animals: amplification and sequencing with conserved primers. Proceedings of the National Academy of Sciences 86 (16): 6196–6200.

Kolesnikov AA and Gerasimov ES (2012) Diversity of mitochondrial genome organization. Biochemistry (Moscow) 77 (13): 1424–1435.

Kolokotronis S‐O, Foox J, Rosenfeld JA, et al. (2016) The mitogenome of the bed bug Cimex lectularius (Hemiptera: Cimicidae). Mitochondrial DNA Part B, Resources 1 (1): 425–427.

Latorre‐Pellicer A, Moreno‐Loshuertos R, Lechuga‐Vieco AV, et al. (2016) Mitochondrial and nuclear DNA matching shapes metabolism and healthy ageing. Nature 535 (7613): 561–565.

Lavrov DV and Pett W (2016) Animal mitochondrial DNA as we do not know it: mt‐genome organization and evolution in nonbilaterian lineages. Genome Biology and Evolution 8 (9): 2896–2913.

Lopes CM, Sasso T, Valentini A, et al. (2017) eDNA metabarcoding: a promising method for anuran surveys in highly diverse tropical forests. Molecular Ecology Resources.

Meiklejohn CD, Holmbeck MA, Siddiq MA, et al. (2013) An Incompatibility between a mitochondrial tRNA and its nuclear‐encoded tRNA synthetase compromises development and fitness in Drosophila. PLoS Genetics 9 (1): e1003238.

Nielsen R, Akey JM, Jakobsson M, et al. (2017) Tracing the peopling of the world through genomics. Nature 541 (7637): 302–310.

Pagliarini DJ, Calvo SE, Chang B, et al. (2008) A mitochondrial protein compendium elucidates complex I disease biology. Cell 134 (1): 112–123.

Pittis AA and Gabaldón T (2016) Late acquisition of mitochondria by a host with chimaeric prokaryotic ancestry. Nature 531: 101–104.

Rosenfeld JA, Reeves D, Brugler MR, et al. (2016) Genome assembly and geospatial phylogenomics of the bed bug Cimex lectularius. Nature Communications 7: 10164.

Ruiz‐Pesini E, Mishmar D, Brandon M, Procaccio V and Wallace DC (2004) Effects of purifying and adaptive selection on regional variation in human mtDNA. Science 303 (5655): 223–226.

Sankoff D, Leduc G, Antoine N, et al. (1992) Gene order comparisons for phylogenetic inference: evolution of the mitochondrial genome. Proceedings of the National Academy of Sciences 89: 6575–6579.

Slatkin M and Racimo F (2016) Ancient DNA and human history. Proceedings of the National Academy of Sciences 113 (23): 6380–6387.

Sunnucks P, Morales HE, Lamb AM, Pavlova A and Greening C (2017) Integrative approaches for studying mitochondrial and nuclear genome co‐evolution in oxidative phosphorylation. Frontiers in Genetics 8: 25.

Tang MT, Meng G, Yang S, et al. (2014) Multiplex sequencing of pooled mitochondrial genomes – a crucial step toward biodiversity analysis using mito‐metagenomics. Nucleic Acids Research 42: e166.

Timmermans JTNM, Viberg C, Martin G, Hopkins K and Vogler AP (2016) Rapid assembly of taxonomically validated mitochondrial genomes from historical insect collections. Biological Journal of the Linnean Society 117: 83–95.

Valentini PT, Miaud C, Civade R, Herder J, et al. (2016) Next‐generation monitoring of aquatic biodiversity using environmental DNA metabarcoding. Molecular Ecology 25: 929–942.

Van Oven M and Kayser M (2009) Updated comprehensive phylogenetic tree of global human mitochondrial DNA variation. Human Mutation 30 (2): E386–E394.

Further Reading

Boore JL and Brown WM (1998) Big trees from little genomes: mitochondrial gene order as a phylogenetic tool. Current Opinion in Genetics & Development 8: 668–674.

Consuegra S, John E, Verspoor E and Garcia De Leaniz C (2015) Patterns of natural selection acting on the mitochondrial genome of a locally adapted fish species. Genetics Selection Evolution 47 (1): 58.

Gillett CPDT, Crampton‐Platt A, Timmermans MJTN, et al. (2014) Bulk de novo mitogenome assembly from pooled total DNA elucidates the phylogeny of weevils (Coleoptera: Curculionoidea). Molecular Biology and Evolution 31 (8): 2223–2237.

Jones MR and Good JM (2016) Targeted capture in evolutionary and ecological genomics. Molecular Ecology 25 (1): 185–202.

Linard B, Crampton‐Platt A, Gillett CP, Timmermans MJ and Vogler AP (2015) Metagenome skimming of insect specimen pools: potential for comparative genomics. Genome Biology and Evolution 7: 1474–1489.

Satoh TP, Miya M, Mabuchi K and Nishida M (2016) Structure and variation of the mitochondrial genome of fishes. BMC Genomics 17 (1): 719.

Simon S and Hadrys H (2013) A comparative analysis of complete mitochondrial genomes among hexapoda. Molecular Phylogenetics and Evolution 69 (2): 393–403.

Strohm JHT, Gwiazdowski RA and Hanner R (2015) Fast fish face fewer mitochondrial mutations: patterns of dN/dS across fish mitogenomes. Gene 572 (1): 27–34.

Tang MT, Meng G, Yang S, et al. (2014) Multiplex sequencing of pooled mitochondrial genomes – a crucial step toward biodiversity analysis using mito‐metagenomics. Nucleic Acids Research 42: e166.

Vossen RHAM and Buermans HPJ (2017) Full‐length mitochondrial‐DNA sequencing on the PacBio RSII. Genotyping: Methods and Protocols 1492: 179–184.

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DeSalle, Rob, and Hadrys, Heike(Jul 2017) Evolutionary Biology and Mitochondrial Genomics: 50 000 Mitochondrial DNA Genomes and Counting. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0027270]