Mitochondrial Genome

Abstract

Mitochondria are cytoplasmic organelles present in all eukaryotic cells that are able to respire. They possess their own genetic system whose size and organisation are quite variable in plants, protists and fungi. A certain degree of structural variability is observed also in Metazoa. In human and all vertebrates, mitochondrial deoxyribonucleic acid (mtDNA) is rather small (about 17 kb) but constant as genetic content and organisation. It consists of two ribosomal ribonucleic acid (RNA) genes, 13 proteinā€coding genes and 22 transfer RNAs. All other mitochondrial products are coded by nuclear DNA and transported into the mitochondrion. Mitochondrial genetic system has a uniparental, usually maternal, way of inheritance, and it is present in cell in a multicopy state. mtDNA replication, transcription and translation are also very peculiar. Evolutionary origin of mitochondria has been described through the endosymbiotic theory.

Key Concepts

  • Mitochondria are eukaryotic cell organelles with their own genome.
  • Mitochondrial genome shows great structural variability in most eukaryotic taxa but is quite stable for content and organisation in Metazoans.
  • mtDNA has a small size with a poor gene content.
  • Two types of genes are encoded by mtDNA: genes for protein synthesis machinery and genes for respiratory chain subunits, fundamental for cell energy production.
  • The mitochondrial genome has bacterial origin, with several peculiar features about its replication and expression.
  • mtDNA is a multicopy genome that is uniparentally, usually maternal, transmitted and does not undergo recombination.
  • Evolution of mtDNA (within Metazoa) is lineage specific.

Keywords: organelle DNA; oxidative phosphorylation; energy production; D loop; endosymbiosis; unidirectional inheritance; recombination; selection; mutation; phylogenetic inference

Figure 1. Schematic representation of the mitochondrion with details of the inner membrane and its respiratory complexes (I–V). Mitochondria are formed by two membranes, an outer membrane having mainly permeability properties and an inner membrane where electron transport and oxidative phosphorylation occur. The inner space, called matrix, contains metabolic enzymes, the mitochondrial DNA (deoxyribonucleic acid), and the genetic apparatus for its replication and expression. The electron (e) flux through the respiratory complexes results in a drop in the free energy, which is used to pump protons (H+) from the matrix to the intermembrane space. The energy conserved into this proton gradient is used to promote adenosine 5′‐triphosphate (ATP) synthesis by ATP synthase through the inversion of proton flux from intermembrane space to matrix. Abbreviations: ADP, adenosine 5′‐diphosphate; NAD+, oxidised form of nicotinamide–adenine dinucleotide; NADH, reduced form of nicotinamide–adenine dinucleotide and QU, ubiquinone.
Figure 2. Organisation of human mitochondrial DNA. The two strands are called heavy (H) and light (L) according to their isopycnic sedimentation in a caesium chloride gradient. Gene distribution between the two strands and the main regulatory regions is indicated. The protein‐coding genes are ATP6, ATP8 and ATPase subunits; CO I, II, III and cytochrome c oxidase subunits; Cytb, cytochrome b; 1, 2, 3, 4, 4L, 5, 6 and NADH dehydrogenase subunits; 12S, 16S rRNAs and small and large ribosomal subunits RNA; A, alanine; C, cysteine; D, aspartic acid; E, glutamic acid; F, phenylalanine; G, glycine; H, histidine; I, isoleucine; K, lysine; L, leucine; M, methionine; N, asparagine; OL , L strand replication origin; OH, H strand replication origin; P, proline; Q, glutamine; R, arginine; S, serine; T, threonine; V, valine; W, tryptophan and Y, tyrosine transfer RNA (ribonucleic acid) genes. In the expanded D‐loop region, CSB, conserved sequence box; ETAS, extended termination‐associated sequences; HSP, H strand promoter; LR and SR, short and long repeats; LSP, L strand promoter; the conserved central domain (black bar), the RNA primer (grey) and the RNA/DNA transition are indicated.
Figure 3. Schematic representation of replication and transcription models of the human mitochondrial genome. (A) Current models of mammalian mtDNA replication: the strand displacement (a, red), the RNA incorporated throughout the lagging strand (RITOLS) (b, blue) and the leading and lagging strand‐coupled (c, green) models. Coloured lines indicate new synthesised strands. Black lines indicate parental DNA. In all models, the sites OH and OL are represented as reference points, although these sites are primarily important for the strand‐displacement model. Arrows associated with replicating mtDNA indicate the 5′–3′ direction of nucleic acid synthesis; continuous and dashed lines represent DNA and RNA, respectively. Black arrowheads indicate the number and directionality of replication forks generated at the origin, according to each model. (B) Model of mammalian mtDNA transcription. Are shown the light strand promoter (LSP) and pre‐mRNA generated from that promoter (red); the heavy strand promoter 1 (HSP1) and its pre‐mRNA (yellow); the heavy strand promoter 2 (HSP2) and its pre‐mRNA (green); and the location of first‐strand DNA replication initiation (OH), which is primed from LSP‐derived transcripts.
Figure 4. Graphical representation of GC skew and GC content calculated on the whole mitochondrial genome in five mammalian orders and Homo sapiens.
Figure 5. Nucleotide substitution rate of the different mitochondrial DNA functional regions in mammals.
Figure 6. Maternal inheritance of mitochondrial DNA. The small black arrow indicates the common ancestor of the whole lineage derived from it.
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Saccone, Cecilia, and Gadaleta, Gemma(Jan 2017) Mitochondrial Genome. In: eLS. John Wiley & Sons Ltd, Chichester. http://www.els.net [doi: 10.1002/9780470015902.a0005069.pub3]