Mitochondrial genetics

mtDNA is the only source of DNA outside the nucleus in mammals and has a number of distinct properties. The human mitochondrial genome is a double-stranded circular DNA molecule, 16,569 bp in length, accounting for approximately 1% of total cellular DNA. The complete sequence was determined in 1981 (Anderson et al., 1981) (Cambridge Reference Sequence - CRS) and was re-sequenced in 1999 (Andrews et al., 1999) enabling the correction of some sequence errors and common polymorphic variants. The revised Cambridge Reference Sequence (rCRS) is available through the MITOMAP web site (MITOMAP, 2005). Expression of almost the complete genome is required for respiratory chain function, in comparison to only 7% of the nuclear genome being expressed at any one time. mtDNA has a different codon usage, is strictly maternally inherited and undergoes little if any intermolecular recombination. mtDNA encodes 37 genes; 13 essential polypeptides of the mitochondrial respiratory chain as well as 22 transfer RNA (tRNA) and 2 ribosomal RNA (rRNA) genes (Figure 11.1) that are

12s RNA

16s RNA

M ND2

12s RNA

16s RNA

M ND2

R ND3

CQ2 KATPase8

ATPase6

Complex I genes - NADH dehydrogenase

Complex III genes - ubiquinol cytochrome c oxidoreductase

Complex IV genes - ATP synthase

Complex V genes - ATP synthase

Transfer RNA genes

Ribosomal RNA genes

Noncoding displacement loop

R ND3

CQ2 KATPase8

ATPase6

Complex I genes - NADH dehydrogenase

Complex III genes - ubiquinol cytochrome c oxidoreductase

Complex IV genes - ATP synthase

Complex V genes - ATP synthase

Transfer RNA genes

Ribosomal RNA genes

Noncoding displacement loop

Figure 11.1

Sequence arrangement of the human mitochondrial genome. Genes are coded as the differently shaded inset. OH and OL are the origins of replication for the heavy and light strands respectively. PH and PL are the promoters for the heavy and light strands respectively.

essential for intra-mitochondrial translation and transcription. The mitochondrial genome contains no introns and is so compact that there are regions of gene overlap. The displacement loop (D-loop), approximately 1.1 kb in length, is not directly involved in protein synthesis but plays a crucial role in regulating translation and transcription of the mtDNA molecule.

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