Mitochondrial DNA Replication
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This presentation deals with DNA replication in mamalian mitochondria. Mammalian mtDNA is replicated by proteins distinct from those used for nuclear DNA replication. According to the strand displacement model, replication is initiated from two distinct origins, OH and OL.
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Mitochondrial DNA Replication
- 1. GARRY D. LASAGA MITOCHONDRIAL DNA REPLICATION 1 Compiled by: GARRY D. LASAGA
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- 5. Figure 14-3 Essential Cell Biology (© Garland Science 2010) 02/03/2018 5
- 6. Figure 3. Transmission electron microscopy images on mitochondria 02/03/2018 6
- 8. Mitochondrial DNA mtDNA is double stranded circular DNA molecule mt DNA contain 37 genes for normal mitochondrial function 13 genes make enzymes involved in oxidative phosphorylation 02/03/2018 8
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- 12. Maternal Inheritance of mtDNA mtDNA is transmitted through the female egg mtDNA is nonrecombinant During fertilization, the sperm only contributes its nucleus (23 chromosomes) Mitochondria of the sperm cell are located at the mitochondrial sheath which is destroyed upon fertilization (there are some recent studies that oppose this claim). 02/03/2018 12
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- 14. The Mitochondrial Genome 16,569 base pairs (bp) in length (16-18 kbp) Encodes for 37 genes, 13 proteins, 22 tRNAs, and 2 rRNAs Two general regions: Coding region Control region 02/03/2018 14
- 15. The Mitochondrial Genome Mitochondrial DNA is maternally inherited in most species(Gyllesten et al., 1991) It does not recombine (Hayashi et al., 1985) Though some evidence of recombination events has recently been reported (Eyre-Walker et al., 1999; Hagelberg et al., 1999) 02/03/2018 15
- 16. NUCLEAR DNA MITOCHONDRIAL DNA Found in the nucleus Found in the mitochondria 2 sets of 23 chromosomes Each mitochondria may have several copies of the single mtDNA molecule Maternal and paternal Maternal only Can “discriminate between individuals of the same maternal lineage” Cannot “discriminate between individuals of the same maternal lineage” 02/03/2018 16
- 17. NUCLEAR DNA MITOCHONDRIAL DNA Double helix Circular DNA is packed into chromatin DNA is not packed into chromosome 02/03/2018 17
- 18. D-loop region F PTA S 1 2 3 LS P HS P O H 02/03/2018 18
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Editor's Notes
- Mitochondria are subcellular organelles found in most eukaryotic cells. These structures are often referred to as the ”powerhouses” of the cell since they produce most of the adensosine triphosphate (ATP) required in the cell. To this end, mitochondria contain essential enzyme systems involved in energy metabolism, such as the respiratory chain, the citric acid cycle, and the enzymes required for β-oxidation. Mitochondria also contain their own genome present in multiple copies. Genome: genetic material in a cell or organism. The mitochondrial genome is separate and distinct from that of the nucleus. The mitochondrial DNA (mtDNA) is a small circular molecule that codes for some proteins in the respiratory chain and RNA molecules involved in translation of these proteins inside mitochondria. Mitochondria have their own DNA and express their genes to produce proteins active in the electron transport chain. However, most of the proteins they need are encoded in the nucleus of the cell. They need to import most of their proteins to function.
- When studying the mitochondrion using electron microscopy it became evident that the mitochondrion has two membranes: one outer membrane and one inner membrane that was convoluted and folded into cristae.
- The number and morphology of the cristae has been suggested to reflect the energy demand of the cell since highly folded cristae are found in cell types with high respiration such as muscle cells and neurons.
- The morphology of the mitochondrion varies between different cell types and organisms. In some cells mitochondria have the shape of a bean whereas in other cells they form elongated tubules. A. Tubular-shaped cristae from hamster adrenal cortex (upper) and from Singh amoeba (lower). B. Mitochondria from adipose cells from little brown fat. Singh amoeba (lower) B. Mitochondria from adipose cells from Myotis lucifugus (little brown bat). The cristae are seen in transverse. 11434 (A) and 11428 (B)).
- The mitochondrial DNA is typically less than 1% of an animal cell’s DNA population. Mitochondria also contain their own genome present in multiple copies. Genome: genetic material in a cell or organism. The mitochondrial genome is separate and distinct from that of the nucleus. The mitochondrial DNA (mtDNA) is a small circular molecule that codes for some proteins in the respiratory chain and RNA molecules involved in translation of these proteins inside mitochondria. Mitochondria have their own DNA and express their genes to produce proteins active in the electron transport chain. However, most of the proteins they need are encoded in the nucleus of the cell. They need to import most of their proteins to function.
- Haploid refers to the reduced number of chromosomes in the ovum and sperm – half the (diploid) number in the somatic cells. In humans, there are about 20,000 to 25,000 protein coding genes and the mitochondrial DNA only contains 37 of those genes.
- A schematic presentation of a mitochondrial genome (human). It is a closes circular molecule. It has 2 strands that can be separated on a cesium chloride gradient. One of the strands is named heavy strand (H-strand), whereas the other strand is named light strand (L-strand). The H-strand is the template for transcription of the majority of genes, whereas the L-strand is the template for ND6 mRNA and eight tRNAs . SHAPE: double helix vs circular
- Mitochondria use a genetic code that differs from the “standard” genetic code. As an example UGA, which is a stop codon in most organisms, codes for tryphtophan in vertebrate mitochondria.
- It is said that we inherit mitochondrial DNA only from our mothers. In other words, the mtDNA can be passed down from mothers to both sons and daughters, but sons cannot pass along the mothers mtDNA to their children. NONRECOMBINANT – it does not combine with any other DNA so that it is passed down virtually unchanged through the direct maternal line over the generations.
- Because of its cytoplasmic location in eukaryotes, mtDNA does not undergo meiosis and there is normally no crossing-over, hence there is no opportunity for introgression of the father’s mtDNA. Introgression: entry or introduction of a gene from one gene complex into another (hybridization).
- CODING REGION: responsible for the production of various biological molecules involved in "cellular respiration“ CONTROL REGION: responsible for the regulation of the mtDNA molecule
- One’s mtDNA is nearly identical to the mtDNA of your straight line maternal ancestor who lived thousand of years ago, and it is also identical to thousands of people living today.
- Human mtDNA contains only one longer region, which is non-coding, and it is called the non-coding region or the control region. This region contains the regulatory elements the origin of H-strand replication (OH) and the transcriptional promoters. The signature form of mammalian mtDNA is the displacement loop (D-loop) molecule. The D-loop is defined as a three-stranded structure with the nascent leading H strand defining the origin of leading-strand replication (OH).
- Replication starts at a specific origin in the circular duplex DNA. But initially only one of the two parental strands (the H strand in mammalian mitochondrial DNA) is used as a template for synthesis of a new strand. Synthesis proceeds for only a short distance, displacing the original partner (L) strand, which remains single-stranded, as illustrated in Figure. The condition of this region gives rise to its name as the displacement or D loop