Presentation on theme: "Organelle genomes Small but essential genomes Multiple organelles per cell; multiple genomes per organelle (20 – 20,000 genomes per cell, depending on."— Presentation transcript:
Organelle genomes Small but essential genomes Multiple organelles per cell; multiple genomes per organelle (20 – 20,000 genomes per cell, depending on cell type) Organized in nucleo-protein complexes called nucleoids Non-Mendelian inheritance; usually but not always maternally inherited Encode necessary but insufficient information to elaborate a fully functional organelle Many nuclear gene products required for organelle function Considerable cross-talk between nuclear and organelle genetic systems
Group II introns, which are widely believed to be the progenitors of the nuclear splicing machinery (the spliceosome) and its substrates, comprise a large ribozyme (catalytic RNA) and the coding sequence of a reverse transcriptase. Group II introns are found in mitochondrial, chloroplast and bacterial genomes and a majority of them behave as retrotransposons.
HUMAN NUCLEAR GENOME 24 chromosomes (haploid) 3200 Mbp 30,000 genes Mitochondrial genome 16569 bp 37 genes Human genome = nuclear genome + mitochondrial genome
1-10 m small Mitochondria are present in the cytoplasm of all eukaryote cells of animals and higher plants and also in some microorganisms (algae, fungi, protozoa).
Mitochondrial Genome Small circular genome >1000 copies/ cell 16569 bp44% G+C H- StrandGuanines L- StrandCytosines D- Loop7S DNA
Mitochondrion plays a role in: Energy production Oxidative phosphorilation (OXPHOS) Maintaining the intracellular homeostasis Protecting the rest of the cell from reactive oxygen species (ROS) Apoptosis important development and disease
Mitochondria-the point of no return-to live or to die casp9 Bcl2 Apaf1 ATP Caspase 3 Apoptosis AIF substrates AIF Nuclear apoptosis Smac/ Diablo XIAP Pro-caspase 3
Genome Structure The mitochondrial genome is a circle, 16.6 kb of DNA. A typical bacterial genome is 2-4 Mbp. The two strands are notably different in base composition, leading to one strand being “heavy” (the H strand) and the other light (the L strand). Both strands encode genes, although more are on the H strand. A short region (1121 bp), the D loop (D = “displacement”), is a DNA triple helix: there are 2 overlapping copies of the H strand there. The D loop is also the site where most of replication and transcription is controlled. Genes are tightly packed, with almost no non-coding DNA outside of the D loop. In one case, two genes overlap: they share 43 bp, using different reading frames. Human mitochondrial genes contain no introns, although introns are found in the mitochondria of other groups (plants, for instance).
The Human Mitochondrial Genome Circular ~ 16 kb (some plants ~100 kb!) Crowded (~40 genes) 13 genes involved in oxidative phosphorylation + other genes (DNA pol, rDNAs, tRNAs) Most proteins in mitochondria are imported from cytoplasm 100,000 copies of mitochondrial DNA in ovum 2 - 10 copies/mitochondrion
Organization of the human genome Limited autonomy of mt genomes mt encodednuclear NADH dehydrog 7 subunits>41 subunits Succinate CoQ red0 subunits4 subunits Cytochrome b-c1 comp1 subunit10 subunits Cytochrome C oxidase 3 subunits10 subunits ATP synthase complex2 subunits14 subunits tRNA components22 tRNAsnone rRNA components 2 componentsnone Ribosomal proteins none ~80 Other mt proteinsnonemtDNA pol, RNA pol etc.
The Human Mitochondrial Genome expression unlike nucleus genome… Transcription controlled by nuclear proteins: 3 promoters- * H1: H-strand; complete transcription of one strand of mtDNA * L: L-strand; complete transcription of light strand of mtDNA * H2: Synthesis of 2 rRNAs Transcripts then procesed into individual genes prior to translation
Mitochondrial Genetic code is somewhat different… Human Mito Standard AGA Ter Arg AGG Ter Arg AUA, AUU Met Ile UGA Trp Ter Plastid genetic code: GUG, UUG, AUU, CUG can initiate translation UGA encodes trp at low efficiency in E. coli
Mitochondrial inheritance pattern - uniparental maternal in animals Paternal inheritance in gymnosperms, some angiosperms
Endosymbiont Hypothesis endosymbiont hypothesis: originally proposed in 1883 by Andreas Schimper, but extended by Lynn Margulis in the 1980s. Mitochondrial ribosomal RNA genes and other genes show that the original organism was in the alpha-proteobacterial family (similar to nitrogen-fixing bacteria) Evidence: – mitochondria have their own DNA (circular) – the inner membrane is more similar to prokaryotic membranes than to eukaryotic. By the hypothesis, the inner membrane was the original prokaryotic membrane and the outer membrane was from the primitive eukaryote that swallowed it. – mitochondria make their own ribosomes, which are of the prokaryotic 70S type, not the eukaryotic 80S type. – mitochondria are sensitive to many bacterial inhibitors that don’t affect the rest of the eukaryotic cell, such as streptomycin, chloramphenicol, rifampicin. – mitochondrial protein synthesis starts with N-formyl methionine, as in the bacteria but unlike eukaryotes. Most of the original bacterial genes have migrated into the nucleus. Eukaryotes that lack mitochondria generally have some mitochondrial genes in their nucleus, evidence that their ancestors had mitochondria that were lost during evolution.