Unit 05 Part 3

Genetic Systems
- Mitochondrial and chloroplast genetic systems resemble prokaryotic systems.
- Mitochondria and chloroplasts have exported most of their genes to the nucleus over time.
- Mitochondria exhibit relaxed codon usage; variant genetic code possible.
- Chloroplasts share significant similarities with bacteria.
- Organellar genes are maternally inherited in plants and animals.

Two distinct genetic systems exist in cells:
- Nuclear DNA: Approximately 1,000 genes; transcribed, translated, and imported via TOMs and TIMS.
- Mitochondrial DNA (mtDNA): Expressed within the mitochondrion; all necessary protein machinery for its transcription and translation is encoded by nuclear DNA.

Origin of Mitochondria: Result of a symbiotic relationship between an archaeon and aerobic bacterium for ATP production.
Chloroplast Origin: Arose via endocytosis of oxygen-producing cyanobacterium after divergence of plant and animal lineages.
Genetic Similarities:
- Chloroplast DNA (cpDNA) has similarities to prokaryotic DNA and expression systems.
- Mitochondrial DNA (mtDNA) exhibits fewer similarities, particularly regarding ribosomes.
Antibiotic Sensitivity: Chloroplasts and mitochondria display similar sensitivity to specific antibiotics, including chloramphenicol and tetracycline.
Translation Characteristics:
- Initiation with N-formylmethionine.
- Polycistronic messages with tRNAs acting as punctuation.
- PolyA tails added post-transcriptionally.

Proponent: Lynn Margulis (1938-2011).
- Advocated for the endosymbiotic origin of mitochondria and chloroplasts.
- Initial proposal faced rejection by 15 journals but is now recognized as a pivotal development in 20th-century biology.
- Advocate of bacteria’s essential role in Earth’s biosphere.

Overview:
- Human mtDNA is approximately 16.5 kb and contains 37 genes (13 protein-coding, 22 tRNAs, 2 rRNAs).
- Number of mitochondria per cell varies from 1 to thousands; typically 1-10 copies of mtDNA per organelle.
- mtDNA resides adjacent to the inner mitochondrial membrane (IMM).

Most of the original organellar genome has been integrated into nuclear DNA across eukaryotic evolution.
Essential adaptations needed for nuclear transcription and cytoplasmic translation.
Maintenance and expression of mtDNA require over 90 proteins, an area under active research.

Dense Gene Packaging: Human mtDNA lacks introns (unlike yeast mtDNA).
Relaxed Codon Usage: Uses 22 tRNAs versus 30 for cytosolic translation.
Variant Genetic Code: Example: A codon typically signaling STOP (UGA) acts as Tryptophan in animal mtDNA.
Increased Mutation Rate: Approximately 10x higher than nuclear DNA due to limited DNA repair mechanisms.
Vulnerability: Exposure to reactive oxygen species (ROS) contributes to mutations.
Replication: Occurs independently of the cell cycle.

Relaxation in the control of mtDNA replication noted in yeast and mammals.
Possible replication of single mitochondrial DNA units in each cell cycle.
Presence of heterogeneous mtDNA populations within cells leading to heteroplasmy, where not all mtDNA is identical.

OXPHOS machinery shows interplay between nuclear and mitochondrial genomes:
- Contributions from mtDNA include components of various complexes I, III, IV, V relative to their total subunit composition.

Types of Mutation Sources:
- Mutations in mitochondrial DNA can lead to over 200 pathogenic conditions.
  - Examples: MELAS, MERRF, KSS, LHON (maternal inheritance).
- Mutations in nuclear DNA also contribute (autosomal characteristics).
  - Examples: Leigh syndrome, Friedrich ataxia.
- Reports of 'secondary' OXPHOS dysfunction related to neurological disorders such as Alzheimer’s disease.